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

The major hypothesis proposed to explain endometrial cancer risk is the unopposed estrogen hypothesis which states that elevated levels of plasma estrogens not counterbalanced by high levels of plasma progesterone increase risk of endometrial cancer (1-3). The action of progesterone on the endometrium is mediated by the progesterone receptor (hPR) that exists in two different forms (hPR-A and hPR-B), structurally similar except for their NH2 terminus (164 amino acids longer in hPR-B), which are the result of the transcription from two alternative promoters of the hPR gene and are expressed at approximately the same level in the endometrium. The isoform hPR-B is a transcriptional activator and stimulates epithelial cell growth of endometrium, whereas hPR-A is transcriptionally inactive and inhibits both the estrogen-induced and hPR-B-dependent proliferation of endometrium (4, 5). Recently, in vitro studies by de Vivo et al. (6) showed that a single nucleotide polymorphism, +331G/A (rs10895068) , in the promoter region of the progesterone receptor gene (PGR) increases transcription of the hPR-B form, relative to the hPR-A form. De Vivo et al. also showed a positive association of this polymorphism with the risk of developing endometrial cancer in a case-control study of 187 endometrial cancer cases and 397 matched controls nested within the Nurses’ Health Study cohort (odds ratio, 1.90; 95% confidence interval, 1.10-3.29 for +331A carriers versus noncarriers). Other studies have addressed the relationship of the +331A variant with of cancers of the ovary (7, 8) or breast (9-13) with variable results. With the aim to confirm de Vivo et al.’s findings, we typed the +331G/A polymorphism in a case-control study of 275 endometrial cancer patients and 314 control subjects.