Breast cancer risk factors and their effects on survival: a Mendelian randomisation study.
Breast cancer risk factors and their effects on survival: a Mendelian randomisation study.
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乳腺癌危险因素及其对生存率的影响：孟德尔随机化研究
DOI：
10.1186/s12916-020-01797-2
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发表时间：
2020-11-17
期刊：
影响因子：
9.3
通讯作者：
Schmidt MK
中科院分区：
文献类型：
--
作者：
Escala-Garcia M;Morra A;Canisius S;Chang-Claude J;Kar S;Zheng W;Bojesen SE;Easton D;Pharoah PDP;Schmidt MK
观察性研究调查了危险因素与乳腺癌预后的关系。然而，结果存在矛盾，由于潜在的剩余混杂因素，难以确定因果关系。使用孟德尔随机化（MR）方法，我们旨在研究乳腺癌特异性生存率与9个乳腺癌风险因素之间的潜在因果关系：饮酒，体重指数，身高，体力活动，乳腺摄影密度，初潮或绝经年龄，吸烟和2型糖尿病（T2 DM）。我们对来自乳腺癌协会联盟（BCAC）的数据和来自GWAS目录的风险因素汇总估计进行了双样本MR分析。BCAC数据包括86，627名欧洲血统的女性患者，在15年的随访期间有7054例乳腺癌死亡。其中，59，378例为雌激素受体（ER）阳性，13，692例为ER阴性乳腺癌患者。对于显著相关性，我们使用敏感性分析和多变量MR模型。所有危险因素的相关性也在一个模型中进行了检查，该模型由其他预后因素调整。T2 DM遗传易感性增加与乳腺癌特异性生存率降低显著相关（风险比[HR] = 1.10，95%置信区间[CI] = 1.03-1.17，P值[P] = 0.003）。在对ER状态亚型中的任何危险因素进行多重检验校正后，均未发现显著相关性。对于报告的与T2 DM的显著相关性，敏感性分析未显示违反MR假设的证据，也未显示该相关性是由于BMI增加所致。当调整其他预后因素时，这种关联仍然显着。这项广泛的MR分析表明，T2 DM可能与乳腺癌特异性生存率较差存在因果关系，因此治疗T2 DM可能改善预后。
Observational studies have investigated the association of risk factors with breast cancer prognosis. However, the results have been conflicting and it has been challenging to establish causality due to potential residual confounding. Using a Mendelian randomisation (MR) approach, we aimed to examine the potential causal association between breast cancer-specific survival and nine established risk factors for breast cancer: alcohol consumption, body mass index, height, physical activity, mammographic density, age at menarche or menopause, smoking, and type 2 diabetes mellitus (T2DM). We conducted a two-sample MR analysis on data from the Breast Cancer Association Consortium (BCAC) and risk factor summary estimates from the GWAS Catalog. The BCAC data included 86,627 female patients of European ancestry with 7054 breast cancer-specific deaths during 15 years of follow-up. Of these, 59,378 were estrogen receptor (ER)-positive and 13,692 were ER-negative breast cancer patients. For the significant association, we used sensitivity analyses and a multivariable MR model. All risk factor associations were also examined in a model adjusted by other prognostic factors. Increased genetic liability to T2DM was significantly associated with worse breast cancer-specific survival (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.03–1.17, P value [P] = 0.003). There were no significant associations after multiple testing correction for any of the risk factors in the ER-status subtypes. For the reported significant association with T2DM, the sensitivity analyses did not show evidence for violation of the MR assumptions nor that the association was due to increased BMI. The association remained significant when adjusting by other prognostic factors. This extensive MR analysis suggests that T2DM may be causally associated with worse breast cancer-specific survival and therefore that treating T2DM may improve prognosis.
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影响因子：
7.7
作者：
Burgess S
通讯作者：
Burgess S
影响因子：
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作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
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Parkinson, Helen
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Coughlin, SS;Calle, EE;Thun, MJ
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Davies, C.;Godwin, J.;Gray, R.;Clarke, M.;Darby, S.;McGale, P.;Wang, Y. C.;Peto, R.;Pan, H. C.;Cutter, D.;Taylor, C.;Ingle, J.
通讯作者：
Ingle, J.