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/m2) with the GA or AA genotype compared with lean (BMI <25 kg/m2) 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.
|Number of pages||3|
|State||Published - Sep 1 2003|