Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, 17177, Stockholm, Sweden.
BMC Med. 2020 Dec 2;18(1):370. doi: 10.1186/s12916-020-01839-9.
Observational studies have shown that milk consumption is inversely associated with colorectal, bladder, and breast cancer risk, but positively associated with prostate cancer. However, whether the associations reflect causality remains debatable. We investigated the potential causal associations of milk consumption with the risk of colorectal, bladder, breast, and prostate cancer using a genetic variant near the LCT gene as proxy for milk consumption.
We obtained genetic association estimates for cancer from the UK Biobank (n = 367,643 women and men), FinnGen consortium (n = 135,638 women and men), Breast Cancer Association Consortium (n = 228,951 women), and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254 men). Milk consumption was proxied by a genetic variant (rs4988235 or rs182549) upstream of the gene encoding lactase, which catalyzes the breakdown of lactose.
Genetically proxied milk consumption was associated with a reduced risk of colorectal cancer. The odds ratio (OR) for each additional milk intake increasing allele was 0.95 (95% confidence interval [CI] 0.91-0.99; P = 0.009). There was no overall association of genetically predicted milk consumption with bladder (OR 0.99; 95% CI 0.94-1.05; P = 0.836), breast (OR 1.01; 95% CI 1.00-1.02; P = 0.113), and prostate cancer (OR 1.01; 95% CI 0.99-1.02; P = 0.389), but a positive association with prostate cancer was observed in the FinnGen consortium (OR 1.07; 95% CI 1.01-1.13; P = 0.026).
Our findings strengthen the evidence for a protective role of milk consumption on colorectal cancer risk. There was no or limited evidence that milk consumption affects the risk of bladder, breast, and prostate cancer.
观察性研究表明，牛奶的摄入与结直肠癌、膀胱癌和乳腺癌的风险呈负相关，但与前列腺癌的风险呈正相关。然而，这些关联是否反映了因果关系仍存在争议。我们使用 LCT 基因附近的遗传变异作为牛奶摄入的替代物，研究了牛奶摄入与结直肠癌、膀胱癌、乳腺癌和前列腺癌风险的潜在因果关系。
我们从英国生物银行（n=367643 名女性和男性）、芬兰遗传研究（n=135638 名女性和男性）、乳腺癌协会联盟（n=228951 名女性）和前列腺癌协会基因组协会（n=140254 名男性）获得了癌症的遗传关联估计。牛奶的摄入量由编码乳糖酶的基因上游的一个遗传变异（rs4988235 或 rs182549）来表示，乳糖酶可以分解乳糖。
遗传上预测的牛奶摄入量与结直肠癌风险降低有关。每个增加的牛奶摄入等位基因的比值比（OR）为 0.95（95%置信区间 [CI] 0.91-0.99；P=0.009）。总体而言，遗传预测的牛奶摄入量与膀胱癌（OR 0.99；95%CI 0.94-1.05；P=0.836）、乳腺癌（OR 1.01；95%CI 1.00-1.02；P=0.113）和前列腺癌（OR 1.01；95%CI 0.99-1.02；P=0.389）无关联，但在芬兰遗传研究中观察到与前列腺癌呈正相关（OR 1.07；95%CI 1.01-1.13；P=0.026）。
我们的研究结果加强了牛奶摄入对结直肠癌风险具有保护作用的证据。没有或有限的证据表明牛奶摄入会影响膀胱癌、乳腺癌和前列腺癌的风险。
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