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Updated: Aug 31, 2026

An Ex vivo Model to Study Hormone Action in the Human Breast
Published on: January 8, 2015
A functional polymorphism in the progesterone receptor gene is associated with an increase in breast cancer risk
Immaculata De Vivo1, Susan E Hankinson, Graham A Colditz
1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. devivo@channing.harvard.edu
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.
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