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. Copyright,
Cancer Epidemiology, Biomarkers & Prevention
Erasmus MC: University Medical Center Rotterdam

van Duijnhoven, F. J., Bezemer, I., Peeters, P., Roest, M., Uitterlinden, A., Grobbee, D., & van Gils, C. (2005). Polymorphisms in the estrogen receptor α gene and mammographic density. Cancer Epidemiology, Biomarkers & Prevention, 14(11 I), 2655–2660. doi:10.1158/1055-9965.EPI-05-0398