There is insufficient information about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). This study looks for evidence of gene-environment interactions, and compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. They tested gene-environment interactions in 7610 women who developed breast cancer and 10196 controls without the disease, studying the effects of12 polymorphisms FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3Kl-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rsl045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rsI982073, and ATM-rs1800054 in relation to prospectively collected information about ten established environmental risk factors age at menarche, parity, age at first birth, breastfeeding, menopausal status, age t menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption. After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene-environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3Kl-rs889312 were significantly shorter than non-carriers . Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors.
Travis et al 2010 Lancet Gene-environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study vol 375 2143-2151