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

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2007-07, Vol.16 (7), p.1479-1484
• Main Authors: STONE, Jennifer, GURRIN, Lyle C, BYMES, Graham B, SCHROEN, Christopher J, TRELOAR, Susan A, PADILLA, Emma J. D, DITE, Gillian S, SOUTHEY, Melissa C, HAYES, Vanessa M, HOPPER, John L
• Format: Article
• Language: English
• Subjects: 3-Hydroxysteroid Dehydrogenases - genetics; Adult; Aged; Biological and medical sciences; breast cancer; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - genetics; Catechol O-Methyltransferase - genetics; Cohort Studies; Cross-Sectional Studies; DNA-Binding Proteins - genetics; epidemiology; Female; genes; Genetic Variation; Gynecology. Andrology. Obstetrics; Humans; infections and the etiology of cancer; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins - genetics; Mammary gland diseases; Mammography; mammography density; Medical sciences; Middle Aged; Neoplasm Proteins - genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Receptor, ErbB-2 - genetics; risk factor; Siblings; Tropical medicine; Tumors; twins; Twins, Dizygotic - genetics; Twins, Monozygotic - genetics; Xeroderma Pigmentosum Group D Protein - genetics
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-07-0107

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. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1479–84)