Abstract P2-01-07: Analysis of the relationship between breast cancer risk-related gene polymorphisms, ESR1/6q25.1-rs2046210 and mammographic breast density

Abstract

Abstract Background: Based on the results of a case-control study performed in Japan (Okayama and Kagawa), it was revealed that gene polymorphisms of the estrogen receptor (single nucleotide polymorphisms, SNPs), ESR1/6q25.1-rs2046210 and rs3757318, were closely related to breast cancer risk in Japanese women, and that the odds ratios per allele of individual SNPs were 1.37 [95% CI: 1.1 - 1.7] and 1.33 [1.04 - 1.7], respectively (San Antonio Breast Cancer Symposium 2012, Mizoo et al.). To examine the effects of these SNPs on the pathogenic mechanism of breast cancer, we analyzed the relationship of SNPs with reproductive/physiological factors (age of menarche and number of births), physical factors (height and Body Mass Index [BMI]), family history and mammographic breast density. Methods: Among the patients enrolled in the case-control study, the patients who could be evaluated regarding their lifestyle, SNPs and mammographic breast density were divided into the case group (N = 394) and the control group (N = 511) as the dataset for the study. SNPs were analyzed using the TaqMan genotyping assay® for blood samples. In the analysis of the relationship between SNPs and breast cancer risk, the odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using logistic regression analysis. For the analysis of the relationship between SNPs and the factors, t-test and chi-square test were used. Results: In our dataset, the age-adjusted OR [95% CI] of ESR1/6q25.1-rs2046210 and rs3757318 were 2.22 [1.41 - 3.55] (AA vs. GG) and 2.12 [1.2 - 3.8] (AA vs. GG), respectively, suggesting that they would be significant risk factors. As a result of analyzing the relationship between SNPs and other factors, a significantly lower BMI was observed for the risk allele AA/AG of rs2046210, compared to GG (p = 0.014, t-test). Regarding the mammographic breast density, a significantly higher proportion of mammary glands with high density was confirmed for the risk allele AA/AG of rs2046210, compared to GG (p = 0.0389, chi-square test). The tendency towards a high mammographic breast density in the rs2046210 risk allele AA/AG was also confirmed based upon a stratified analysis of the case and control groups before and after menopause, and a significant correlation was observed, especially before menopause (p = 0.026, chi-square test). Conclusion: Mammographic high breast density is generally considered as one of the breast cancer risks, and it was suggested that gene polymorphisms of ESR1/6q25.1-rs2046210 might affect mammographic breast density. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-01-07.