title: A functional polymorphism in the progesterone receptor gene is associated with an increase in breast cancer risk.
abstract: Biological and epidemiological data suggest that progesterone has an important role in mammary tumorigenesis. Because the effects of progesterone require the progesterone receptor (PGR), which exists in two isoforms, PR-A and PR-B, we sought to determine whether the functional polymorphism, +331 G/A, which causes an increase in the expression of the hPR-B isoform, is related to breast cancer risk. Using a nested case-control study design within the Nurses' Health Study cohort, we genotyped 990 cases and 1,364 controls and observed a statistically significant increased risk of breast cancer among carriers of the +331 A allele (odds ratio, 1.33; 95% confidence interval, 1.01-1.74) compared with subjects with the GG genotype. We also observed a potential interaction between genotype and body mass index (BMI) among postmenopausal women, with the highest risk (odds ratio, 2.30; 95% confidence interval, 1.02-5.21) among obese women (BMI >/=30 kg/m(2)) with the GA or AA genotype compared with lean (BMI <25 kg/m(2)) women with the GG genotype. Our findings suggest that the increased production of hPR-B by the +331 G/A polymorphism may predispose women to breast cancer development through increased hPR-B-dependent stimulation of mammary cell growth.
mesh_terms: D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011980:Receptors, Progesterone / Q000235:genetics*
chemical_list: D011980:Receptors, Progesterone