Abstract P3-01-08: Mammographic density and estrogen receptor α gene polymorphism in Javanese ethnic women

Abstract

Abstract Background: Mammography density reflects the number of stromal and epithelial and one of strongest risk of BC. Estrogen plays an important role in the occurrence of breast cancer through a mechanism of proliferation and genotoxic effects. Action of estrogen on breast tissue by binding to estrogen receptors. The main estrogen receptor α is coded as ESR1 gene. The most studied variants in this gene are the PvuII and XbaI polymorphisms, which have been associated to lower sensitivity to estrogen. Objective: To determine the proportion of genetic variation ESR1 XbaI and PvuII in Javanese ethnic woman in Yogyakarta, Indonesia and to study the correlation between genetic variations in these genes with mammogram density based on quantitative methods. This reaserch to be used as preventive measures for the development of genetic marker breast cancer risk associated with the density of mammography for younger women who have not entered the age to undergo mammography and can be useful as a reference for evaluation of anti estrogen therapy. Method: Conducted digitizer mammogram density assessment using quantitative rating system based on computer-assisted methods of measurement with cumulus program based on interactive thresholding. Polymorphism identification ESR1 XbaI and PvuII RFLP obtained through PCR process. The numbers of genotyped cases and controls for each marker were 50 cases and 58. Mean of density and frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility. Using anova, independent t-test, cruskal wallis and mann whitney u test we calculated significant different between SNP genotype group. Results: The mean of mammographic density is higher in cases (52%) than in controls (0,41%) (p < 0,05). 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 CT/Pp and TT/pp are 49 % and 48 %, respectively) than in those with the CC/PP genotype (39%), TT VS CC (P >0,05). Women with one or two copies of the XbaI × allele had higher mean percentage density (AG/Xx and AA/xx, 49% and 47%, respectively) than those with the GG/XX genotype (32%,), AAVGG P < 0,05. Persentage of TT genotype and mean of density is higher in cases (30%, 52%) than controls (10,2%, 40%). Conclusion: Haplotype 2 (TG/PX) was associated with lower sensitivity to estrogen and reflects as decrease of mammographic density. The findings of this study support the view that ESR1 polymorphisms may affect breast cancer risk through differences in breast density. Keywords: Breast Cancer, Mammogram Digitizer, DNA polymorphism ESR 1 PvuII, ESR1 XbaI, PCR RFLP Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-08.