This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Warren, R. Articles by Easton, D. Search for Related Content PubMed PubMed Citation Articles by Warren, R. Articles by Easton, D.

Associations among Mammographic Density, Circulating Sex Hormones, and Polymorphisms in Sex Hormone Metabolism Genes in Postmenopausal Women

¹ Department of Radiology, University of Cambridge, Addenbrooke's Hospital; ² Cancer Research UK, Department of Oncology, University of Cambridge; ³ European Prospective Investigation into Cancer and Nutrition and ⁴ Cancer Research UK, Genetic Epidemiology Group, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom; ⁵ Population Health Group, School of Medicine, Health Policy and Practice, University of East Anglia; ⁶ Department of Radiology, Norfolk and Norwich Hospital, Norwich, United Kingdom; and ⁷ Academic Department of Biochemistry, Royal Marsden Hospital, London, United Kingdom

Requests for reprints: Ruth Warren, Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom. Phone: 44-1223-586959; Fax: 44-1223-217886. E-mail: rmlw2{at}cam.ac.uk

Mammographic density and serum sex hormone levels are important risk factors for breast cancer, but their associations with one another are unclear. We studied these phenotypes, together with single nucleotide polymorphisms (SNP) in genes related to sex hormone metabolism, in a cross-sectional study of 1,413 postmenopausal women from the European Prospective Investigation into Cancer and Nutrition-Norfolk. All women were >1 year postmenopausal and had not taken hormone replacement therapy for >3 months before sampling. Serum levels of 7 sex hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG), androstenedione, 17-OH-progesterone, estrone, and estrone sulfate] and 15 SNPs in the CYP17, CYP19, EDH17B2, SHBG, COMT, and CYP1B1 genes were studied. Mammograms nearest in time to the blood sampling were identified through the national breast screening program and visually assessed by three radiologists using the Boyd six-category and Wolfe four-category scales. We found a weak positive association between mammographic density and SHBG levels (P = 0.09) but no association with any other hormones. None of the SNPs, including those shown previously to be associated with estradiol or SHBG, showed significant associations with density. We conclude that mammographic density is largely independent of postmenopausal steroid hormone levels, indicating that these risk factors have, to a large extent, an independent etiology and suggesting that they may be independent predictors of breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1502-08)

This article has been cited by other articles:

				L. E. Kelemen, V. S. Pankratz, T. A. Sellers, K. R. Brandt, A. Wang, C. Janney, Z. S. Fredericksen, J. R. Cerhan, and C. M. Vachon Age-specific Trends in Mammographic Density: The Minnesota Breast Cancer Family Study Am. J. Epidemiol., May 1, 2008; 167(9): 1027 - 1036. [Abstract] [Full Text] [PDF]

				T. M. Peters, U. Ekelund, M. Leitzmann, D. Easton, R. Warren, R. Luben, S. Bingham, K.-T. Khaw, and N. J. Wareham Physical Activity and Mammographic Breast Density in the EPIC-Norfolk Cohort Study Am. J. Epidemiol., March 1, 2008; 167(5): 579 - 585. [Abstract] [Full Text] [PDF]

				C. Nagata, T. Matsubara, T. Hara, H. Fujita, Y. Nagao, S. Yamamoto, C. Shibuya, Y. Kashiki, and H. Shimizu Urinary 6-Sulfatoxymelatonin and Mammographic Density in Japanese Women Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2509 - 2512. [Abstract] [Full Text] [PDF]

				C. M. Vachon, T. A. Sellers, E. E. Carlson, J. M. Cunningham, C. A. Hilker, R. L. Smalley, D. J. Schaid, L. E. Kelemen, F. J. Couch, and V. S. Pankratz Strong Evidence of a Genetic Determinant for Mammographic Density, a Major Risk Factor for Breast Cancer Cancer Res., September 1, 2007; 67(17): 8412 - 8418. [Abstract] [Full Text] [PDF]