Abstract PR03: Sex ratio disparities and the risk of childhood cancer: Evaluating the mediating effect of birth defects among 15,000 childhood cancer cases
Bibliographic record
Abstract
Abstract Background: There is a persistent yet unexplained disparity in the sex ratio among childhood cancer cases, whereby males are more likely to develop several cancers. These patterns are also seen for most birth defects, which are strongly associated with the risk of childhood cancer. We conducted a mediation analysis to estimate whether birth defect status mediates the association between sex and childhood cancer risk. Methods: We linked data from birth, birth defects, and cancer registries to obtain a population-based birth cohort including births from 1992-2013 in Arkansas, Michigan, North Carolina, and Texas. We obtained birth defects diagnoses, including chromosomal and nonchromosomal defects, from statewide, population-based birth defects registries. We focused on “major” defects as defined by the National Birth Defects Prevention Network and the National Birth Defects Prevention Study. Cancer diagnoses that occurred prior to age 18 years were obtained from state cancer registries. We obtained data on child’s sex, birth weight, gestational age, maternal race/ethnicity, maternal age, and plurality from birth records. We conducted counterfactual mediation analysis to estimate the direct and indirect effects of sex on risk of childhood cancer, modeling sex as the exposure, birth defect status as the mediator, and cancer type as the outcome. State, maternal race/ethnicity (white, black, other), maternal age (continuous), and plurality (singleton vs. multiple) were considered potential mediator-outcome confounders. Due to lower success rates of linkage to birth records among adolescent cancer cases, we conducted a sensitivity analysis limiting to cancers diagnosed at age < 5 years. Results: Our dataset included 10,181,074 children (5,208,379 males; 4,972,695 females), including 15,110 with cancer diagnoses (8044 males; 7066 females), 539,567 children with birth defects diagnoses (320,666 males; 218,901 females), and 2,124 co-occurring cases (children with both cancer and one or more birth defect diagnosis: 1,186 males; 938 females). We observed mediation of the association between sex and childhood cancer overall by birth defect status (proportion mediated [PM]: 38%). In analyses of specific cancer types, we observed variation of the estimated proportion mediated among several cancers, including hepatoblastoma (PM: 33%), neuroblastoma (PM: 35%), non-Hodgkin lymphoma (PM: 6%), and soft tissue sarcomas (PM: 25%). In analysis of children age < 5 years at cancer diagnosis, we observed similar results. Conclusions: Our results suggest that birth defects mediate a significant proportion of the overall relationship between sex and childhood cancer. While approximately 60% of the male excess in childhood cancer cases remains unexplained, these findings add to our understanding of the causal pathway of male sex as a risk factor for childhood cancer. Additional studies are under way to characterize the biology underlying these observations. This abstract is also being presented as Poster A66. Citation Format: Erin L. Marcotte, Jeremy M. Schraw, Tania A. Desrosiers, Wendy N. Nembhard, Peter H. Langlois, Mark A. Canfield, Robert E. Meyer, Sharon E. Plon, Philip Lupo. Sex ratio disparities and the risk of childhood cancer: Evaluating the mediating effect of birth defects among 15,000 childhood cancer cases [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR03.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.035 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.005 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.010 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".