Null Results in Brief Transforming Growth Factor B Receptor Type I and Transforming Growth Factor B1 Polymorphisms Are Not Associated with Postmenopausal Breast Cancer

A polymorphic allele in transforming growth factor h receptor 1 (TGFbR1) is hypothesized to increase risk of cancer (1). The allele, designated as TGFbR1*6A , results from the deletion of three alanines within a nine-alanine stretch in exon 1, and in vitro studies have shown that TGFbR1*6A is an impaired mediator of TGF-h antiproliferative signals compared with wild-type (TGFbR1*9A ; refs. 2, 3). Most previous studies (2, 4, 5), including a meta-analysis (6), have found an association between TGFbR1*6A and increased risk of breast cancer, but the majority of these studies were hospital based (2, 5, 6). One study (5) further suggested that TGFbR1*6A interacts with the TGFb1 T29C polymorphism. The TGFb1 29C allele leads to significantly higher serum levels of TGF-h1 (7, 8), is hypothesized to reduce breast cancer risk (8), and has been examined in many previous breast cancer studies (5, 8-15). We used a nested case-control study within the Cancer Prevention Study II Nutrition Cohort (16) to examine whether the TGFbR1*6A allele influenced risk of postmenopausal breast cancer either alone or in combination with TGFb1 T29C .