Implications of gene-environment interaction in studies of gene variants in breast cancer: an example of dietary isoflavones and the D356N polymorphism in the sex hormone-binding globulin gene.

TitleImplications of gene-environment interaction in studies of gene variants in breast cancer: an example of dietary isoflavones and the D356N polymorphism in the sex hormone-binding globulin gene.
Publication TypeJournal Article
Year of Publication2006
AuthorsLow, Y-L, Dunning, AM, Dowsett, M, Luben, RN, Khaw, K-T, Wareham, NJ, Bingham, SA
JournalCancer Res
Volume66
Issue18
Pagination8980-3
Date Published2006 Sep 15
ISSN0008-5472
KeywordsAromatase, Breast Neoplasms, Cross-Sectional Studies, Diet, Female, Humans, Isoflavones, Middle Aged, Polymorphism, Genetic, Sex Hormone-Binding Globulin
Abstract

Studies to identify common genetic variants contributing to breast cancer risk often yield inconsistent results. Breast cancer is a complex disease involving both genetic and environmental determinants. Dietary isoflavones are thought to reduce breast cancer risk by stimulating circulating sex hormone-binding globulin (SHBG) levels. The SHBG gene contains a D356N polymorphism and the N variant is associated with reduced SHBG clearance compared with the D variant. In this study, we show a significant gene-environment interaction between SHBG D356N polymorphism and dietary isoflavone exposure on circulating SHBG levels in 1,988 postmenopausal women. SHBG levels were positively associated with isoflavones in women carrying the N variant (etap2 = 1.9%; P = 0.006) but not in women carrying only the D variant (etap2 = 0.0%; P = 0.999; P(interaction) = 0.019). This finding shows that the subtle effects of some genetic variants may be magnified and only become detectable in the presence of certain exposures. This gene-environment interaction might explain heterogeneity in studies associating SHBG gene variants and soy consumption with breast cancer risk in Far East population exposed to high isoflavone levels compared with populations with lower levels.

DOI10.1158/0008-5472.CAN-06-2432
Alternate JournalCancer Res.
Citation Key10.1158/0008-5472.CAN-06-2432
PubMed ID16982738
Grant ListG0401527 / / Medical Research Council / United Kingdom
MC_U106179471 / / Medical Research Council / United Kingdom