Birthweight, genetic risk, and gastrointestinal cancer incidence: a prospective cohort study
Creators: name: Long, Lu
name: He, Heng
name: Shen, Qian
name: Peng, Hongxia
name: Zhou, Xiaorui
name: Wang, Haoxue
name: Zhang, Shanshan
name: Qin, Shifan
name: Lu, Zequn
name: Zhu, Ying
name: Tian, Jianbo
name: Chang, Jiang
name: Miao, Xiaoping
name: Shen, Na
name: Zhong, Rong
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Neuroscience
subject: Pharmacology
subject: Biotechnology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Developmental Biology
subject: Cancer
subject: Mental Health
subject: Virology

description: 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. 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. 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). Our findings highlight that high birthweight is associated with a higher incidence of gastrointestinal cancer, especially for pancreatic cancer. Benefits would be obtained from birthweight control, particularly for individuals with a high genetic risk.KEY MESSAGESThe epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce.This cohort study of 254,997 adults in the United Kingdom found an association of high birthweight with the incidence of gastrointestinal cancer, especially for pancreatic cancer, and also found that participants with high birthweight and high polygenic risk score had the highest risk of gastrointestinal cancer.Our data suggests a possible effect of <i>in utero</i> or early life exposures on adulthood gastrointestinal cancer, especially for those with a high genetic risk. The epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce. This cohort study of 254,997 adults in the United Kingdom found an association of high birthweight with the incidence of gastrointestinal cancer, especially for pancreatic cancer, and also found that participants with high birthweight and high polygenic risk score had the highest risk of gastrointestinal cancer. Our data suggests a possible effect of <i>in utero</i> or early life exposures on adulthood gastrointestinal cancer, especially for those with a high genetic risk.