A functional polymorphism in the promoter of the progesterone receptor gene associated with endometrial cancer risk.

ABSTRACT: Excessive estrogen stimulation unopposed by progesterone strongly predisposes to endometrial cancer. Because the antiproliferative effect of progesterone requires the progesterone receptor (PR), which exists in two isoforms, PR-A and -B, we reasoned that variants in the PR gene may predispose to endometrial cancer. We found six variable sites, including four polymorphisms in the hPR gene and five common haplotypes. One promoter region polymorphism, +331G/A, creates a unique transcription start site. Biochemical assays showed that the +331G/A polymorphism increases transcription of the PR gene, favoring production of hPR-B in an endometrial cancer cell line. Using a case-control study nested within the Nurses' Health Study cohort, we observed a statistically significant association between

SUBMITTER: De Vivo I 

PROVIDER: S-EPMC129433 | biostudies-literature | 2002 Sep

REPOSITORIES: biostudies-literature