No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a multi-center cohort study |
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| Authors: | Rebbeck Timothy R,Antoniou Antonis C,Llopis Trinidad Caldes,Nevanlinna Heli,Aittomäki Kristiina,Simard Jacques,Spurdle Amanda B KConFab,Couch Fergus J,Pereira Lutecia H Mateus,Greene Mark H,Andrulis Irene L Ontario Cancer Genetics Network,Pasche Boris,Kaklamani Virginia Breast Cancer Family Registry,Hamann Ute,Szabo Csilla,Peock Susan,Cook Margaret,Harrington Patricia A,Donaldson Alan,Male Allison M,Gardiner Carol Anne,Gregory Helen,Side Lucy E,Robinson Anne C,Emmerson Louise,Ellis Ian EMBRACE,Peyrat Jean-Philippe,Fournier Joëlle,Vennin Philippe,Adenis Claude,Muller Danièle |
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| Affiliation: | Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. rebbeck@mail.med.upenn.edu |
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| Abstract: | Background The transforming growth factor β-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-β, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92–1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81–1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers. |
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| Keywords: | BRCA1 BRCA2 Risk modifiers Hereditary cancer |
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