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GSTM1, GSTT1, and GSTP1 polymorphisms, breast cancer risk factors and mammographic density in women submitted to breast cancer screening

DOI: 10.1590/S1415-790X2012000200002

Keywords: breast cancer, risk factors, genetic polymorphisms, gstt1, gstm1, gstp1.

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Abstract:

genetic polymorphisms in genes related to the metabolism of xenobiotics, such as genes of the glutathione s-transferases (gstm1, gstt1, and gstp1) superfamily have been associated with an increased risk for breast cancer (bc). considering the high incidence of bc in the city of porto alegre in southern brazil, the purpose of this study was to characterize genotypic and allelic frequencies of polymorphisms in gstm1, gstt1, and gstp1, and correlate these molecular findings with established risk factors for breast cancer including mammographic density, in a sample of 750 asymptomatic women undergoing mammographic screening. molecular tests were performed using the multiplex polymerase chain reaction (pcr) for gstm1 and gstt1, and quantitative pcr for gstp1 polymorphisms. overall, the frequencies of gstm1 and gstt1 null genotypes were 45% and 21%, respectively. for gstp1 polymorphism, genotypic frequencies were 44% for the ile/ile genotype, 44% for the ile/val genotype, and 12% for val/val genotype, with an allelic frequency of 66% for the wild type allele in this population, similar to results of previous international publications. there was a statistically significant association between the combined gstm1 and gstt1 null genotypes (m-/t-) and mammographic density in post menopausal women (p = 0.031). when the gstt1 null (t-) genotype was analyzed isolated, the association with mammographic density in post menopausal women and in the overall sample was also statistically significant (p = 0.023 and p = 0.027, respectively). these findings suggest an association of gstm1 and gstt1 null genotypes with mammographic density.

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