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 van Duijnhoven, F. J.B. Articles by van Gils, C. H. Search for Related Content PubMed PubMed Citation Articles by van Duijnhoven, F. J.B. Articles by van Gils, C. H.

Influence of Estrogen Receptor and Progesterone Receptor Polymorphisms on the Effects of Hormone Therapy on Mammographic Density

¹ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; ² Department of Radiology, Addenbrooke's Hospital, Cambridge Breast Unit; ³ Medical Research Council Dunn Human Nutrition Unit, Cambridge, United Kingdom; and ⁴ Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands

Requests for reprints: Carla H. van Gils, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Mail-drop Str. 6.131, P.O. Box 85500, 3508 GA Utrecht, the Netherlands. Phone: 31-30-2503014; Fax: 31-30-2505485. E-mail: C.vangils{at}umcutrecht.nl

Postmenopausal hormone therapy increases mammographic density, a strong breast cancer risk factor, but effects vary across women. We investigated whether the effect of hormone therapy use is modified by polymorphisms in the estrogen receptor (ESR1) and progesterone receptor (PGR) genes in the Dutch Prospect-EPIC and the English EPIC-Norfolk cohorts. Information on hormone therapy use was obtained through questionnaires at recruitment and after 5 years. Blood samples were collected and consecutive mammograms were available through breast cancer screening programs. For 795 hormone therapy users, one mammogram before and a second mammogram during hormone therapy use was included. For 781 never hormone therapy users, mammograms with similar time intervals were included. Mammographic density was assessed using a computer-assisted method. Changes in density were analyzed using linear regression. A statistically significant difference in percentage density change between hormone therapy users and never users was seen in women with the ESR1 PvuII Pp or pp genotype (2.24%; P < 0.01), but not in those with the PP genotype (0.90%; P = 0.47). Similarly, effects of hormone therapy on percentage density were observed in women with the ESR1 XbaI Xx or xx genotype (2.20%; P < 0.01), but not in those with the XX genotype (–0.65%; P = 0.70). Also, effects were seen in women with the PGR +331 GG genotype (2.04%; P < 0.01), but not in those with the GA or AA genotype (0.98%; P = 0.53). The PGR PROGINS polymorphism did not seem to make women more susceptible to the effects of hormone therapy use. In conclusion, our results suggest that specific polymorphisms in the ESR1 and PGR genes may make women more susceptible to the effects of hormone therapy use on mammographic density. (Cancer Epidemiol Biomarkers Prev 2006;15(3):462–7)

This article has been cited by other articles:

				B. Diergaarde, J. D. Potter, E. R. Jupe, S. Manjeshwar, C. D. Shimasaki, T. W. Pugh, D. C. DeFreese, B. A. Gramling, I. Evans, and E. White Polymorphisms in Genes Involved in Sex Hormone Metabolism, Estrogen Plus Progestin Hormone Therapy Use, and Risk of Postmenopausal Breast Cancer Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1751 - 1759. [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]