Causal association of childhood obesity with cancer risk in adulthood: A Mendelian randomization study
Xuexian Fang, Xinhui Wang, Zijun Song, Dan Han, Xiangju Yin, Bingqing Liu, Luyi Chen, Ronghua Zhang, Fuzhi Lian, Xinbing Sui
Abstract
Abstract In observational studies of children and adolescents, higher body weight has been associated with distinct disease outcomes, including cancer, in adulthood. Therefore, we performed a two‐sample Mendelian randomization (MR) study to evaluate the causal effect of childhood obesity on long‐term cancer risk. Single‐nucleotide polymorphisms associated with higher childhood body mass index (BMI) from large‐scale genome‐wide association studies were used as genetic instruments. Summary‐level data for 24 site‐specific cancers were obtained from UK Biobank. We found that a 1‐SD increase in childhood BMI (kg/m 2 ) was significantly associated with a 60% increase in risk of pancreatic cancer (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.12‐2.28; P < 0.01) and a 47% increase in risk of esophageal cancer (OR: 1.47; 95% CI: 1.09‐1.97; P < 0.01) in adults. In contrast, there was an inverse association of genetic predisposition to childhood obesity with throat (OR: 0.46; 95% CI: 0.27‐0.79; P < 0.01) and breast cancer (OR: 0.77; 95% CI: 0.64‐0.94; P < 0.01) in adult life. For the other 20 cancers studied, no statistically significant association was observed. Our MR analyses found causal effects of childhood obesity on several cancers. Maintaining a healthy weight should be emphasized during childhood and adolescence to prevent cancer risk later in life.