Selection bias as an explanation for the observed protective association of childhood adiposity with breast cancer

Abstract

Objectives: Recalled childhood adiposity is inversely associated with breast cancer observationally, including in Mendelian randomization (MR) studies. Breast cancer studies recruited in adulthood only include survivors of childhood adiposity and breast cancer or a competing risk. We assessed recalled childhood adiposity on participant reported sibling and maternal breast cancer to ensure ascertainment of nonsurvivors. Study Design and Setting: We obtained independent strong genetic predictors of recalled childhood adiposity for women and their associations with participant reported own, sibling and maternal breast cancer from UK Biobank genome wide association studies. Results: Recalled childhood adiposity in women was inversely associated with own breast cancer using Mendelian randomization inverse variance weighting (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.52–0.84) but less clearly related to participant reported sibling (OR 0.89, 95% CI 0.69–1.14) or maternal breast cancer (OR 0.84, 95% CI 0.67–1.05). Conclusion: Weaker inverse associations of recalled childhood adiposity with breast cancer with more comprehensive ascertainment of cases before recruitment suggests the inverse association of recalled childhood adiposity with breast cancer could be partly selection bias from preferential selection of survivors. Greater consideration of survival bias in public health relevant causal inferences would be helpful.