A Mendelian randomization analysis of circulating lipid traits and breast cancer risk
A Mendelian randomization analysis of circulating lipid traits and breast cancer risk
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DOI：
10.1093/ije/dyz242
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发表时间：
2020-08-01
影响因子：
7.7
通讯作者：
Zheng, Wei
中科院分区：
文献类型：
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作者：
Beeghly-Fadiel, Alicia;Khankari, Nikhil K.;Zheng, Wei
背景：传统的流行病学研究评估了循环脂质水平与乳腺癌风险之间的关联，但结果不一致。由于孟德尔随机化分析可能为因果推断提供证据，因此我们试图评估乳腺癌风险与四种遗传预测的脂质特征之间潜在的无偏关联。方法：之前的全基因组关联研究 (GWAS) 已鉴定出与高密度脂蛋白胆固醇 (HDL-C)、低密度脂蛋白胆固醇 (LDL-C)、甘油三酯和总胆固醇相关的 164 个离散变异。我们使用其中的 162 个独特变异来构建来自乳腺癌协会联盟 (BCAC) 的总共 101 424 例乳腺癌病例和 80 253 例欧洲血统对照的加权遗传评分 (wGS)。使用无条件逻辑回归来估计比值比 (OR) 和 95% 置信区间 (CI)，以了解基因预测的脂质特征的每个标准差增加与乳腺癌风险之间的关联。还进行了其他孟德尔随机分析方法和敏感性分析，以评估多效性和仪器有效性。结果：对应于约 15 mg/dL，基因预测 HDL-C 增加 1 个标准差与乳腺癌风险增加 12% 相关（OR：1.12，95% CI：1.08-1.16）。在调整乳腺癌危险因素后，结果是一致的，并且在多项敏感性分析中也是稳健的。与基因预测的甘油三酯和总胆固醇的关联不一致，并且没有观察到与基因预测的 LDL-C 的关联。结论：这项研究提供了强有力的证据，表明循环 HDL-C 可能与乳腺癌风险增加相关，而 LDL-C 可能与乳腺癌风险无关。
Background: Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits.Methods: Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity.Results: Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08-1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed.Conclusions: This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk.