Abstract：
OBJECTIVE: 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.
METHODS: 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).
CONCLUSIONS: 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.
METHODS: 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).
CONCLUSIONS: 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.
摘要：
目的：回顾儿童肥胖与乳腺癌呈负相关，包括孟德尔随机化（MR）研究。在成年期招募的乳腺癌研究仅包括儿童肥胖和乳腺癌或竞争风险的幸存者。我们评估了参与者报告的兄弟姐妹和母亲乳腺癌的召回儿童肥胖，以确保确定非幸存者。
方法：我们获得了女性召回的儿童期肥胖的独立强遗传预测因子及其与参与者报告的关联，来自英国生物银行全基因组关联研究(GWAS)的兄弟姐妹和母亲乳腺癌。
结果：使用MR逆方差加权（比值比（OR）0.66，95％置信区间（CI）0.52至0.84），女性儿童肥胖与自身乳腺癌呈负相关，但与参与者报告的同胞（OR0.85，95％CI0.60至1.20）或母体乳腺癌（OR0.84，95％CI0.67至1.05）的相关性较低。
结论：在招募前更全面地确定病例的情况下，召回的儿童肥胖与乳腺癌的负相关较弱，这表明召回的儿童肥胖与乳腺癌的负相关可能是部分选择偏向于优先选择幸存者。在公共卫生相关的因果推断中更多地考虑生存偏差将是有帮助的。
方法：我们获得了女性召回的儿童期肥胖的独立强遗传预测因子及其与参与者报告的关联，来自英国生物银行全基因组关联研究(GWAS)的兄弟姐妹和母亲乳腺癌。
结果：使用MR逆方差加权（比值比（OR）0.66，95％置信区间（CI）0.52至0.84），女性儿童肥胖与自身乳腺癌呈负相关，但与参与者报告的同胞（OR0.85，95％CI0.60至1.20）或母体乳腺癌（OR0.84，95％CI0.67至1.05）的相关性较低。
结论：在招募前更全面地确定病例的情况下，召回的儿童肥胖与乳腺癌的负相关较弱，这表明召回的儿童肥胖与乳腺癌的负相关可能是部分选择偏向于优先选择幸存者。在公共卫生相关的因果推断中更多地考虑生存偏差将是有帮助的。
