Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Am J Epidemiol. 2013 Jan 15;177(2):161-70. doi: 10.1093/aje/kws238. Epub 2012 Dec 6.
Genome-wide association studies have identified approximately 20 susceptibility loci for breast cancer. A cumulative genetic risk score (GRS) was constructed from 10 variants with replicated associations among participants of the Shanghai Breast Cancer Genetics Study (Shanghai, China, 1996-1998 and 2002-2005). Interactions between the GRS and 11 breast cancer risk factors were evaluated. Among the 6,408 study participants, no evidence of effect modification was found with the GRS for age at menarche, age at menopause, age at first live birth/parity, total months of breastfeeding, family history of breast cancer, history of benign breast disease, hormone replacement therapy, body mass index, waist/hip ratio, or regular physical activity. The effect of the GRS was least homogeneous by duration of menstruation; further analysis indicated a nominally significant interaction with one genetic variant. The mitochondrial ribosomal protein S30 gene (MRPS30) rs10941679 was associated with breast cancer risk only among women with more than 30 years of menstruation (odds ratio = 1.15, 95% confidence interval: 1.05, 1.26). Although this multiplicative interaction reached a nominal significance level (P = 0.037), it did not withstand correction for multiple comparisons. In conclusion, this study revealed no apparent interactions between genome-wide association study-identified genetic variants and breast cancer risk factors in the etiology of this common cancer.
全基因组关联研究已经确定了大约 20 个乳腺癌易感性位点。一个累积的遗传风险评分(GRS)是由 10 个在上海乳腺癌遗传学研究(中国上海,1996-1998 年和 2002-2005 年)参与者中具有复制关联的变体构建的。评估了 GRS 与 11 个乳腺癌危险因素之间的相互作用。在 6408 名研究参与者中,GRS 与初潮年龄、绝经年龄、首次活产/生育年龄、总母乳喂养月数、乳腺癌家族史、良性乳腺疾病史、激素替代疗法、体重指数、腰臀比或规律体育活动之间没有发现明显的修饰作用。GRS 的作用在月经持续时间上最不均匀;进一步分析表明,与一个遗传变异有名义上显著的相互作用。线粒体核糖体蛋白 S30 基因(MRPS30)rs10941679 仅与月经超过 30 年的女性的乳腺癌风险相关(比值比=1.15,95%置信区间:1.05,1.26)。尽管这种乘法相互作用达到了名义显著性水平(P=0.037),但它没有经受住多次比较的校正。总之,这项研究表明,在这种常见癌症的病因学中,全基因组关联研究确定的遗传变异与乳腺癌危险因素之间没有明显的相互作用。