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[Cancer Research 63, 5236-5238, September 1, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

A Functional Polymorphism in the Progesterone Receptor Gene Is Associated with an Increase in Breast Cancer Risk1

Immaculata De Vivo2, Susan E. Hankinson, Graham A. Colditz and David J. Hunter

Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School [I. D., S. E. H., G. A. C., D. J. H.], and Departments of Epidemiology [I. D., S. E. H., G. A. C., D. J. H.], Nutrition [D. J. H.], and Harvard Center for Cancer Prevention [I. D., D. J. H., G. A. C.], Harvard School of Public Health, Boston, Massachusetts 02115

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.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2003 by the American Association for Cancer Research.