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Male Sex and the Risk of Childhood Cancer: The Mediating Effect of Birth Defects.

ABSTRACT: Background:There is a persistent, unexplained disparity in sex ratio among childhood cancer cases, whereby males are more likely to develop most cancers. This male predominance is also seen for most birth defects, which are strongly associated with risk of childhood cancer. We conducted mediation analysis to estimate whether the increased risk of cancer among males is partially explained by birth defect status. Methods:We used a population-based birth cohort with linked data from birth certificates, birth defects registries, and cancer registries from Arkansas, Michigan, North Carolina, and Texas. We conducted counterfactual mediation analysis to estimate the natural direct and indirect effects of sex on cancer risk, modeling birth defect status as mediator. State; birth year; plurality; and maternal race and ethnicity, age, and education were considered confounders. We conducted separate analyses limited to cancers diagnosed younger than 1?year of age. Results:Our dataset included 10 181 074 children: 15 110 diagnosed with cancer, 539 567 diagnosed with birth defects, and 2124 co-occurring cases. Birth defect status mediated 38% of the association between sex and cancer overall. The proportion mediated varied by cancer type, including acute myeloid leukemia (93%), neuroblastoma (35%), and non-Hodgkin lymphoma (6%). Among children younger than 1?year of age at cancer diagnosis, the proportion mediated was substantially higher (82%). Conclusions:Our results suggest that birth defects mediate a statistically significant proportion of the relationship between sex and childhood cancer. The proportion mediated varied by cancer type and diagnosis age. These findings improve our understanding of the causal pathway underlying male sex as a risk factor for childhood cancer.

SUBMITTER: Marcotte EL

PROVIDER: S-EPMC7583156 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Male Sex and the Risk of Childhood Cancer: The Mediating Effect of Birth Defects.

Marcotte Erin L EL Schraw Jeremy M JM Desrosiers Tania A TA Nembhard Wendy N WN Langlois Peter H PH Canfield Mark A MA Meyer Robert E RE Plon Sharon E SE Lupo Philip J PJ

JNCI cancer spectrum 20200611 5

<h4>Background</h4>There is a persistent, unexplained disparity in sex ratio among childhood cancer cases, whereby males are more likely to develop most cancers. This male predominance is also seen for most birth defects, which are strongly associated with risk of childhood cancer. We conducted mediation analysis to estimate whether the increased risk of cancer among males is partially explained by birth defect status.<h4>Methods</h4>We used a population-based birth cohort with linked data from ...[more]

PMID: 33134832

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Project description:BackgroundBirth defects are established risk factors for childhood cancer. Nonetheless, cancer epidemiology in children with birth defects is not well characterized.MethodsUsing data from population-based registries in 4 US states, this study compared children with cancer but no birth defects (n = 13,111) with children with cancer and 1 or more nonsyndromic birth defects (n = 1616). The objective was to evaluate cancer diagnostic characteristics, including tumor type, age at diagnosis, and stage at diagnosis.ResultsCompared with the general population of children with cancer, children with birth defects were diagnosed with more embryonal tumors (26.6% vs 18.7%; q < 0.001), including neuroblastoma (12.5% vs 8.2%; q < 0.001) and hepatoblastoma (5.0% vs 1.3%; q < 0.001), but fewer hematologic malignancies, including acute lymphoblastic leukemia (12.4% vs 24.4%; q < 0.001). In age-stratified analyses, differences in tumor type were evident among children younger than 1 year and children 1 to 4 years old, but they were attenuated among children 5 years of age or older. The age at diagnosis was younger in children with birth defects for most cancers, including leukemia, lymphoma, astrocytoma, medulloblastoma, ependymoma, embryonal tumors, and germ cell tumors (all q < 0.05).ConclusionsThe results indicate possible etiologic heterogeneity in children with birth defects, have implications for future surveillance efforts, and raise the possibility of differential cancer ascertainment in children with birth defects.Lay summaryScientific studies suggest that children with birth defects are at increased risk for cancer. However, these studies have not been able to determine whether important tumor characteristics, such as the type of tumor diagnosed, the age at which the tumor is diagnosed, and the degree to which the tumor has spread at the time of diagnosis, are different for children with birth defects and children without birth defects. This study attempts to answer these important questions. By doing so, it may help scientists and physicians to understand the causes of cancer in children with birth defects and diagnose cancer at earlier stages when it is more treatable.

Project description:BACKGROUND:The objective of the current study was to characterize and identify factors associated with perceptions of risk of infertility among adult male survivors of childhood cancer. METHODS:A total of 1233 adult male survivors from the Childhood Cancer Survivor Study who were without a history of disease recurrence or subsequent malignancy reported their perceptions of their risk of infertility compared with men never diagnosed with cancer. Survivors were a median age of 37.8 years (range, 22.0-58.7 years) and were 28.4 years from their diagnosis (range, 21.4-39.2 years). Multivariable logistic regression evaluated factors associated with perceptions of risk. RESULTS:Overall, 35.9% of the survivors (443 of 1233 survivors) reported perceptions of their risk of infertility that were discordant with their actual risk based on previous cancer treatment exposures. Discordant perceptions were equally common among men exposed to gonadotoxic therapies (36.3%; 311 of 857 men) and those with no history of gonadotoxic exposure (35.1%; 132 of 376 men). Survivors who fathered children (odds ratio [OR], 4.14; 95% confidence interval [95% CI], 2.74-6.24), had no survivor-focused health care (OR, 3.07; 95% CI, 1.57-5.99), were nonwhite (OR, 2.28; 95% CI, 1.10-4.75), and were of lower income were more likely to report no increased risk of infertility after gonadotoxic treatment. Perceptions of increased risk of infertility among men with no history of gonadotoxic treatment were predicted by never having fathered a child (OR, 1.88; 95% CI, 1.17-3.03), recent participation in survivor-focused health care (OR, 2.11; 95% CI, 1.01-4.42), and higher educational achievement. CONCLUSIONS:Many male survivors of childhood cancer are unaware of how their cancer treatments could impact their reproductive health, underscoring the need for all patients to receive education regarding their risk of infertility throughout the continuum of cancer care. Cancer 2018;124:2447-55. © 2018 American Cancer Society.

Dataset Information

Male Sex and the Risk of Childhood Cancer: The Mediating Effect of Birth Defects.

Publications

Male Sex and the Risk of Childhood Cancer: The Mediating Effect of Birth Defects.

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