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. 2007 Jul;16(7):1479-84.
doi: 10.1158/1055-9965.EPI-07-0107.

Mammographic Density and Candidate Gene Variants: A Twins and Sisters Study

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Mammographic Density and Candidate Gene Variants: A Twins and Sisters Study

Jennifer Stone et al. Cancer Epidemiol Biomarkers Prev. .
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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 Asn(367)Thr 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.

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