Among 615 tested individuals, pathogenic variant incidence was higher in black (58.6%) and mixed populations (58.8%) compared with Asian (42.9%) and American Indian (33.3%) participants.
Cross-Sectional (n=1,603)
Do environmental, behavioral, and medical history factors influence cancer risk in individuals with or without hereditary cancer gene variants?
Environmental, behavioral, and medical history factors may influence cancer risk in individuals with pathogenic variants, suggesting increased environmental susceptibility in PV carriers.
Abstract Background: Individuals with genetic cancer predisposition have higher risks of cancer. However, the role of lifestyle, environmental factors, and health history in modifying cancer risk in these individuals is not well defined. The eGene study was designed to address this gap by utilizing large-scale self-reported data. Methods: The 216-item eGene questionnaire was used to assess environmental, behavioral, and medical history factors that may influence cancer risk among individuals with or without hereditary cancer gene variants. Participants were recruited through Eureka and MyChart. To assess the association between each factor and cancer risk, Odds Ratios (OR) with 95% Confidence Intervals (CI) obtained by univariable logistic regression models were reported. Results: Among all 1603 participants, the median age was 52, 68% were females, 82% were white, 27% had a personal history of cancer, and 60.5% had a family history of cancer. Among 615 individuals who had genetic testing, 354 tested positive for a pathogenic variant (PV) and 185 tested negative. For PV carriers, 60% never had cancer, 19% had breast cancer history, 5.4% had non-melanoma skin cancer history, and 3.8% had prostate cancer history. For no PV carriers, 62% never had cancer, 14% had breast cancer history and 3.4% had prostate cancer. PV incidence rate was higher in black (58.6%) and mixed populations (58.8%) compared with Asian (42.9%) and American Indian (33.3%). The most common PVs in both cancer cases and controls were in BRCA1, BRCA2 and ATM genes. Table 1 summarizes the list of variables statistically significantly associated with cancer incidence within PV carriers and no PV carriers. Conclusion: These findings suggest increased environmental susceptibility in PV carriers. Ongoing analyses will further examine associations between medical, lifestyle, and environmental factors and cancer incidence in the general population in a multivariable fashion and explore possible gene-environmental interactions. Citation Format: Zhengwei Zhang, Lou Romanens-Renard, Li Zhang, Pamela N. Munster, . Determinants of Cancer Risk in Hereditary Cancer-Prone Individuals: The eGene Study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6277.
Zhang et al. (2026) conducted a cross-sectional in Hereditary cancer predisposition (n=1,603). Pathogenic variant (PV) carrier status vs. No PV carriers was evaluated on Cancer incidence. Among 615 tested individuals, pathogenic variant incidence was higher in black (58.6%) and mixed populations (58.8%) compared with Asian (42.9%) and American Indian (33.3%) participants.