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Open Access Research article

Sex steroid metabolism polymorphisms and mammographic density in pre- and early perimenopausal women

Carolyn J Crandall1*, Mary E Sehl2, Sybil L Crawford3, Ellen B Gold4, Laurel A Habel5, Lesley M Butler6, MaryFran R Sowers7, Gail A Greendale8 and Janet S Sinsheimer9

Author Affiliations

1 Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, UCLA Medicine/GIM, 911 Broxton Ave., 1st floor, Los Angeles, CA 90024, USA

2 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles 2333 PVUB Los Angeles, CA 90095-7059, USA

3 Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA, 55 Lake Ave. North, Shaw Building, Worcester, MA 01655, USA

4 Department of Public Health Sciences, School of Medicine, University of California, Davis, One Shields Ave., TB 168, Davis, CA 95616, USA

5 Division of Research, Kaiser Permanente, 2000 Broadway, Oakland, CA 94612, USA

6 Department of Public Health Sciences, University of California at Davis, One Shields Ave., 1616 DaVinci Court, Davis, CA 95616, USA

7 Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory, Rm 1846, Ann Arbor, MI 48109-2205, USA

8 Department of Internal Medicine, David Geffen School of Medicine at University of California, Los Angeles, 10945 Le Conte Ave., Ste. 2339, Los Angeles, CA 90095-1687, USA

9 Department of Human Genetics, University of California, Los Angeles, 5-357C Gonda/AV268 CHS, Los Angeles, CA 90095-1766, USA

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Breast Cancer Research 2009, 11:R51  doi:10.1186/bcr2340

Published: 27 July 2009

Abstract

Introduction

We examined the association between mammographic density and single-nucleotide polymorphisms (SNPs) in genes encoding CYP1A1, CYP1B1, aromatase, 17β-HSD, ESR1, and ESR2 in pre- and early perimenopausal white, African-American, Chinese, and Japanese women.

Methods

The Study of Women's Health Across the Nation is a longitudinal community-based cohort study. We analyzed data from 451 pre- and early perimenopausal participants of the ancillary SWAN Mammographic Density study for whom we had complete information regarding mammographic density, genotypes, and covariates. With multivariate linear regression, we examined the relation between percentage mammographic breast density (outcome) and each SNP (primary predictor), adjusting for age, race/ethnicity, parity, cigarette smoking, and body mass index (BMI).

Results

After multivariate adjustment, the CYP1B1 rs162555 CC genotype was associated with a 9.4% higher mammographic density than the TC/TT genotype (P = 0.04). The CYP19A1 rs936306 TT genotype was associated with 6.2% lower mammographic density than the TC/CC genotype (P = 0.02). The positive association between CYP1A1 rs2606345 and mammographic density was significantly stronger among participants with BMI greater than 30 kg/m2 than among those with BMI less than 25 kg/m2 (Pinteraction = 0.05). Among white participants, the ESR1 rs2234693 CC genotype was associated with a 7.0% higher mammographic density than the CT/TT genotype (P = 0.01).

Conclusions

SNPs in certain genes encoding sex steroid metabolism enzymes and ESRs were associated with mammographic density. Because the encoded enzymes and ESR1 are expressed in breast tissue, these SNPs may influence breast cancer risk by altering mammographic density.