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The relationship between estrogen receptor gene polymorphism and mammographic density in postmenopausal women

ABSTRACT Objective To assess the relationship between the presence of PVUII and XBAI polymorphisms in the estrogen receptor α gene and mammographic density in postmenopausal women. Methods For the present analysis, 189 postmenopausal women who had never used hormonal therapy and who did not have clinical or mammographic features were selected. Based on the ACR-BIRADS® 2003 classification, the mammographic density was determined by three independent readers (two subjective ratings and one computerized). Blood samples were available to extract DNA according to KIT GFX® protocol. PCR-RFLP was then used to identify the polymorphisms. Results There was a high degree of agreement among the three readers to determine the mammographic density (κ > 0.75). Sixty women (32%) had dense breasts and 129 (68%) had non-dense breasts. The PVUII polymorphism was found in 132 (69.8%) of 189 women, while the XBAI polymorphism was found in 135 (71.4%) women. Parity (p = 0.02) and body mass index (p < 0.0001) were associated with mammographic density. It was observed that, for the XBAI polymorphism, women with two mutated alleles were approximately 2.5 times more likely to be classified in the dense breasts group (p = 0.003) and the presence of both wild alleles was associated with fibroglandular tissue replacement by fat (p = 0.02). Conclusions There was no significant association of the PVUII polymorphism in the estrogen receptor α gene with mammographic density (p = 0.34). However, the XBAI polymorphism was observed at a higher mutated homozygous frequency in women with dense breasts and there was an increased frequency of wild-type homozygous and heterozygous women with fat-replaced breasts (p = 0.01).