Schooling C Mary, Fei Kezhen, Zhao Jie V
Environmental, Occupational, and Geospatial Health Sciences, CUNY School of Public Health, 55 West 125th St, New York, NY 10027, USA; School of Public Health, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong, China.
Environmental, Occupational, and Geospatial Health Sciences, CUNY School of Public Health, 55 West 125th St, New York, NY 10027, USA.
J Clin Epidemiol. 2023 Dec;164:104-111. doi: 10.1016/j.jclinepi.2023.09.015. Epub 2023 Sep 30.
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.
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.
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).
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.
回顾性童年肥胖与乳腺癌之间存在反向关联，这在观察性研究中已得到证实，包括孟德尔随机化（MR）研究。仅在成年期招募的乳腺癌研究仅纳入了童年肥胖和乳腺癌的幸存者或存在竞争风险的人群。我们评估了参与者报告的兄弟姐妹和母亲的乳腺癌与回顾性童年肥胖之间的关系，以确保纳入非幸存者。
我们从英国生物银行全基因组关联研究中获得了女性回顾性童年肥胖的独立强遗传预测因子，以及它们与参与者报告的自身、兄弟姐妹和母亲患乳腺癌之间的关联。
使用孟德尔随机化逆方差加权法，女性回顾性童年肥胖与自身患乳腺癌呈反向关联（优势比（OR）为0.66，95%置信区间（CI）为0.52 - 0.84），但与参与者报告的兄弟姐妹患乳腺癌（OR为0.89，95% CI为0.69 - 1.14）或母亲患乳腺癌（OR为0.84，95% CI为0.67 - 1.05）的相关性较弱。
在招募前更全面地确定病例时，回顾性童年肥胖与乳腺癌之间的反向关联较弱，这表明回顾性童年肥胖与乳腺癌之间的反向关联可能部分是由于幸存者的优先选择导致的选择偏倚。在与公共卫生相关的因果推断中更多地考虑生存偏倚将有所帮助。
