Is birthweight associated with total and aggressive/lethal prostate cancer risks A systematic review and meta-analysis

Background:It has been hypothesised that intrauterine exposures are important for subsequent prostate cancer risk. Prior epidemiological studies have used birthweight as a proxy of cumulative intrauterine exposures to test this hypothesis, but results have been inconsistent partly because of limited statistical power.Methods:We investigated birthweight in relation to prostate cancer in the Medical Research Council (MRC) National Survey of Health and Development (NSHD) using Cox proportional hazards models. We then conducted a meta-analysis of birthweight in relation to total and aggressive/lethal prostate cancer risks, combining results from the NSHD analysis with 13 additional studies on this relationship identified from a systematic search in four major scientific literature databases through January 2015.Results:Random-effects models found that per kg increase in birthweight was positively associated with total (OR=1.02, 95% confidence interval (95% CI)=1.00, 1.05; I 2 =13%) and aggressive/lethal prostate cancer (OR=1.08, 95% CI=0.99, 1.19; I 2 =40%). Sensitivity analyses restricted to studies with birthweight extracted from medical records demonstrated stronger positive associations with total (OR=1.11, 95% CI=1.03, 1.19; I 2 =0%) and aggressive/lethal (OR=1.37, 95% CI=1.09, 1.74; I 2 =0%) prostate cancer. These studies heavily overlapped with those based in Nordic countries.Conclusions:This study provides evidence that heavier birthweight may be associated with modest increased risks of total and aggressive/lethal prostate cancer, which supports the hypothesis that intrauterine exposures may be related to subsequent prostate cancer risks.