Volume 125, Issue 7 pp. 1685-1691
Epidemiology

+331G/A variant in the progesterone receptor gene, postmenopausal hormone use and risk of breast cancer

Joanne Kotsopoulos

Corresponding Author

Joanne Kotsopoulos

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Fax: 617-525-2008.

Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USASearch for more papers by this author
Shelley S. Tworoger

Shelley S. Tworoger

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Department of Epidemiology, Harvard School of Public Health, Boston, MA

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Immaculata DeVivo

Immaculata DeVivo

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Department of Epidemiology, Harvard School of Public Health, Boston, MA

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Susan E. Hankinson

Susan E. Hankinson

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Department of Epidemiology, Harvard School of Public Health, Boston, MA

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David J. Hunter

David J. Hunter

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Department of Epidemiology, Harvard School of Public Health, Boston, MA

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Walter C. Willett

Walter C. Willett

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Department of Epidemiology, Harvard School of Public Health, Boston, MA

Department of Nutrition, Harvard School of Public Health, Boston, MA

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Wendy Y. Chen

Wendy Y. Chen

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

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First published: 06 April 2009
Citations: 11

Abstract

A functional promoter polymorphism in the progesterone receptor (PR) gene previously has been associated with an increased risk of postmenopausal breast cancer. Whether the relationship between genetic variation in PR and risk of breast cancer is modified by postmenopausal hormone (PMH) use is unknown. Thus, we conducted a case–control study nested within the prospective Nurses' Health Study to evaluate if the risk of breast cancer associated with having the +331 A risk allele was modified by PMH use. Genotyping of this SNP was available for 1,664 postmenopausal breast cancer cases and 2,391 controls. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer. Women who were carriers of 1 or both variant A alleles had a 31% increased risk of developing breast cancer (95% CI 1.04–1.65). PMH use significantly modified the association between the +331G/A polymorphism and risk (p-interaction <0.05). Among never users of PMH, women who were variant carriers had a significantly increased risk of breast cancer compared to those with the wild-type genotype (OR = 2.57; 95% CI 1.64–4.02). The +331G/A polymorphism was not associated with breast cancer risk among past (OR = 1.23; 95% CI 0.77–1.97) or current (OR = 1.14; 95% CI 0.84–1.56) PMH users. The data from this large prospective study provide evidence for a 2-fold increased risk of developing postmenopausal breast cancer among never users of PMH with the +331G/A SNP. This finding adds to the evidence that the PR has an important etiologic role in breast cancer and should be evaluated in future studies. © 2009 UICC

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