Mammographic Density and Candidate Gene Variants: A Twins and Sisters Study
- Jennifer Stone1,
- Lyle C. Gurrin1,
- Graham B. Byrnes1,
- Christopher J. Schroen2,
- Susan A. Treloar3,
- Emma J.D. Padilla4,
- Gillian S. Dite1,
- Melissa C. Southey2,
- Vanessa M. Hayes4,5 and
- John L. Hopper1
- 1Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology and 2Genetic Epidemiology Laboratory, University of Melbourne, Melbourne, Victoria, Australia; 3Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia; and 4Garvan Institute of Medical Research, Cancer Research Program, and 5Department of Medicine, St. Vincent's Hospital Clinical School, University of New South Wales, Sydney, New South Wales, Australia
- Requests for reprints:
John Hopper, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, 2/723 Swanston Street, Carlton, Victoria 3053, Australia. Phone: 61-0383440697; Fax: 61-0393495815. E-mail: j.hopper{at}unimelb.edu.au
Abstract
Background: Mammographic density, the light/white radiographic appearance on a mammogram that represents connective and epithelial tissue, is a strong risk factor for breast cancer which seems to be highly heritable. Little is known about its genetic determinants.
Methods: We studied 457 women from 207 sisterhoods (104 monozygotic twins, 182 dizygotic twins, and 171 singletons). Percentage mammographic density (PMD) as well as dense area and nondense area were calculated using a computer-assisted method. We measured six single nucleotide polymorphisms from six candidate genes (COMT, HSD3B1, IGFBP3, HER2, XPD, and XRCC3). Associations between genotypes and mammographic measures were tested (a) cross-sectionally using a multivariate normal model fitted using FISHER that allowed separate correlations for monozygotic, dizygotic, and nontwin pairs and (b) within sister pairs using paired t tests.
Results: Cross-sectionally, each additional copy of the HSD3B1 Asn367Thr variant allele was associated with lower PMD (−3.47% per allele; SE = 1.65; P = 0.035). Within-pair regression estimates confirmed this association. There was no evidence for an association between the mammographic density measures and any of the other variants studied.
Conclusion: We have replicated an association between a variant in the HSD3B1 gene and PMD, which suggests that HSD3B1 may be genetic determinant of mammographic density. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1479–84)
- mammography density
- genes
- breast cancer
- risk factor
- twins
- epidemiology
- infections and the etiology of cancer
Footnotes
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Grant support: Victorian Breast Cancer Research Consortium, National Health and Medical Research Council, Cancer Institute of New South Wales, and BNP Paribas Foundation. This research is also part of the PhD Candidature of J. Stone funded in part by The Cancer Council Victoria.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted May 10, 2007.
- Received February 4, 2007.
- Revision received April 29, 2007.
