1. A case control study of carcinoma of the ovary
Abstract
“There is increased concern over the apparent rise in incidence of patients with carcinoma of the ovary, particularly in older women. In an attempt to identify aetiological factors 300 women with cancer of the ovary diagnosed at laparatomy were studied. A questionnaire was administered to these women (Group A) and to two control groups matched by age. The first control group (Group B) comprised patients in a gynaecological ward and the second (Group C) comprised women on the lists of general practitioners living in the same areas as the index cases. Differences were shown in the obstetric history of the three groups. Fewer of the women in Group A had married and fewer had ever been pregnant and the family size was smaller. Significantly fewer of them recollected an attack of mumps, measles, or rubella. In all, only 81 of the whole series of 900 had used oral contraceptives, 19 of Group A and 31 in each of the control groups, a statistically significant deficiency. These findings support those of other investigations and suggest lines of further inquiry.”
Link
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC479015/
Citation
Newhouse, M. L., R. M. Pearson, J. M. Fullerton, E. A. Boesen, and H. S. Shannon. "A Case Control Study of Carcinoma of the Ovary." Journal of Epidemiology & Community Health 31.3 (1977): 148-53.
“There is increased concern over the apparent rise in incidence of patients with carcinoma of the ovary, particularly in older women. In an attempt to identify aetiological factors 300 women with cancer of the ovary diagnosed at laparatomy were studied. A questionnaire was administered to these women (Group A) and to two control groups matched by age. The first control group (Group B) comprised patients in a gynaecological ward and the second (Group C) comprised women on the lists of general practitioners living in the same areas as the index cases. Differences were shown in the obstetric history of the three groups. Fewer of the women in Group A had married and fewer had ever been pregnant and the family size was smaller. Significantly fewer of them recollected an attack of mumps, measles, or rubella. In all, only 81 of the whole series of 900 had used oral contraceptives, 19 of Group A and 31 in each of the control groups, a statistically significant deficiency. These findings support those of other investigations and suggest lines of further inquiry.”
Link
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC479015/
Citation
Newhouse, M. L., R. M. Pearson, J. M. Fullerton, E. A. Boesen, and H. S. Shannon. "A Case Control Study of Carcinoma of the Ovary." Journal of Epidemiology & Community Health 31.3 (1977): 148-53.
2. Varicella Zoster Virus Infection of Malignant Glioma Cell Cultures: A New Candidate for Oncolytic Virotherapy?
Abstract
“Background: Glioblastoma multiforme is a highly aggressive tumor with a median survival of 14 months despite all standard therapies. Focusing on alternative treatment strategies, we evaluated the oncolytic potential of varicella zoster virus (VZV) in malignant glioma cell cultures. Materials and Methods: Replication of wildtype and mutant VZV was comparatively analyzed in glioma cell lines (U87, U251 and U373) and in primary malignant glioma cells (n=10) in vitro by infectious foci assay, immunofluorescence microscopy and western blot analysis. Additionally, the tumor-targeting potential of VZV-infected human mesenchymal stem cells was evaluated. Results: VZV replicated efficiently in all the glioma cells studied here followed by rapid oncolysis in vitro. The attenuated vaccine VZV mutant rOKA/ORF63rev[T171] exhibited most efficient replication. Human mesenchymal stem cells were found suitable for targeting VZV to sites of tumor growth. Conclusion: VZV exhibits an intrinsic oncolytic potential in malignant glioma cell cultures and might be a novel candidate for virotherapy in glioblastoma multiforme.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/22493342
Citation
Auffinger, Brenda, Atique U. Ahmed, and Maciej S. Lesniak. "Oncolytic Virotherapy for Malignant Glioma: Translating Laboratory Insights into Clinical Practice." Front. Oncol. Frontiers in Oncology 3 (2013)
“Background: Glioblastoma multiforme is a highly aggressive tumor with a median survival of 14 months despite all standard therapies. Focusing on alternative treatment strategies, we evaluated the oncolytic potential of varicella zoster virus (VZV) in malignant glioma cell cultures. Materials and Methods: Replication of wildtype and mutant VZV was comparatively analyzed in glioma cell lines (U87, U251 and U373) and in primary malignant glioma cells (n=10) in vitro by infectious foci assay, immunofluorescence microscopy and western blot analysis. Additionally, the tumor-targeting potential of VZV-infected human mesenchymal stem cells was evaluated. Results: VZV replicated efficiently in all the glioma cells studied here followed by rapid oncolysis in vitro. The attenuated vaccine VZV mutant rOKA/ORF63rev[T171] exhibited most efficient replication. Human mesenchymal stem cells were found suitable for targeting VZV to sites of tumor growth. Conclusion: VZV exhibits an intrinsic oncolytic potential in malignant glioma cell cultures and might be a novel candidate for virotherapy in glioblastoma multiforme.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/22493342
Citation
Auffinger, Brenda, Atique U. Ahmed, and Maciej S. Lesniak. "Oncolytic Virotherapy for Malignant Glioma: Translating Laboratory Insights into Clinical Practice." Front. Oncol. Frontiers in Oncology 3 (2013)
3. ROLE OF MEDICAL HISTORY IN BRAIN TUMOUR DEVELOPMENT. RESULTS FROM THE INTERNATIONAL ADULT BRAIN TUMOUR STUDY
Abstract
“In an international population-based case-control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age- and gender-matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR 5 6.55, 95% CI 3.40–12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti-epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR 5 0.59, 95% CI 0.49–0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR 5 0.72, 95% CI 0.61–0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/10389745
Citation
Schlehofer, Brigitte, Maria Blettner, Susan Preston-Martin, Dorothea Niehoff, Jürgen Wahrendorf, Annie Arslan, Anders Ahlbom, Won N. Choi, Graham G. Giles, Geoffrey R. Howe, Julian Little, Francois Ménégoz, and Philip Ryan. "Role of Medical History in Brain Tumour Development. Results from the International Adult Brain Tumour Study." International Journal of Cancer 82.2 (1999): 155.
“In an international population-based case-control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age- and gender-matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR 5 6.55, 95% CI 3.40–12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti-epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR 5 0.59, 95% CI 0.49–0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR 5 0.72, 95% CI 0.61–0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/10389745
Citation
Schlehofer, Brigitte, Maria Blettner, Susan Preston-Martin, Dorothea Niehoff, Jürgen Wahrendorf, Annie Arslan, Anders Ahlbom, Won N. Choi, Graham G. Giles, Geoffrey R. Howe, Julian Little, Francois Ménégoz, and Philip Ryan. "Role of Medical History in Brain Tumour Development. Results from the International Adult Brain Tumour Study." International Journal of Cancer 82.2 (1999): 155.
4. Risk of Childhood Leukemia Associated with Vaccination, Infection, and Medication Use in Childhood
Abstract
“Current hypotheses consonant with the peak in leukemia incidence in early childhood point to an infectious etiology. The authors examined the effect of postnatal exposures predicted to affect early immune functioning, including childhood vaccinations, illness, medication use, and breastfeeding patterns. Children 0–15 years of age diagnosed with leukemia from 1990 to 1994 and resident within principal cities across Canada were eligible for inclusion. Through pediatric oncology centers and population-based cancer registries, 399 cases were ascertained at the time of diagnosis. For each participating case, an age-, gender-, and area-matched control was randomly selected from government health insurance rolls. Risk factor information was obtained through personal interviews with each child’s parents or guardians. Conditional logistic regression was used to calculate odds ratios, with adjustment for potential confounders. Use of immunosuppressant medication by the index child led to a deficit of risk (odds ratio ¼ 0.37, 95% confidence interval: 0.16, 0.84), while vitamin intake was positively associated with leukemia (odds ratio ¼ 1.66, 95% confidence interval: 1.18, 2.33). Breastfeeding for more than 6 months was also protective (p < 0.05). Results persisted for cases diagnosed with acute lymphoblastic leukemia and for children diagnosed at 1–5 years of age. These findings suggest a role for early immunologic challenge in the expression of childhood leukemia.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/18079130
Citation
Macarthur, A. C., M. L. Mcbride, J. J. Spinelli, S. Tamaro, R. P. Gallagher, and G. P. Theriault. "Risk of Childhood Leukemia Associated with Vaccination, Infection, and Medication Use in Childhood: The Cross-Canada Childhood Leukemia Study." American Journal of Epidemiology 167.5 (2007): 598-606.
“Current hypotheses consonant with the peak in leukemia incidence in early childhood point to an infectious etiology. The authors examined the effect of postnatal exposures predicted to affect early immune functioning, including childhood vaccinations, illness, medication use, and breastfeeding patterns. Children 0–15 years of age diagnosed with leukemia from 1990 to 1994 and resident within principal cities across Canada were eligible for inclusion. Through pediatric oncology centers and population-based cancer registries, 399 cases were ascertained at the time of diagnosis. For each participating case, an age-, gender-, and area-matched control was randomly selected from government health insurance rolls. Risk factor information was obtained through personal interviews with each child’s parents or guardians. Conditional logistic regression was used to calculate odds ratios, with adjustment for potential confounders. Use of immunosuppressant medication by the index child led to a deficit of risk (odds ratio ¼ 0.37, 95% confidence interval: 0.16, 0.84), while vitamin intake was positively associated with leukemia (odds ratio ¼ 1.66, 95% confidence interval: 1.18, 2.33). Breastfeeding for more than 6 months was also protective (p < 0.05). Results persisted for cases diagnosed with acute lymphoblastic leukemia and for children diagnosed at 1–5 years of age. These findings suggest a role for early immunologic challenge in the expression of childhood leukemia.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/18079130
Citation
Macarthur, A. C., M. L. Mcbride, J. J. Spinelli, S. Tamaro, R. P. Gallagher, and G. P. Theriault. "Risk of Childhood Leukemia Associated with Vaccination, Infection, and Medication Use in Childhood: The Cross-Canada Childhood Leukemia Study." American Journal of Epidemiology 167.5 (2007): 598-606.
5. Oncolytic activities of approved mumps and measles vaccines for therapy of ovarian cancer
Abstract
“Oncolytic viruses are promising cytoreductive agents for cancer treatment but extensive human testing will be required before they are made commercially available. Here, we investigated the oncolytic potential of two commercially available live attenuated vaccines, Moraten measles and Jeryl-Lynn mumps, in a murine model of intraperitoneal human ovarian cancer and compared their efficacies against a recombinant oncolytic measles virus (MV-CEA) that is being tested in a phase I clinical trial. The common feature of these viruses is that they express hemagglutinin and fusion therapeutic proteins that can induce extensive fusion of the infected cell with its neighbors, resulting in death of the cell monolayer. In vitro, the three viruses caused intercellular fusion in human ovarian cancer cells but with marked differences in fusion kinetics. MV-CEA was the fastest followed by Jeryl-Lynn mumps virus while Moraten measles virus was the slowest, although all viruses eventually caused comparable cell death 6 days postinfection. Tumor-bearing mice treated with 106 or 107 pfu (one thousand times the vaccine dose) of each of the three viruses responded favorably to therapy with significant prolongations in survival. All three viruses demonstrated equivalent antitumor potency. Commercially available Moraten measles and Jeryl-Lynn mumps vaccines warrant further investigation as potential anticancer agents.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/15746945
Citation
Myers, Rae, Suzanne Greiner, Mary Harvey, Diane Soeffker, Marie Frenzke, Katalin Abraham, Alan Shaw, Shmuel Rozenblatt, Mark J. Federspiel, Stephen J. Russell, and Kah-Whye Peng. "Oncolytic Activities of Approved Mumps and Measles Vaccines for Therapy of Ovarian Cancer." Cancer Gene Therapy 12.7 (2005): 593-99.
“Oncolytic viruses are promising cytoreductive agents for cancer treatment but extensive human testing will be required before they are made commercially available. Here, we investigated the oncolytic potential of two commercially available live attenuated vaccines, Moraten measles and Jeryl-Lynn mumps, in a murine model of intraperitoneal human ovarian cancer and compared their efficacies against a recombinant oncolytic measles virus (MV-CEA) that is being tested in a phase I clinical trial. The common feature of these viruses is that they express hemagglutinin and fusion therapeutic proteins that can induce extensive fusion of the infected cell with its neighbors, resulting in death of the cell monolayer. In vitro, the three viruses caused intercellular fusion in human ovarian cancer cells but with marked differences in fusion kinetics. MV-CEA was the fastest followed by Jeryl-Lynn mumps virus while Moraten measles virus was the slowest, although all viruses eventually caused comparable cell death 6 days postinfection. Tumor-bearing mice treated with 106 or 107 pfu (one thousand times the vaccine dose) of each of the three viruses responded favorably to therapy with significant prolongations in survival. All three viruses demonstrated equivalent antitumor potency. Commercially available Moraten measles and Jeryl-Lynn mumps vaccines warrant further investigation as potential anticancer agents.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/15746945
Citation
Myers, Rae, Suzanne Greiner, Mary Harvey, Diane Soeffker, Marie Frenzke, Katalin Abraham, Alan Shaw, Shmuel Rozenblatt, Mark J. Federspiel, Stephen J. Russell, and Kah-Whye Peng. "Oncolytic Activities of Approved Mumps and Measles Vaccines for Therapy of Ovarian Cancer." Cancer Gene Therapy 12.7 (2005): 593-99.
6. Mumps and ovarian cancer: modern interpretation of an historic association
Abstract
“Background
Epidemiologic studies found childhood mumps might protect against ovarian cancer. To explain this association, we investigated whether mumps might engender immunity to ovarian cancer through antibodies against the cancer-associated antigen MUC1 abnormally expressed in the inflamed parotid gland.
Methods
Through various health agencies, we obtained sera from 161 cases with mumps parotitis. Sera were obtained from 194 healthy controls. We used an ELISA to measure anti-MUC1 antibodies and electro-chemiluminescence assays to measure MUC1 and CA 125. Log-transformed measurements were analyzed by t-tests, generalized linear models, and Pearson or Spearman correlations. We also conducted a meta-analysis of all published studies regarding mumps and ovarian cancer
Results
Adjusting for assay batch, age, and sex, the level of anti-MUC1 antibodies was significantly higher in mumps cases compared to controls (p = 0.002). Free circulating levels of CA 125, but not MUC1, were also higher in cases (p = 0.02). From the meta-analysis, the pooled odds ratio estimate (and 95% CI) for the mumps and ovarian cancer association was 0.81 (0.68–0.96) (p = 0.01).
Conclusion
Mumps parotitis may lead to expression and immune recognition of a tumorassociated form of MUC1 and create effective immune surveillance of ovarian cancer cells that express this form of MUC1”
Link
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951028/
Citation
Cramer, Daniel W., Allison F. Vitonis, Simone P. Pinheiro, John R. Mckolanis, Raina N. Fichorova, Kevin E. Brown, Todd F. Hatchette, and Olivera J. Finn. "Mumps and Ovarian Cancer: Modern Interpretation of an Historic Association." Cancer Causes & Control 21.8 (2010): 1193-201.
“Background
Epidemiologic studies found childhood mumps might protect against ovarian cancer. To explain this association, we investigated whether mumps might engender immunity to ovarian cancer through antibodies against the cancer-associated antigen MUC1 abnormally expressed in the inflamed parotid gland.
Methods
Through various health agencies, we obtained sera from 161 cases with mumps parotitis. Sera were obtained from 194 healthy controls. We used an ELISA to measure anti-MUC1 antibodies and electro-chemiluminescence assays to measure MUC1 and CA 125. Log-transformed measurements were analyzed by t-tests, generalized linear models, and Pearson or Spearman correlations. We also conducted a meta-analysis of all published studies regarding mumps and ovarian cancer
Results
Adjusting for assay batch, age, and sex, the level of anti-MUC1 antibodies was significantly higher in mumps cases compared to controls (p = 0.002). Free circulating levels of CA 125, but not MUC1, were also higher in cases (p = 0.02). From the meta-analysis, the pooled odds ratio estimate (and 95% CI) for the mumps and ovarian cancer association was 0.81 (0.68–0.96) (p = 0.01).
Conclusion
Mumps parotitis may lead to expression and immune recognition of a tumorassociated form of MUC1 and create effective immune surveillance of ovarian cancer cells that express this form of MUC1”
Link
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951028/
Citation
Cramer, Daniel W., Allison F. Vitonis, Simone P. Pinheiro, John R. Mckolanis, Raina N. Fichorova, Kevin E. Brown, Todd F. Hatchette, and Olivera J. Finn. "Mumps and Ovarian Cancer: Modern Interpretation of an Historic Association." Cancer Causes & Control 21.8 (2010): 1193-201.
7. Acute infections as a means of cancer prevention: Opposing effects to chronic infections?
Abstract
“Purpose: Epidemiological studies have found an inverse association between acute infections and cancer development. In this paper, we review the evidence examining this potentially antagonistic relationship. Methods: In addition to a review of the historical literature, we examined the recent epidemiological evidence on the relationship between acute infections and subsequent cancer development in adult life. We also discuss the impact of chronic infections on tumor development and the influence of the immune system in this process. Results: Exposures to febrile infectious childhood diseases were associated with subsequently reduced risks for melanoma, ovary, and multiple cancers combined, significant in the latter two groups. Epidemiological studies on common acute infections in adults and subsequent cancer development found these infections to be associated with reduced risks for meningioma, glioma, melanoma and multiple cancers combined, significantly for the latter three groups. Overall, risk reduction increased with the frequency of infections, with febrile infections affording the greatest protection. In contrast to acute infections, chronic infections can be viewed as resulting from a failed immune response and an increasing number have been associated with an elevated cancer risk. Conclusion: Infections may play a paradoxical role in cancer development with chronic infections often being tumorigenic and acute infections being antagonistic to cancer. # 2006 International Society for Preventive Oncology.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/16490323
Citation
Cann, Stephen A. Hoption, J.p. Van Netten, and C. Van Netten. "Acute Infections as a Means of Cancer Prevention: Opposing Effects to Chronic Infections?" Cancer Detection and Prevention 30.1 (2006): 83-93.
“Purpose: Epidemiological studies have found an inverse association between acute infections and cancer development. In this paper, we review the evidence examining this potentially antagonistic relationship. Methods: In addition to a review of the historical literature, we examined the recent epidemiological evidence on the relationship between acute infections and subsequent cancer development in adult life. We also discuss the impact of chronic infections on tumor development and the influence of the immune system in this process. Results: Exposures to febrile infectious childhood diseases were associated with subsequently reduced risks for melanoma, ovary, and multiple cancers combined, significant in the latter two groups. Epidemiological studies on common acute infections in adults and subsequent cancer development found these infections to be associated with reduced risks for meningioma, glioma, melanoma and multiple cancers combined, significantly for the latter three groups. Overall, risk reduction increased with the frequency of infections, with febrile infections affording the greatest protection. In contrast to acute infections, chronic infections can be viewed as resulting from a failed immune response and an increasing number have been associated with an elevated cancer risk. Conclusion: Infections may play a paradoxical role in cancer development with chronic infections often being tumorigenic and acute infections being antagonistic to cancer. # 2006 International Society for Preventive Oncology.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/16490323
Citation
Cann, Stephen A. Hoption, J.p. Van Netten, and C. Van Netten. "Acute Infections as a Means of Cancer Prevention: Opposing Effects to Chronic Infections?" Cancer Detection and Prevention 30.1 (2006): 83-93.
8. A meta-analysis of the association between day-care attendance and childhood acute lymphoblastic leukaemia
Abstract
“Background
Childhood acute lymphoblastic leukaemia (ALL) may be the result of a rare response to common infection(s) acquired by personal contact with infected individuals. A meta-analysis was conducted to examine the relationship between day-care attendance and risk of childhood ALL, specifically to address whether early-life exposure to infection is protective against ALL.
Methods
Searches of the PubMed database and bibliographies of publications on childhood leukaemia and infections were conducted. Observational studies of any size or location and published in English resulted in the inclusion of 14 case–control studies.
Results
The combined odds ratio (OR) based on the random effects model indicated that day-care attendance is associated with a reduced risk of ALL [OR ¼ 0.76, 95% confidence interval (CI): 0.67, 0.87]. In subgroup analyses evaluating the influence of timing of exposure, a similarly reduced effect was observed for both day-care attendance occurring early in life (42 years of age) (OR ¼ 0.79, 95% CI: 0.65, 0.95) and day-care attendance with unspecified timing (anytime prior to diagnosis) (OR ¼ 0.81, 95% CI: 0.70, 0.94). Similar findings were observed with seven studies in which common ALL were analysed separately. The reduced risk estimates persisted in sensitivity analyses that examined the sources of study heterogeneity.
Conclusions
This analysis provides strong support for an association between exposure to common infections in early childhood and a reduced risk of ALL. Implications of a ‘hygiene’-related aetiology suggest that some form of prophylactic intervention in infancy may be possible.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/20110276
Citation
Urayama, K. Y., P. A. Buffler, E. R. Gallagher, J. M. Ayoob, and X. Ma. "A Meta-analysis of the Association between Day-care Attendance and Childhood Acute Lymphoblastic Leukaemia." International Journal of Epidemiology 39.3 (2010): 718-32
“Background
Childhood acute lymphoblastic leukaemia (ALL) may be the result of a rare response to common infection(s) acquired by personal contact with infected individuals. A meta-analysis was conducted to examine the relationship between day-care attendance and risk of childhood ALL, specifically to address whether early-life exposure to infection is protective against ALL.
Methods
Searches of the PubMed database and bibliographies of publications on childhood leukaemia and infections were conducted. Observational studies of any size or location and published in English resulted in the inclusion of 14 case–control studies.
Results
The combined odds ratio (OR) based on the random effects model indicated that day-care attendance is associated with a reduced risk of ALL [OR ¼ 0.76, 95% confidence interval (CI): 0.67, 0.87]. In subgroup analyses evaluating the influence of timing of exposure, a similarly reduced effect was observed for both day-care attendance occurring early in life (42 years of age) (OR ¼ 0.79, 95% CI: 0.65, 0.95) and day-care attendance with unspecified timing (anytime prior to diagnosis) (OR ¼ 0.81, 95% CI: 0.70, 0.94). Similar findings were observed with seven studies in which common ALL were analysed separately. The reduced risk estimates persisted in sensitivity analyses that examined the sources of study heterogeneity.
Conclusions
This analysis provides strong support for an association between exposure to common infections in early childhood and a reduced risk of ALL. Implications of a ‘hygiene’-related aetiology suggest that some form of prophylactic intervention in infancy may be possible.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/20110276
Citation
Urayama, K. Y., P. A. Buffler, E. R. Gallagher, J. M. Ayoob, and X. Ma. "A Meta-analysis of the Association between Day-care Attendance and Childhood Acute Lymphoblastic Leukaemia." International Journal of Epidemiology 39.3 (2010): 718-32
9. Age of exposure to infections and risk of childhood leukaemia
Abstract
“Building on previous suggestions,'-3 we speculated that childhood leukaemia might be a rare manifestation of an infection that would have remained subclinical at an earlier age. Several ecological studies have produced evidence to support a hypothesis based on herd immunity, but others have not.4 We reasoned that a better approach would be to compare cases of childhood leukaemia with controls with respect to attendance at creches, where crowding of children ensures effective transmission of infectious agents.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/8219951
Citation
Petridou, E., D. Kassimos, M. Kalmanti, H. Kosmidis, S. Haidas, V. Flytzani, D. Tong, and D. Trichopoulos. "Age of Exposure to Infections and Risk of Childhood Leukaemia." Bmj 307.6907 (1993): 774.
“Building on previous suggestions,'-3 we speculated that childhood leukaemia might be a rare manifestation of an infection that would have remained subclinical at an earlier age. Several ecological studies have produced evidence to support a hypothesis based on herd immunity, but others have not.4 We reasoned that a better approach would be to compare cases of childhood leukaemia with controls with respect to attendance at creches, where crowding of children ensures effective transmission of infectious agents.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/8219951
Citation
Petridou, E., D. Kassimos, M. Kalmanti, H. Kosmidis, S. Haidas, V. Flytzani, D. Tong, and D. Trichopoulos. "Age of Exposure to Infections and Risk of Childhood Leukaemia." Bmj 307.6907 (1993): 774.
10. Cancer increased after a reduction of infections in the first half of this century in Italy: Etiologic and preventive implications
Abstract
“Two rate ratios indicating the disappearance of infections and the growth of tumours, respectively, were simultaneously plotted against the calendar years of occurrence in a period during which mortality rates were reasonably comparable to incidences. The transformation used gave upward trend time variations for infectious diseases, providing strong evidence that in Italy during the ®rst half of this century variations in infectious diseases preceded variations in cancer. While some bacteria and viruses are known to be cancer agents, sparse studies indicate that a host's immune response to infection may destroy cancer cells. With a decreasing mortality from infectious illnesses, there may have been a reduction in the activation of immunological mechanisms against transformed cells in early phases of carcinogenesis. If cancer growth is a consequence of a lower exposure to chronic sublethal doses of microbial agents, bacterial derivates could be potentially useful in cancer chemoprevention.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/9928868
Citation
Hemminki, K. "Familial Risks for Cervical Tumors in Full and Half Siblings: Etiologic Apportioning." Cancer Epidemiology Biomarkers & Prevention 15.7 (2006): 1413-414.
“Two rate ratios indicating the disappearance of infections and the growth of tumours, respectively, were simultaneously plotted against the calendar years of occurrence in a period during which mortality rates were reasonably comparable to incidences. The transformation used gave upward trend time variations for infectious diseases, providing strong evidence that in Italy during the ®rst half of this century variations in infectious diseases preceded variations in cancer. While some bacteria and viruses are known to be cancer agents, sparse studies indicate that a host's immune response to infection may destroy cancer cells. With a decreasing mortality from infectious illnesses, there may have been a reduction in the activation of immunological mechanisms against transformed cells in early phases of carcinogenesis. If cancer growth is a consequence of a lower exposure to chronic sublethal doses of microbial agents, bacterial derivates could be potentially useful in cancer chemoprevention.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/9928868
Citation
Hemminki, K. "Familial Risks for Cervical Tumors in Full and Half Siblings: Etiologic Apportioning." Cancer Epidemiology Biomarkers & Prevention 15.7 (2006): 1413-414.
11. Childhood Hodgkin’s lymphoma, non-Hodgkin’s lymphoma and factors related to the immune system: The Escale Study (SFCE)
Abstract
“The study investigated the role of factors considered related to the early stimulation of the immune system in the aetiology of childhood lymphoma. The national registry-based case–control study, Escale, was carried out in France over the period 2003–2004. Population controls were frequency matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. Data from 128 cases of Hodgkin’s lymphoma (HL) aged 5–14 years, 164 cases of non-Hodgkin’s lymphoma (NHL) aged 2–14 years and 1,312 controls were analyzed. Negative associations were observed between HL and day care attendance [OR 5 0.5 (0.2–1.2)] and between HL and repeated early common infections among non-breastfed children [OR 5 0.3 (.2–0.7), p 5 0.003] [OR for breastfed children: 1.0 (.5– 2.1)], but not for the other factors investigated. Negative associations were observed between NHL and birth order 3 or more [OR 5 0.7 (0.4–1.1)], prolonged breastfeeding [OR 5 0.5 (0.3–1.0)], regular contact with farm animals [OR 5 0.5 (0.3–1.0)], frequent farm visits in early life [OR 5 0.6 (0.4–1.1)] and history of asthma [OR 5 0.6 (0.3–1.1)]. In conclusion, the results partly support the hypothesis that an abnormal maturation of the immune system may play a role in childhood HL or NHL, and call for further investigations.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/21170962
Citation
Rudant, Je´re´mie, Laurent Orsi, Alain Monnereau, Catherine Patte, Hélène Pacquement, Judith Landman-Parker, Christophe Bergeron, Alain Robert, Gérard Michel, Anne Lambilliotte, Nathalie Aladjidi, Virginie Gandemer, Patrick Lutz, Geneviève Margueritte, Dominique Plantaz, Françoise Méchinaud, Denis Hémon, and Jacqueline Clavel. "Childhood Hodgkin's Lymphoma, Non-hodgkin's Lymphoma and Factors Related to the Immune System: The Escale Study (SFCE)." International Journal of Cancer 129.9 (2011): 2236-247.
“The study investigated the role of factors considered related to the early stimulation of the immune system in the aetiology of childhood lymphoma. The national registry-based case–control study, Escale, was carried out in France over the period 2003–2004. Population controls were frequency matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. Data from 128 cases of Hodgkin’s lymphoma (HL) aged 5–14 years, 164 cases of non-Hodgkin’s lymphoma (NHL) aged 2–14 years and 1,312 controls were analyzed. Negative associations were observed between HL and day care attendance [OR 5 0.5 (0.2–1.2)] and between HL and repeated early common infections among non-breastfed children [OR 5 0.3 (.2–0.7), p 5 0.003] [OR for breastfed children: 1.0 (.5– 2.1)], but not for the other factors investigated. Negative associations were observed between NHL and birth order 3 or more [OR 5 0.7 (0.4–1.1)], prolonged breastfeeding [OR 5 0.5 (0.3–1.0)], regular contact with farm animals [OR 5 0.5 (0.3–1.0)], frequent farm visits in early life [OR 5 0.6 (0.4–1.1)] and history of asthma [OR 5 0.6 (0.3–1.1)]. In conclusion, the results partly support the hypothesis that an abnormal maturation of the immune system may play a role in childhood HL or NHL, and call for further investigations.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/21170962
Citation
Rudant, Je´re´mie, Laurent Orsi, Alain Monnereau, Catherine Patte, Hélène Pacquement, Judith Landman-Parker, Christophe Bergeron, Alain Robert, Gérard Michel, Anne Lambilliotte, Nathalie Aladjidi, Virginie Gandemer, Patrick Lutz, Geneviève Margueritte, Dominique Plantaz, Françoise Méchinaud, Denis Hémon, and Jacqueline Clavel. "Childhood Hodgkin's Lymphoma, Non-hodgkin's Lymphoma and Factors Related to the Immune System: The Escale Study (SFCE)." International Journal of Cancer 129.9 (2011): 2236-247.
12. Cytotoxicity of glioblastoma cells mediated ex vivo by varicellazoster virus-specific T cells
Abstract
“Clinical or laboratory evidence of varicella-zoster virus (VZV) infection has been consistently associated with lower glioma risk in case-control studies, suggesting a protective effect of VZV against glioma. We formulated the following explanatory hypotheses: reactivated VZV preferentially infects and kills gliomas compared to normal parenchyma; and VZV-specific cytotoxic T lymphocytes (CTL) cross-react with gliomas. We established an ex vivo model of VZV infection, which showed that glioma cell lines and primary astrocytes were equally permissive to VZV infection and had similar 15% average decrease in viability upon infection. In co-cultures, the relative growth of glioma cells and astrocytes was not affected by the VZV infection. However, VZV stimulated, but not mock stimulated, peripheral blood mononuclear cells from VZV-seropositive individuals recognized and killed HLA class I-matched glioma cells (mean±SE decrease in viability of 26 ± 12%, p = 0.04), but not matched astrocytes. VZV infection of the glioma cells did not affect the T cell-mediated killing. Taken together, these data suggest that ex vivo VZV infection has similar direct effects on glioma cells and astrocytes. The protective effect of prior VZV infection against the incidence of glioma may be mediated by CTL that recognizes epitopes shared by VZV and glioma cells”
Link
https://www.ncbi.nlm.nih.gov/pubmed/21792750
Citation
Canniff, Jennifer, Andrew M. Donson, Nicholas K. Foreman, and Adriana Weinberg. "Cytotoxicity of Glioblastoma Cells Mediated Ex Vivo by Varicella-zoster Virus-specific T Cells." Journal of NeuroVirology 17.5 (2011): 448-54.
“Clinical or laboratory evidence of varicella-zoster virus (VZV) infection has been consistently associated with lower glioma risk in case-control studies, suggesting a protective effect of VZV against glioma. We formulated the following explanatory hypotheses: reactivated VZV preferentially infects and kills gliomas compared to normal parenchyma; and VZV-specific cytotoxic T lymphocytes (CTL) cross-react with gliomas. We established an ex vivo model of VZV infection, which showed that glioma cell lines and primary astrocytes were equally permissive to VZV infection and had similar 15% average decrease in viability upon infection. In co-cultures, the relative growth of glioma cells and astrocytes was not affected by the VZV infection. However, VZV stimulated, but not mock stimulated, peripheral blood mononuclear cells from VZV-seropositive individuals recognized and killed HLA class I-matched glioma cells (mean±SE decrease in viability of 26 ± 12%, p = 0.04), but not matched astrocytes. VZV infection of the glioma cells did not affect the T cell-mediated killing. Taken together, these data suggest that ex vivo VZV infection has similar direct effects on glioma cells and astrocytes. The protective effect of prior VZV infection against the incidence of glioma may be mediated by CTL that recognizes epitopes shared by VZV and glioma cells”
Link
https://www.ncbi.nlm.nih.gov/pubmed/21792750
Citation
Canniff, Jennifer, Andrew M. Donson, Nicholas K. Foreman, and Adriana Weinberg. "Cytotoxicity of Glioblastoma Cells Mediated Ex Vivo by Varicella-zoster Virus-specific T Cells." Journal of NeuroVirology 17.5 (2011): 448-54.
13. Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings from UK case-control study
Abstract
Objective
To test the hypothesis that reduced exposure to common infections in the first year of life increases the risk of developing acute lymphoblastic leukaemia.
Design and setting
The United Kingdom childhood cancer study (UKCCS) is a large population based case-control study of childhood cancer across 10 regions of the UK.
Participants
6305 children (aged 2-14 years) without cancer; 3140 children with cancer (diagnosed 1991-6), of whom 1286 had acute lymphoblastic leukaemia (ALL). Main outcome measure Day care and social activity during the first year of life were used as proxies for potential exposure to infection in infancy.
Results
Increasing levels of social activity were associated with consistent reductions in risk of ALL; a dose-response trend was seen. When children whose mothers reported no regular activity outside the family were used as the reference group, odds ratios for increasing levels of activity were 0.73 (95% confidence interval 0.62 to 0.87) for any social activity, 0.62 (0.51 to 0.75) for regular day care outside the home, and 0.48 (0.37 to 0.62) for formal day care (attendance at facility with at least four children at least twice a week) (P value for trend < 0.001). Although not as striking, results for non-ALL malignancies showed a similar pattern (P value for trend < 0.001). When children with non-ALL malignancies were taken as the reference group, a significant protective effect for ALL was seen only for formal day care (odds ratio = 0.69, 0.51 to 0.93; P = 0.02). Similar results were obtained for B cell precursor common ALL and other subgroups, as well as for cases diagnosed above and below age 5 years.
Conclusion
These results support the hypothesis that reduced exposure to infection in the first few months of life increases the risk of developing acute lymphoblastic leukaemia.”
Link
http://www.bmj.com/content/330/7503/1294
Citation
Gilham, C. "Day Care in Infancy and Risk of Childhood Acute Lymphoblastic Leukaemia: Findings from UK Case-control Study." Bmj 330.7503 (2005): 1294-0.
Objective
To test the hypothesis that reduced exposure to common infections in the first year of life increases the risk of developing acute lymphoblastic leukaemia.
Design and setting
The United Kingdom childhood cancer study (UKCCS) is a large population based case-control study of childhood cancer across 10 regions of the UK.
Participants
6305 children (aged 2-14 years) without cancer; 3140 children with cancer (diagnosed 1991-6), of whom 1286 had acute lymphoblastic leukaemia (ALL). Main outcome measure Day care and social activity during the first year of life were used as proxies for potential exposure to infection in infancy.
Results
Increasing levels of social activity were associated with consistent reductions in risk of ALL; a dose-response trend was seen. When children whose mothers reported no regular activity outside the family were used as the reference group, odds ratios for increasing levels of activity were 0.73 (95% confidence interval 0.62 to 0.87) for any social activity, 0.62 (0.51 to 0.75) for regular day care outside the home, and 0.48 (0.37 to 0.62) for formal day care (attendance at facility with at least four children at least twice a week) (P value for trend < 0.001). Although not as striking, results for non-ALL malignancies showed a similar pattern (P value for trend < 0.001). When children with non-ALL malignancies were taken as the reference group, a significant protective effect for ALL was seen only for formal day care (odds ratio = 0.69, 0.51 to 0.93; P = 0.02). Similar results were obtained for B cell precursor common ALL and other subgroups, as well as for cases diagnosed above and below age 5 years.
Conclusion
These results support the hypothesis that reduced exposure to infection in the first few months of life increases the risk of developing acute lymphoblastic leukaemia.”
Link
http://www.bmj.com/content/330/7503/1294
Citation
Gilham, C. "Day Care in Infancy and Risk of Childhood Acute Lymphoblastic Leukaemia: Findings from UK Case-control Study." Bmj 330.7503 (2005): 1294-0.
14. Does Prior Infection with Varicella-Zoster Virus Influence Risk of Adult Glioma?
Abstract
“To evaluate a possible association between varicella-zoster virus infection and glioma, the authors asked adults with glioma (n = 462) whose tumors were diagnosed between August 1,1991, and March 31,1994, and age-, sex-, and ethnicity-matched controls (n - 443) about their histories of chickenpox or shingles. Cases were significantly less likely than controls to report a history of erther chickenpox (odds ratio = 0.4, 95% confidence interval (Cl) 0.3-0.6) or shingles (odds ratio = 0.5, 95% Cl 0.3-0.8). To obtain serologic support for these findings, the authors conducted double-blind enzyme-linked immunosorbent assays for immunoglobuhn G antibodies to varicella-zoster virus among 167 serf-reporting subjects for whom blood samples were available. Cases and controls reporting no history of chickenpox were equally likely to test positive (73% vs. 75%), but among those reporting a positive history, cases were less likely than were controls to test positive (71 % vs. 85%). Despite the misclassification, an odds ratio of 0.6 was obtained using either serologic data (95% Cl 0.3-1.3) or reported history of chickenpox (95% Cl 0.3-1.1) in this subgroup of subjects. This suggests that adults with glioma were less likely than controls erther to have had pnor varicella-zoster virus infection or to have an immunoglobulin G antibody response adequate to indicate positivity. Since either explanation suggests novel mechanisms for brain tumor pathogenesis, these findings require coiToboration and elaboration.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/9098175
Citation
Wrensch, M., A. Weinberg, J. Wiencke, H. Masters, R. Miike, G. Barger, and M. Lee. "Does Prior Infection with Varicella-Zoster Virus Influence Risk of Adult Glioma?" American Journal of Epidemiology 145.7 (1997): 594-97.
“To evaluate a possible association between varicella-zoster virus infection and glioma, the authors asked adults with glioma (n = 462) whose tumors were diagnosed between August 1,1991, and March 31,1994, and age-, sex-, and ethnicity-matched controls (n - 443) about their histories of chickenpox or shingles. Cases were significantly less likely than controls to report a history of erther chickenpox (odds ratio = 0.4, 95% confidence interval (Cl) 0.3-0.6) or shingles (odds ratio = 0.5, 95% Cl 0.3-0.8). To obtain serologic support for these findings, the authors conducted double-blind enzyme-linked immunosorbent assays for immunoglobuhn G antibodies to varicella-zoster virus among 167 serf-reporting subjects for whom blood samples were available. Cases and controls reporting no history of chickenpox were equally likely to test positive (73% vs. 75%), but among those reporting a positive history, cases were less likely than were controls to test positive (71 % vs. 85%). Despite the misclassification, an odds ratio of 0.6 was obtained using either serologic data (95% Cl 0.3-1.3) or reported history of chickenpox (95% Cl 0.3-1.1) in this subgroup of subjects. This suggests that adults with glioma were less likely than controls erther to have had pnor varicella-zoster virus infection or to have an immunoglobulin G antibody response adequate to indicate positivity. Since either explanation suggests novel mechanisms for brain tumor pathogenesis, these findings require coiToboration and elaboration.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/9098175
Citation
Wrensch, M., A. Weinberg, J. Wiencke, H. Masters, R. Miike, G. Barger, and M. Lee. "Does Prior Infection with Varicella-Zoster Virus Influence Risk of Adult Glioma?" American Journal of Epidemiology 145.7 (1997): 594-97.
15. Early life exposure to infections and risk of childhood acute lymphoblastic leukemia
Abstract
“Evidence from a growing number of studies indicates that exposure to common infections early in life may be protective against childhood acute lymphoblastic leukemia (ALL). We examined the relationship between three measures of early life exposure to infections—daycare attendance, birth order and common childhood infections in infancy—with the risk of ALL in non-Hispanic white and Hispanic children, two ethnicities that show sociodemographic differences. The analysis included 669 ALL cases (284 non-Hispanic whites and 385 Hispanics) and 977 controls (458 nonHispanic whites and 519 Hispanics) ages 1–14 years enrolled in the Northern California Childhood Leukemia Study (NCCLS). When the three measures were evaluated separately, daycare attendance by the age of 6 months (odds ratio [OR] for each thousand child-hours of exposure = 0.90, 95% confidence interval [CI]: 0.82–1.00) and birth order (OR for having an older sibling = 0.68, 95% CI: 0.50–0.92) were associated with a reduced risk of ALL among nonHispanic white children but not Hispanic children, whereas ear infection before age 6 months was protective in both ethnic groups. When the three measures were assessed simultaneously, the influence of daycare attendance (OR = 0.83, 95% CI: 0.73–0.94) and having an older sibling (OR = 0.59, 95% CI: 0.43–0.83) became stronger for non-Hispanic white children. In Hispanic children, a strong reduction in risk associated with ear infections persisted (OR = 0.45, 95% CI: 0.25–0.79). Evidence of a protective role for infection-related exposures early in life is supported by findings in both the non-Hispanic white and Hispanic populations within the NCCLS.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/21280034
Citation
Urayama, Kevin Y., Xiaomei Ma, Steve Selvin, Catherine Metayer, Anand P. Chokkalingam, Joseph L. Wiemels, Monique Does, Jeffrey Chang, Alan Wong, Elizabeth Trachtenberg, and Patricia A. Buffler. "Early Life Exposure to Infections and Risk of Childhood Acute Lymphoblastic Leukemia." International Journal of Cancer 128.7 (2010): 1632-643.
“Evidence from a growing number of studies indicates that exposure to common infections early in life may be protective against childhood acute lymphoblastic leukemia (ALL). We examined the relationship between three measures of early life exposure to infections—daycare attendance, birth order and common childhood infections in infancy—with the risk of ALL in non-Hispanic white and Hispanic children, two ethnicities that show sociodemographic differences. The analysis included 669 ALL cases (284 non-Hispanic whites and 385 Hispanics) and 977 controls (458 nonHispanic whites and 519 Hispanics) ages 1–14 years enrolled in the Northern California Childhood Leukemia Study (NCCLS). When the three measures were evaluated separately, daycare attendance by the age of 6 months (odds ratio [OR] for each thousand child-hours of exposure = 0.90, 95% confidence interval [CI]: 0.82–1.00) and birth order (OR for having an older sibling = 0.68, 95% CI: 0.50–0.92) were associated with a reduced risk of ALL among nonHispanic white children but not Hispanic children, whereas ear infection before age 6 months was protective in both ethnic groups. When the three measures were assessed simultaneously, the influence of daycare attendance (OR = 0.83, 95% CI: 0.73–0.94) and having an older sibling (OR = 0.59, 95% CI: 0.43–0.83) became stronger for non-Hispanic white children. In Hispanic children, a strong reduction in risk associated with ear infections persisted (OR = 0.45, 95% CI: 0.25–0.79). Evidence of a protective role for infection-related exposures early in life is supported by findings in both the non-Hispanic white and Hispanic populations within the NCCLS.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/21280034
Citation
Urayama, Kevin Y., Xiaomei Ma, Steve Selvin, Catherine Metayer, Anand P. Chokkalingam, Joseph L. Wiemels, Monique Does, Jeffrey Chang, Alan Wong, Elizabeth Trachtenberg, and Patricia A. Buffler. "Early Life Exposure to Infections and Risk of Childhood Acute Lymphoblastic Leukemia." International Journal of Cancer 128.7 (2010): 1632-643.
16.
17. Exposure to childhood infections and risk of Epstein-Barr virus–defined Hodgkin’s lymphoma in women
Abstract
“The role of Epstein-Barr virus (EBV) in Hodgkin’s lymphoma (HL) etiology remains unresolved as EBV is detected in only some HL tumors and few studies have tried to reconcile its presence with factors suggesting viral etiology (e.g., childhood social class, infection history). In a population-based case-control study of San Francisco Bay area women, we analyzed interview data by tumor EBV status. Among 211 young adult cases, EBV-positive HL (11%) was associated with a single vs. shared bedroom at age 11 (OR ¼ 4.0, 95% CI 1.1–14.4); risk was decreased for common childhood infections (OR ¼ 0.3, 95% CI 0.1–1.0), including measles before age 10, but not with prior infectious mononucleosis (IM), which is delayed EBV infection. No study factors affected risk of young adult EBV-negative HL. Among 57 older adult cases, EBV-positive HL (23%) was unrelated to study factors; EBV-negative HL was associated with a single bedroom at age 11 (OR ¼ 3.6, 95% CI 1.5–9.1) and IM in family members (OR ¼ 3.1, 95% CI 1.1–9.0). Thus, delayed exposure to infection may increase risk of EBV-positive HL in young adults, but risk patterns differ in younger and older women for both EBV-positive and -negative HL. Late EBV infection does not appear relevant to risk, suggesting that other pathogens impact HL etiology in affluent female populations. Inconsistency of findings with prior studies may reflect failure of study risk factors to proxy meaningful exposures, risk differences by gender, or selection or misclassification bias. Null findings for EBV-negative HL indicate that etiologic models should be reconsidered for this common form.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/15700307
Citation
Glaser, Sally L., Theresa H. M. Keegan, Christina A. Clarke, Muoi Trinh, Ronald F. Dorfman, Risa B. Mann, Joseph A. Digiuseppe, and Richard F. Ambinder. "Exposure to Childhood Infections and Risk of Epstein-Barr Virus-defined Hodgkin's Lymphoma in Women." International Journal of Cancer 115.4 (2005): 599-605.
“The role of Epstein-Barr virus (EBV) in Hodgkin’s lymphoma (HL) etiology remains unresolved as EBV is detected in only some HL tumors and few studies have tried to reconcile its presence with factors suggesting viral etiology (e.g., childhood social class, infection history). In a population-based case-control study of San Francisco Bay area women, we analyzed interview data by tumor EBV status. Among 211 young adult cases, EBV-positive HL (11%) was associated with a single vs. shared bedroom at age 11 (OR ¼ 4.0, 95% CI 1.1–14.4); risk was decreased for common childhood infections (OR ¼ 0.3, 95% CI 0.1–1.0), including measles before age 10, but not with prior infectious mononucleosis (IM), which is delayed EBV infection. No study factors affected risk of young adult EBV-negative HL. Among 57 older adult cases, EBV-positive HL (23%) was unrelated to study factors; EBV-negative HL was associated with a single bedroom at age 11 (OR ¼ 3.6, 95% CI 1.5–9.1) and IM in family members (OR ¼ 3.1, 95% CI 1.1–9.0). Thus, delayed exposure to infection may increase risk of EBV-positive HL in young adults, but risk patterns differ in younger and older women for both EBV-positive and -negative HL. Late EBV infection does not appear relevant to risk, suggesting that other pathogens impact HL etiology in affluent female populations. Inconsistency of findings with prior studies may reflect failure of study risk factors to proxy meaningful exposures, risk differences by gender, or selection or misclassification bias. Null findings for EBV-negative HL indicate that etiologic models should be reconsidered for this common form.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/15700307
Citation
Glaser, Sally L., Theresa H. M. Keegan, Christina A. Clarke, Muoi Trinh, Ronald F. Dorfman, Risa B. Mann, Joseph A. Digiuseppe, and Richard F. Ambinder. "Exposure to Childhood Infections and Risk of Epstein-Barr Virus-defined Hodgkin's Lymphoma in Women." International Journal of Cancer 115.4 (2005): 599-605.
18. History of Chickenpox and Shingles and Prevalence of Antibodies to Varicella-Zoster Virus and Three Other Herpesviruses among Adults with Glioma and Controls
Abstract
“Whether viruses or immunologic factors might cause or prevent human brain cancer is of interest. Statistically significant inverse associations of adult glioma with history of chickenpox and immunoglobulin G antibodies to varicella-zoster virus have been reported. The authors evaluate associations of immunoglobulin G antibodies to varicella-zoster virus and three other herpesviruses among 229 adults with glioma and 289 controls in the San Francisco Bay Area Adult Glioma Study (1997–2000). Cases were less likely than controls to report a history of chickenpox (for self-reported cases vs. controls: the age-, gender-, and ethnicity-adjusted odds ratio ¼ 0.59, 95% confidence interval: 0.40, 0.86), and they also had lower levels of immunoglobulin G to varicella-zoster virus (for being in the highest quartile vs. the lowest quartile: the age-, gender-, and ethnicity-adjusted odds ratio ¼ 0.41, 95% confidence interval: 0.24, 0.70). The inverse association with anti-varicella-zoster virus immunoglobulin G was most marked for glioblastoma multiforme cases versus controls and was only somewhat attenuated by excluding subjects taking high-dose steroids and other medications. Cases and controls did not differ notably for positivity to three other herpesviruses, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus. Cohort studies may help to clarify the nature of the association between immunity to and/or clinical manifestations of varicella-zoster virus and glioblastoma.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/15870157
Citation
Wrensch, M., A. Weinberg, J. Wiencke, R. Miike, J. Sison, J. Wiemels, G. Barger, G. Delorenze, K. Aldape, and K. Kelsey. "History of Chickenpox and Shingles and Prevalence of Antibodies to Varicella-Zoster Virus and Three Other Herpesviruses among Adults with Glioma and Controls." American Journal of Epidemiology 161.10 (2005): 929-38
“Whether viruses or immunologic factors might cause or prevent human brain cancer is of interest. Statistically significant inverse associations of adult glioma with history of chickenpox and immunoglobulin G antibodies to varicella-zoster virus have been reported. The authors evaluate associations of immunoglobulin G antibodies to varicella-zoster virus and three other herpesviruses among 229 adults with glioma and 289 controls in the San Francisco Bay Area Adult Glioma Study (1997–2000). Cases were less likely than controls to report a history of chickenpox (for self-reported cases vs. controls: the age-, gender-, and ethnicity-adjusted odds ratio ¼ 0.59, 95% confidence interval: 0.40, 0.86), and they also had lower levels of immunoglobulin G to varicella-zoster virus (for being in the highest quartile vs. the lowest quartile: the age-, gender-, and ethnicity-adjusted odds ratio ¼ 0.41, 95% confidence interval: 0.24, 0.70). The inverse association with anti-varicella-zoster virus immunoglobulin G was most marked for glioblastoma multiforme cases versus controls and was only somewhat attenuated by excluding subjects taking high-dose steroids and other medications. Cases and controls did not differ notably for positivity to three other herpesviruses, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus. Cohort studies may help to clarify the nature of the association between immunity to and/or clinical manifestations of varicella-zoster virus and glioblastoma.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/15870157
Citation
Wrensch, M., A. Weinberg, J. Wiencke, R. Miike, J. Sison, J. Wiemels, G. Barger, G. Delorenze, K. Aldape, and K. Kelsey. "History of Chickenpox and Shingles and Prevalence of Antibodies to Varicella-Zoster Virus and Three Other Herpesviruses among Adults with Glioma and Controls." American Journal of Epidemiology 161.10 (2005): 929-38
19. Increased Risk of Second Malignant Neoplasms in Adolescents and Young Adults With Cancer
Abstract
BACKGROUND:
The authors describe the incidence and characteristics of secondary malignant neoplasms (SMNs) in adolescent and young adult (AYA) cancer survivors compared with those in younger and older cancer survivors.
METHODS:
Children aged 14 years, AYAs aged 15 to 39, and older adults aged 40 years at the time of primary diagnosis who were reported as cancer survivors in the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2011 were compared in this population-based analysis. The primary analysis was the risk that an SMN would occur 5 years after the original diagnosis for patients who had the more common AYA cancers (leukemia, lymphoma, testicular malignancy, ovarian malignancy, melanoma, and cancers of the thyroid, breast, soft tissue, or bone). The standardized incidence ratio (SIR), absolute excess risk (AER), and cumulative incidence of SMN for the selected cancers were assessed. The risk of SMN for the entire cohort also was analyzed.
RESULTS:
Of the 148,558 AYA survivors who were diagnosed with a selected cancer, 7384 developed an SMN 5 years after their original diagnosis. The SIRs (95% confidence intervals [CIs]) were 1.58 (95% CI, 1.55-1.62) for AYAs, 4.26 (95% CI, 3.77-4.80) for children, and 1.10 (95% CI, 1.09-1.11) for older adults, and the AERs were 22.9, 16.6, and 14.7, respectively. The cumulative incidence of SMN at 30 years was 13.9% for the AYA group. The most common SMNs in AYAs were breast cancer, gastrointestinal cancer, genital cancers, and melanoma. AYAs who had received radiation therapy had a higher cumulative incidence of SMN.
CONCLUSIONS:
AYAs who survive cancer for more than 5 years have a higher relative risk of SMN compared with the general population and have a higher absolute risk of SMN compared with younger or older cancer survivors. Cancer 2016;122:116-23. VC 2015 American Cancer Society.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/26441212
Citation
Lee, Jean S., Steven G. Dubois, Peter F. Coccia, Archie Bleyer, Rebecca L. Olin, and Robert E. Goldsby. "Increased Risk of Second Malignant Neoplasms in Adolescents and Young Adults with Cancer." Cancer 122.1 (2015): 116-23.
BACKGROUND:
The authors describe the incidence and characteristics of secondary malignant neoplasms (SMNs) in adolescent and young adult (AYA) cancer survivors compared with those in younger and older cancer survivors.
METHODS:
Children aged 14 years, AYAs aged 15 to 39, and older adults aged 40 years at the time of primary diagnosis who were reported as cancer survivors in the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2011 were compared in this population-based analysis. The primary analysis was the risk that an SMN would occur 5 years after the original diagnosis for patients who had the more common AYA cancers (leukemia, lymphoma, testicular malignancy, ovarian malignancy, melanoma, and cancers of the thyroid, breast, soft tissue, or bone). The standardized incidence ratio (SIR), absolute excess risk (AER), and cumulative incidence of SMN for the selected cancers were assessed. The risk of SMN for the entire cohort also was analyzed.
RESULTS:
Of the 148,558 AYA survivors who were diagnosed with a selected cancer, 7384 developed an SMN 5 years after their original diagnosis. The SIRs (95% confidence intervals [CIs]) were 1.58 (95% CI, 1.55-1.62) for AYAs, 4.26 (95% CI, 3.77-4.80) for children, and 1.10 (95% CI, 1.09-1.11) for older adults, and the AERs were 22.9, 16.6, and 14.7, respectively. The cumulative incidence of SMN at 30 years was 13.9% for the AYA group. The most common SMNs in AYAs were breast cancer, gastrointestinal cancer, genital cancers, and melanoma. AYAs who had received radiation therapy had a higher cumulative incidence of SMN.
CONCLUSIONS:
AYAs who survive cancer for more than 5 years have a higher relative risk of SMN compared with the general population and have a higher absolute risk of SMN compared with younger or older cancer survivors. Cancer 2016;122:116-23. VC 2015 American Cancer Society.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/26441212
Citation
Lee, Jean S., Steven G. Dubois, Peter F. Coccia, Archie Bleyer, Rebecca L. Olin, and Robert E. Goldsby. "Increased Risk of Second Malignant Neoplasms in Adolescents and Young Adults with Cancer." Cancer 122.1 (2015): 116-23.
20. Infectious diseases in the first year of life, perinatal characteristics and childhood acute leukaemia
Abstract
“The objective of the present study was to investigate the role of early common infections and perinatal characteristics in the aetiology of childhood common leukaemia. A case–control study was conducted from 1995 to 1998 in France, and included 473 incident cases of acute leukaemia (AL) (408 acute lymphoblastic leukaemia (ALL), 65 acute myeloid leukaemia (AML) age-, sex- and regionmatched with 567 population-based controls. Data on the medical history of the child and his/her environment were collected using self-administered questionnaires. Analyses were conducted using nonconditional logistic regression. A slight negative association with early infections was observed (OR ¼ 0.8; 95% CI (0.6–1.0)). The association was stronger for early gastrointestinal infections. Early day-care was found to be associated with a decreased risk of AL (OR ¼ 0.6; 95% CI (0.4–0.8) and OR ¼ 0.8; 95% CI (0.5–1.2) for day-care starting before age 3 months and between 3 and 6 months, respectively). No association with breast-feeding was observed, irrespective of its duration. A birth order of 4 or more was associated with a significantly increased risk of AL (OR ¼ 2.0; 95% CI (1.1–3.7) with ALL). A history of asthma was associated with a decreased risk of ALL (OR 0.5; 95% CI (0.3–0.90). Although the results regarding birth order and breast-feeding do not fit with Greaves’ hypothesis, the study supports the hypothesis that early common infections may play a protective role in the aetiology of childhood leukaemia, although this effect was not more marked for common”
Link
https://www.ncbi.nlm.nih.gov/pubmed/14710221
Citation
Silva, N. Jourdan-Da, Y. Perel, F. Me´chinaud, E. Plouvier, V. Gandemer, P. Lutz, J. P. Vannier, J. L. Lamagne´re, G. Margueritte, P. Boutard, A. Robert, C. Armari, M. Munzer, F. Millot, L. De Lumley, C. Berthou, X. Rialland, B. Pautard, D. He´mon, and J. Clavel. "Infectious Diseases in the First Year of Life, Perinatal Characteristics and Childhood Acute Leukaemia." British Journal of Cancer 90.1 (2004): 139-45
“The objective of the present study was to investigate the role of early common infections and perinatal characteristics in the aetiology of childhood common leukaemia. A case–control study was conducted from 1995 to 1998 in France, and included 473 incident cases of acute leukaemia (AL) (408 acute lymphoblastic leukaemia (ALL), 65 acute myeloid leukaemia (AML) age-, sex- and regionmatched with 567 population-based controls. Data on the medical history of the child and his/her environment were collected using self-administered questionnaires. Analyses were conducted using nonconditional logistic regression. A slight negative association with early infections was observed (OR ¼ 0.8; 95% CI (0.6–1.0)). The association was stronger for early gastrointestinal infections. Early day-care was found to be associated with a decreased risk of AL (OR ¼ 0.6; 95% CI (0.4–0.8) and OR ¼ 0.8; 95% CI (0.5–1.2) for day-care starting before age 3 months and between 3 and 6 months, respectively). No association with breast-feeding was observed, irrespective of its duration. A birth order of 4 or more was associated with a significantly increased risk of AL (OR ¼ 2.0; 95% CI (1.1–3.7) with ALL). A history of asthma was associated with a decreased risk of ALL (OR 0.5; 95% CI (0.3–0.90). Although the results regarding birth order and breast-feeding do not fit with Greaves’ hypothesis, the study supports the hypothesis that early common infections may play a protective role in the aetiology of childhood leukaemia, although this effect was not more marked for common”
Link
https://www.ncbi.nlm.nih.gov/pubmed/14710221
Citation
Silva, N. Jourdan-Da, Y. Perel, F. Me´chinaud, E. Plouvier, V. Gandemer, P. Lutz, J. P. Vannier, J. L. Lamagne´re, G. Margueritte, P. Boutard, A. Robert, C. Armari, M. Munzer, F. Millot, L. De Lumley, C. Berthou, X. Rialland, B. Pautard, D. He´mon, and J. Clavel. "Infectious Diseases in the First Year of Life, Perinatal Characteristics and Childhood Acute Leukaemia." British Journal of Cancer 90.1 (2004): 139-45
21. Interaction of allergy history and antibodies to specific Varicella zoster virus proteins on glioma risk
Abstract
“Glioma is the most common cancer of the central nervous system but with few confirmed risk factors. Glioma has been inversely associated with chicken pox, shingles, and seroreactivity to varicella virus (VZV), as well as to allergies and allergy-associated IgE. The role of antibody reactivity against individual VZV antigens has not been assessed. Ten VZV-related proteins, selected for high immunogenicity or known function, were synthesized and used as targets for antibody measurements in the sera of 143 glioma cases and 131 healthy controls selected from the San Francisco Bay Area Adult Glioma Study. Glioma cases exhibited significantly reduced seroreactivity compared to controls for six antigens, including proteins IE63 (OR = 0.26, 95%CI: 0.12-0.58, comparing lowest quartile to highest), and the VZV-unique protein ORF2p (OR = 0.44, 95%CI:0.21-0.96, lowest quartile to highest). When stratifying the study population into those with low and high self-reported allergy history, VZV protein seroreactivity was only associated inversely with glioma among individuals self-reporting more than two allergies. The data provide insight into both allergy and VZV effects on glioma: strong anti-VZV reactions in highly allergic individuals is associated with reduced occurrence of glioma. This result suggests a role for specificity in the anti-VZV immunity in brain tumor suppression for both individual VZV antigens and in the fine-tuning of the immune response by allergy. Anti-VZV reactions may also be a biomarker of effective CNS immunosurveillance due to the tropism of the virus.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/24127236
Citation
Lee, Seung-Tae, Paige Bracci, Mi Zhou, Terri Rice, John Wiencke, Margaret Wrensch, and Joseph Wiemels. "Interaction of Allergy History and Antibodies to Specific Varicella-zoster Virus Proteins on Glioma Risk." International Journal of Cancer 134.9 (2013): 2199-210.
“Glioma is the most common cancer of the central nervous system but with few confirmed risk factors. Glioma has been inversely associated with chicken pox, shingles, and seroreactivity to varicella virus (VZV), as well as to allergies and allergy-associated IgE. The role of antibody reactivity against individual VZV antigens has not been assessed. Ten VZV-related proteins, selected for high immunogenicity or known function, were synthesized and used as targets for antibody measurements in the sera of 143 glioma cases and 131 healthy controls selected from the San Francisco Bay Area Adult Glioma Study. Glioma cases exhibited significantly reduced seroreactivity compared to controls for six antigens, including proteins IE63 (OR = 0.26, 95%CI: 0.12-0.58, comparing lowest quartile to highest), and the VZV-unique protein ORF2p (OR = 0.44, 95%CI:0.21-0.96, lowest quartile to highest). When stratifying the study population into those with low and high self-reported allergy history, VZV protein seroreactivity was only associated inversely with glioma among individuals self-reporting more than two allergies. The data provide insight into both allergy and VZV effects on glioma: strong anti-VZV reactions in highly allergic individuals is associated with reduced occurrence of glioma. This result suggests a role for specificity in the anti-VZV immunity in brain tumor suppression for both individual VZV antigens and in the fine-tuning of the immune response by allergy. Anti-VZV reactions may also be a biomarker of effective CNS immunosurveillance due to the tropism of the virus.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/24127236
Citation
Lee, Seung-Tae, Paige Bracci, Mi Zhou, Terri Rice, John Wiencke, Margaret Wrensch, and Joseph Wiemels. "Interaction of Allergy History and Antibodies to Specific Varicella-zoster Virus Proteins on Glioma Risk." International Journal of Cancer 134.9 (2013): 2199-210.
22. Measles virus causes immunogenic cell death in human melanoma
Abstract
“Oncolytic viruses (OV) are promising treatments for cancer, with several currently undergoing testing in randomised clinical trials. Measles virus (MV) has not yet been tested in models of human melanoma. This study demonstrates the efficacy of MV against human melanoma. It is increasingly recognised that an essential component of therapy with OV is the recruitment of host anti-tumour immune responses, both innate and adaptive. MV-mediated melanoma cell death is an inflammatory process, causing the release of inflammatory cytokines including type-1 interferons and the potent danger signal HMGB1. Here, using human in vitro models, we demonstrate that MV enhances innate antitumour activity, and that MV-mediated melanoma cell death is capable of stimulating a melanoma-specific adaptive immune response.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/22170342
Citation
Donnelly, O. G., F. Errington-Mais, L. Steele, E. Hadac, V. Jennings, K. Scott, H. Peach, R. M. Phillips, J. Bond, H. Pandha, K. Harrington, R. Vile, S. Russell, P. Selby, and A. A. Melcher. "Measles Virus Causes Immunogenic Cell Death in Human Melanoma." Gene Therapy 20.1 (2011): 7-15.
“Oncolytic viruses (OV) are promising treatments for cancer, with several currently undergoing testing in randomised clinical trials. Measles virus (MV) has not yet been tested in models of human melanoma. This study demonstrates the efficacy of MV against human melanoma. It is increasingly recognised that an essential component of therapy with OV is the recruitment of host anti-tumour immune responses, both innate and adaptive. MV-mediated melanoma cell death is an inflammatory process, causing the release of inflammatory cytokines including type-1 interferons and the potent danger signal HMGB1. Here, using human in vitro models, we demonstrate that MV enhances innate antitumour activity, and that MV-mediated melanoma cell death is capable of stimulating a melanoma-specific adaptive immune response.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/22170342
Citation
Donnelly, O. G., F. Errington-Mais, L. Steele, E. Hadac, V. Jennings, K. Scott, H. Peach, R. M. Phillips, J. Bond, H. Pandha, K. Harrington, R. Vile, S. Russell, P. Selby, and A. A. Melcher. "Measles Virus Causes Immunogenic Cell Death in Human Melanoma." Gene Therapy 20.1 (2011): 7-15.
23. Measles virus for cancer therapy
Abstract
“Measles virus offers an ideal platform from which to build a new generation of safe, effective oncolytic viruses. Occasional "spontaneous" tumor regressions have occurred during natural measles infections, but common tumors do not express SLAM, the wild-type MV receptor, and are therefore not susceptible to the virus. Serendipitously, attenuated vaccine strains of measles virus have adapted to use CD46, a regulator of complement activation that is expressed in higher abundance on human tumor cells than on their non transformed counterparts. For this reason, attenuated measles viruses are potent and selective oncolytic agents showing impressive antitumor activity in mouse xenograft models. The viruses can be engineered to enhance their tumor specificity, increase their antitumor potency and facilitate noninvasive in vivo monitoring of their spread. A major impediment to the successful deployment of oncolytic measles viruses as anticancer agents is the high prevalence of pre-existing anti measles immunity, which impedes bloodstream delivery and curtails intratumoral virus spread. It is hoped that these problems can be addressed by delivering the virus inside measles-infected cell carriers and/or by concomitant administration of immunosuppressive drugs. From a safety perspective, population immunity provides an excellent defense against measles spread from patient to carers and, in fifty years of human experience, reversion of attenuated measles to a wild type pathogenic phenotype has not been observed. Clinical trials testing oncolytic measles viruses as an experimental cancer therapy are currently underway.”
Link
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926122/
Citation
Russell, S. J., and K. W. Peng. "Measles Virus for Cancer Therapy." Current Topics in Microbiology and Immunology Measles (n.d.): 213-41.
“Measles virus offers an ideal platform from which to build a new generation of safe, effective oncolytic viruses. Occasional "spontaneous" tumor regressions have occurred during natural measles infections, but common tumors do not express SLAM, the wild-type MV receptor, and are therefore not susceptible to the virus. Serendipitously, attenuated vaccine strains of measles virus have adapted to use CD46, a regulator of complement activation that is expressed in higher abundance on human tumor cells than on their non transformed counterparts. For this reason, attenuated measles viruses are potent and selective oncolytic agents showing impressive antitumor activity in mouse xenograft models. The viruses can be engineered to enhance their tumor specificity, increase their antitumor potency and facilitate noninvasive in vivo monitoring of their spread. A major impediment to the successful deployment of oncolytic measles viruses as anticancer agents is the high prevalence of pre-existing anti measles immunity, which impedes bloodstream delivery and curtails intratumoral virus spread. It is hoped that these problems can be addressed by delivering the virus inside measles-infected cell carriers and/or by concomitant administration of immunosuppressive drugs. From a safety perspective, population immunity provides an excellent defense against measles spread from patient to carers and, in fifty years of human experience, reversion of attenuated measles to a wild type pathogenic phenotype has not been observed. Clinical trials testing oncolytic measles viruses as an experimental cancer therapy are currently underway.”
Link
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926122/
Citation
Russell, S. J., and K. W. Peng. "Measles Virus for Cancer Therapy." Current Topics in Microbiology and Immunology Measles (n.d.): 213-41.