Polymorphisms in the Estrogen Receptor α Gene and Mammographic Density
- Fränzel J.B. van Duijnhoven1,
- Irene D. Bezemer1,
- Petra H.M. Peeters1,
- Mark Roest2,
- André G. Uitterlinden3,
- Diederick E. Grobbee1 and
- Carla H. van Gils1
- 1Julius Center for Health Sciences and Primary Care and 2Research Laboratory of the Department of Clinical Chemistry, University Medical Center, Utrecht, the Netherlands; and 3Department 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
Abstract
The presence of the PvuII or the XbaI polymorphism in the estrogen receptor α gene (ESR1, 6q25) has been related to breast cancer risk; however, results are not fully consistent. To further elucidate this relation, we examined these polymorphisms in relation with mammographic density, a measure of dense tissue in the breast, which is strongly associated with breast cancer risk. For this study, 620 participants aged 49 to 68 years were selected from the Prospect-European Prospective Investigation into Cancer and Nutrition cohort. Blood samples, lifestyle– and medical questionnaire data and mammograms were available for these women. Genotyping was done using the TaqMan PCR assay and mammographic density was assessed using a computer-assisted method. Means of mammographic density were compared by ESR1 genotypes and haplotypes. The percentage density was higher in women with one or two copies of the PvuII p allele (means for Pp and pp are 37% and 36%, respectively) than in those with the PP genotype (32%, Ptrend = 0.09). Women with one or two copies of the XbaI x allele had higher mean percentage density (Xx and xx, 36% and 37%, respectively) than those with the XX genotype (31%, Ptrend < 0.01). Haplotype 1 (px) was associated with increased density, whereas haplotype 2 (PX) was associated with decreased density, both suggesting an allele-dose effect (Ptrend = 0.08 and <0.01, respectively). Similar associations were found with absolute density (Ptrend < 0.01). The findings of this study support the view that ESR1 polymorphisms may affect breast cancer risk through differences in breast density.
Footnotes
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Grant support: Dutch Cancer Society grant UU 2002-2716.
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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 September 9, 2005.
- Received June 2, 2005.
- Revision received August 4, 2005.
