No association between the progesterone receptor gene +331G/A polymorphism and breast cancer.

Progesterone is critical to normal breast development, and its activity is mediated by the progesterone receptor (PR) that is part of the steroid-thyroid-retinoic acid receptor superfamily of transcription factors (1). A single copy of the progesterone receptor gene (PGR), located on chromosome 11q22-23, uses separate promoters and translation start sites to produce two protein isoforms, PR-A and PR-B, which are functionally distinct (2). Mouse models have demonstrated that PR-mediated signaling pathways are essential for carcinogen-induced mammary gland carcinogenesis and that mammary gland response to progesterone depends on the ratio of PR-A to PR-B (1). DeVivo et al. (3) resequenced PGR and discovered a single nucleotide polymorphism (+331G/A) that altered transcriptional activity and favored production of PR-B in an endometrial cancer cell line. Further, they showed that this single nucleotide polymorphism was associated with increased risk of both endometrial cancer and breast cancer (3, 4). Given the strong biological evidence that this single nucleotide polymorphism may alter the PR-A to PR-B ratio, we sought to examine the association between PGR +331A/G in a nested case-control study of postmenopausal breast cancer.