Association of birth weight with cancer risk: a dose-response meta-analysis and Mendelian randomization study

Background Several articles have shown that birth weight is associated with the risk of many types of cancers. However, the results are inconsistent, and whether the relationship has a causal effect remains unknown. Methods We searched the PubMed and Embase libraries up to March 2021 and selected observational studies reporting the relationship between birth weight and adult-onset cancer risk. Dose-response meta-analysis and two-sample Mendelian randomization (MR) analysis were used to estimate the effect. Result In our dose-response meta-analysis, six cancers from 46 studies were found to have significant associations with birth weight. (Ovarian cancer: RR: 1.21, 95% CI 1.01-1.44; breast cancer: RR: 1.12, 95% CI 1.08-1.16; colorectal cancer: RR: 1.20, 95% CI 1.01-1.43; endometrial cancer: RR: 0.85, 95% CI 0.78-0.93; prostate cancer: RR: 1.27, 95% CI 1.01-1.61; testicular cancer: RR: 1.21, 95% CI 1.03-1.43). As birth weight increased, the slope of the dose-response curve of breast cancer increased continuously, and the curve of testicular cancer was U-shaped. In the MR study, seven cancers were included. Only invasive mucinous ovarian cancer was found to have a causal effect on birth weight (OR: 0.62; 95% CI 0.39-0.97), while other cancers did not. Conclusions Our findings suggest that birth weight are unlikely to have a casual effect on risk of cancers via the MR analysis, although the dose-response meta-analysis shows that there is a nonlinear relationship between birth weight and breast cancer and testicular cancer. More relevant researches are needed to further investigate their effect.