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

Objective: Recalled childhood adiposity is inversely associated with breast cancer observationally, including in Mendelian randomization (MR) studies, questioning its role. Breast cancer studies recruited in adulthood only include survivors of childhood adiposity and breast cancer. We assessed recalled childhood adiposity on participant reported sibling and maternal breast cancer to ensure ascertainment of non-survivors using MR. 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 (GWAS). We obtained MR inverse variance weighting estimates. Results: Childhood adiposity in women was inversely associated with own breast cancer (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.52 to 0.84) but unrelated to participant reported sibling (OR 0.85, 95% CI 0.60 to 1.20) or maternal breast cancer (OR 0.84, 95% CI 0.67 to 1.05 respectively). 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 is due to selection bias arising from preferential selection of survivors. Greater consideration of left truncation in public health relevant causal inferences is warranted.