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Gene-environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study breast cancer

Ruth Travis of the Cancer Epidemiology Unit at the University of Oxford and colleagues investigated the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental risk factors for breast cancer (reproductive, behavioural, and anthropometric). The findings are published in the June edition of the Lancet.
To test for evidence of gene—environment interactions, the researchers compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study.
The researchers tested gene—environment interactions in 7,610 women who developed breast cancer and 10,196 controls without the disease, studying the effects of 12 polymorphisms in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at 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 MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162·4 cm [95% CI 162·1—162·7] vs 163·1 cm [162·9—163·2]; p=0·01 after allowance for multiple testing).
The researchers conclude that risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors.
Source: Gene-environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study . Ruth C Travis, Gillian K Reeves, Jane Green, Diana Bull, Sarah J Tipper, Krys Baker, Valerie Beral, Richard Peto, John Bell, Diana Zelenika, Mark Lathrop, for the Million Women Study Collaborators.The Lancet,  Volume 375, Issue 9732, Pages 2143 - 2151, 19 June 2010

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