Gaudet Mia M, Barrdahl Myrto, Lindström Sara, Travis Ruth C, Auer Paul L, Buring Julie E, Chanock Stephen J, Eliassen A Heather, Gapstur Susan M, Giles Graham G, Gunter Marc, Haiman Christopher, Hunter David J, Joshi Amit D, Kaaks Rudolf, Khaw Kay-Tee, Lee I-Min, Le Marchand Loic, Milne Roger L, Peeters Petra H M, Sund Malin, Tamimi Rulla, Trichopoulou Antonia, Weiderpass Elisabete, Yang Xiaohong R, Prentice Ross L, Feigelson Heather Spencer, Canzian Federico, Kraft Peter
Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Breast Cancer Res Treat. 2016 Feb;155(3):531-40. doi: 10.1007/s10549-016-3681-7. Epub 2016 Jan 23.
Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case-control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values <1.5 × 10(-3) were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43-2.24; P interaction = 1.2 × 10(-4)) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.
目前使用绝经激素治疗（MHT）对绝经后乳腺癌风险具有重要影响，并且观察到的关联可能会受到已知乳腺癌易感基因座的影响。为了最全面地评估前瞻性收集的MHT数据与17个已确认的易感基因座与浸润性乳腺癌风险之间的相互作用，在国立癌症研究所乳腺癌和前列腺癌队列联盟的8个队列中采用了巢式病例对照设计。基于13304例病例和15622例对照的数据，使用多变量调整逻辑回归分析来估计比值比（OR）和95%置信区间（CI）。在乘法尺度上评估当前和过去使用情况的效应修正。P值<1.5×10⁻³被认为具有统计学意义。在9q31-rs865686位点观察到当前MHT效应修正的最强证据。与rs865686 GG基因型的MHT从未使用者相比，当前MHT使用与TT基因型乳腺癌风险之间的关联（OR 1.79，95%CI 1.43-2.24；P相互作用=1.2×10⁻⁴）在乘法尺度上低于预期。MHT与rs865686之间的次乘法相互作用没有生物学意义。绝经激素治疗不太可能与浸润性乳腺癌相关的常见基因变异有强烈相互作用。
