Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Ann Med. 2023 Dec;55(1):62-71. doi: 10.1080/07853890.2022.2146743.
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 or early life exposures on adulthood gastrointestinal cancer, especially for those with a high genetic risk.
目前有关出生体重和遗传因素与胃肠道癌之间关联的流行病学研究仍然较少。本研究旨在前瞻性评估出生体重和遗传风险水平对成年后胃肠道癌发病的相互作用和联合效应。
本研究共纳入英国生物库研究中的 254997 名参与者。我们使用多元受限立方样条和 Cox 回归模型来估计出生体重与胃肠道癌风险之间的关联的风险比（HR）和 95%置信区间（CI），然后构建多基因风险评分（PRS）来评估其与出生体重对胃肠道癌发展的相互作用和联合效应。
在中位随访 8.88 年期间，我们记录了 2512 例发病病例。与报告正常出生体重（2.5-4.5kg）的参与者相比，出生体重较高（≥4.5kg）的参与者患胃肠道癌的多变量调整 HR 为 1.17（95%CI：1.01-1.36）。这种关联在胰腺癌中表现得尤为明显，HR 为 1.82（95%CI：1.26-2.64）。低出生体重与胃肠道癌之间无统计学显著关联。出生体重较高且 PRS 较高的参与者患胃肠道癌的风险最高（HR：2.95，95%CI：2.19-3.96）。
我们的研究结果强调，高出生体重与胃肠道癌的发病率较高相关，特别是胰腺癌。通过控制出生体重，特别是对于遗传风险较高的个体，可能会获得益处。
