Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
PLoS One. 2021 Jan 19;16(1):e0236904. doi: 10.1371/journal.pone.0236904. eCollection 2021.
Observational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer.
We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations.
One cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80-1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR = 0.90, 95% CI: 0.79-1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75-1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80-1.25), weighted median (OR: 0.97, 95% CI: 0.89-1.05) and weighted mode (OR: 1.00, CI: 0.93-1.07).
The results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak association.
观察性研究报告称，咖啡摄入量与乳腺癌风险之间要么没有关联，要么关联较弱。
我们使用来自英国生物库 212119 名具有白种人血统的女性参与者的全基因组关联（GWA）研究中与咖啡摄入相关的 33 个单核苷酸多态性（SNP）进行了两样本孟德尔随机化（MR）分析，以评估咖啡摄入与乳腺癌风险之间的关系。乳腺癌风险估计值来自于欧洲血统的 122977 例病例（其中 69501 例为雌激素受体（ER）阳性，21468 例为 ER 阴性）和 105974 例对照的公开可用的乳腺癌协会联盟（BCAC）GWAS 汇总统计数据中检索到。进行了随机效应逆方差加权（IVW）MR 分析，并进行了几项敏感性分析，以评估潜在的 MR 假设违反的影响。
女性中每天增加一杯遗传预测的咖啡摄入量与总风险无关（IVW 随机效应；优势比（OR）：0.91，95%置信区间（CI）：0.80-1.02，P：0.12，仪器异质性 P：7.17e-13），ER 阳性（OR=0.90，95%CI：0.79-1.02，P：0.09）和 ER 阴性乳腺癌（OR：0.88，95%CI：0.75-1.03，P：0.12）。在使用 MR-Egger（总乳腺癌；OR：1.00，95%CI：0.80-1.25）、加权中位数（OR：0.97，95%CI：0.89-1.05）和加权模式（OR：1.00，CI：0.93-1.07）的敏感性分析中也发现了无效关联。
这项大型 MR 研究的结果不支持遗传预测的咖啡摄入量与乳腺癌风险之间存在关联，但我们不能排除存在弱关联的可能性。
