Birthweight, genetic risk, and gastrointestinal cancer incidence: a prospective cohort study

作者：Lü Long, Heng He, Qian Shen, Hongxia Peng, Xiaorui Zhou, Haoxue Wang, Shanshan Zhang, Shifan Qin, Zequn Lu, Ying Zhu, Jianbo Tian, Jiang Chang, Xiaoping Miao, Na Shen, Rong Zhong · 发表于：Annals of Medicine · 年份：2022 · DOI：10.1080/07853890.2022.2146743 · 被引用次数：4 · 研究领域：Birth, Development, and Health、Gestational Diabetes Research and Management、Cancer Risks and Factors

Background The epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce. The study aimed to prospectively assess the interactions and joint effects of birthweight and genetic risk levels on gastrointestinal cancer incidence in adulthood.Methods A total of 254,997 participants were included in the UK Biobank study. We used multivariate restricted cubic splines and Cox regression models to estimate the hazard ratios (HRs) and 95% confidential intervals (CI) for the association between birthweight and gastrointestinal cancer risk, then constructed a polygenic risk score (PRS) to assess its interaction and joint effect with birthweight on the development of gastrointestinal cancer.Results We documented 2512 incident cases during a median follow-up of 8.88 years. Compare with participants reporting a normal birthweight (2.5–4.5 kg), multivariable-adjusted HR of gastrointestinal cancer incidence for participants with high birthweight (≥4.5 kg) was 1.17 (95%CI: 1.01–1.36). Such association was remarkably observed in pancreatic cancer, with an HR of 1.82 (95%CI: 1.26–2.64). No statistically significant association was observed between low birth weight and gastrointestinal cancers. Participants with high birthweight and high PRS had the highest risk of gastrointestinal cancer (HR: 2.95, 95%CI: 2.19–3.96).Conclusion Our findings highlight that high birthweight is associated with a higher incidence of gastrointesti...