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

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.

The influence of glutathion S-transferase P-1 polymorphism A313G rs1695 on the susceptibility to cyclophosphamide hematologic toxicity in Indonesian patients

“…This finding is similar to the Yogyakarta, Indonesian, 10 Khazakstan, 16 Chinese, 7 Taiwanese, 17 Brazilian, 18 and Italian. 19 But in Malay subjects from our http://mji.ui.ac.id data showed a significant deviated from HardyWeinberg equilibrium.…”

Association between GSTP1 Genotypes and Hormone Receptor Phenotype in Invasive Ductal Carcinomas of Breast

“…However, to date the results are still somewhat controversial and may vary from population to population. (Gilbert et al, 1993;Silvestrini et al, 1997;Buser et al, 1997;Helzlsouer et al, 1998;Millikan et al, 2000;Mitrunen et al, 2001;Gudmundsdottir et al, 2001;Huang et al, 2003;Egan et al, 2004;Sreenath et al, 2005;Moureau-Zabotto et al, 2006;Unlu et al, 2008;Saxena et al, 2009;Arun et al, 2010;Pongtheerat et al, 2011;Zhang et al, 2011;Ramalhinho et al, 2011;Aguiar et al, 2012;Ramalhinho et al, 2012;Saxena et al, 2013;Khabaz, 2014;Rodríguez et al, 2014).…”

“…Many studies investigated the possible link between GSTP1 polymorphisms and breast cancer risk, and have shown conflicting results (Gilbert et al, 1993;Silvestrini et al, 1997;Buser et al, 1997;Helzlsouer et al, 1998;Millikan et al, 2000;Mitrunen et al, 2001;Gudmundsdottir et al, 2001;Huang et al, 2003;Egan et al, 2004;Sreenath et al, 2005;Moureau-Zabotto et al, 2006;Unlu et al, 2008;Saxena et al, 2009;Arun et al, 2010;Pongtheerat et al, 2011;Zhang et al, 2011;Ramalhinho et al, 2011;Aguiar et al, 2012;Ramalhinho et al, 2012;Khabaz, 2014;Rodríguez et al, 2014). Many previous studies revealed GSTP1 polymorphism has no correlation with clinical and pathologic tumor characteristics (Buser et al, 1997;Huang et al, 2003) only a few studies showed an inverse correlation with ER (Gilbert et al, 1993;Silvestrini et al, 1997;Moureau-Zabotto et al, 2006).…”

Association of the GSTM1 null polymorphism with breast cancer in a Mexican population

“…This leads to a lack of expression of the GST mu enzymes that results in decreased antioxidant activity in the cell (Duggan et al, 2013), high accumulation of reactive oxygen species (ROS), and consequently higher susceptibility to carcinogenic events due to DNA damage (McLellan et al, 1997;Wang et al, 2010). It has been suggested that the null GSTM1 is associated with an increased risk of developing some types of cancers including BC (McLellan et al, 1997;de Aguiar et al, 2012;Duggan et al, 2013;Possuelo et al, 2013;Wan et al, 2014). Wan et al (2014), in a meta-analysis study, demonstrated an association of the null GSTM1 genotype with BC in a Chinese population.…”