Original Contribution Gene-Environment Interactions for Breast Cancer Risk Among Chinese Women: A Report From the Shanghai Breast Cancer Genetics Study

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 par-ticipants of the Shanghai Breast Cancer Genetics Study (Shanghai, China, 1996–1998 and 2002–2005). Inter-actions 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 in-teraction 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 sig-nificance level (P = 0.037), it did not withstand correction for multiple comparisons. In conclusion, this study re-vealed no apparent interactions between genome-wide association study-identified genetic variants and breast cancer risk factors in the etiology of this common cancer. breast cancer risk; effect measure modification; gene-environment interaction; genetic variants; genome-wid