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...

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