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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.Abbreviations: CI, confidence interval; GRS, genetic risk score; OR, odds ratio; SNP, single nucleotide polymorphism. [ABSTRACT FROM PUBLISHER]

Etiologic differences between subtypes of breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status are not well understood. The authors evaluated associations of hormone-related factors with breast cancer subtypes in a population-based case-control study involving 1,409 ER-positive (ER+)/PR-positive (PR+) cases, 712 ER-negative (ER−)/PR-negative (PR−) cases, 301 ER+/PR− cases, 254 ER−/PR+ cases, and 3,474 controls aged 20–70 years in Shanghai, China (phase I, 1996–1998; phase II, 2002–2005). Polytomous logistic regression and Wald tests for heterogeneity across subtypes were conducted. Breast cancer risks associated with age at menarche, age at menopause, breastfeeding, age at first livebirth, waist-to-hip ratio, and oral contraceptive use did not differ by hormone receptor status. Among postmenopausal women, higher parity (≥2 children vs. 1) was associated with reduced risk (odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.52, 0.91) and higher body mass index (BMI; weight (kg)/height (m)2) with increased risk (highest quartile: OR = 2.40, 95% CI: 1.65, 3.47) of the ER+/PR+ subtype but was unrelated to the ER−/PR− subtype (for parity, Pheterogeneity = 0.02; for BMI, Pheterogeneity < 0.01). Hormone replacement therapy (OR = 2.25, 95% CI: 1.40, 3.62) and alcohol consumption (OR = 1.59, 95% CI: 1.01, 2.51) appeared to be preferentially associated with the ER+/PR− subtype. These findings indicate that BMI, parity, hormone replacement therapy, and alcohol consumption may play different roles in subtypes of breast cancer. More research is needed to better understand the etiology of 2 relatively rare subtypes, ER+/PR− tumors and ER−/PR+ tumors. [ABSTRACT FROM PUBLISHER]