Influence of GSTT1, GSTM1 and GSTP1 Polymorphisms on the Development of Breast Cancer

Abstract

Introduction: Every year, more than 10 million women are diagnosed worldwide with breast cancer. Breast cancer remains the leading cause of death from malignancy in women. In Mexico about 12 Mexican women die every day from this disease. Glutathione S-transferase (GST) family consists of a group of isoenzymes involved in Phase II detoxification of xenobiotics by glutathione conjugation. There have been reports showing GST polymorphisms as a risk factor for developing cancer. Objective: Determine if the frequencies of polymorphisms of GSTT1, GSTM1 and GSTP1 are associated with breast cancer development. Materials and Methods: We studied 22 women with breast cancer and a control group of 30 women. DNA was extracted from blood. Polymorphisms of T1 and M1 were identified by multiplex PCR. The identification of GSTP1b (exon 5) and GSTP1c (exon 6), was performed separately by RFLP-PCR, using BsmAI and AciI enzymes respectively. Results: Frequencies of polymorphisms were as follows: for breast cancer group 33% null GSTT1 vs 40% null in the control, 32% null GSTM1 vs 63% of control; 63% heterozygote GSTP1b P1a/P1b and 18% homozygote P1b/P1b, vs 53% heterozygote and 20% homozygote in the control, 41% heterozygote P1a/P1c GSTP1c and 0% homozygote vs 10% heterozygote P1c/P1c and 0% homozygote control. Significant differences were found between GSTM1 and GSTP1c polymorphisms with GSTM1 null percentage higher in the control group and a higher frequency of P1c heterozygotes in the cancer group. Conclusion: As this is a pilot study where the results showed no association with breast cancer, further investigation is required on the involvement of GST genes in neoplasm development.

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

“…Similar relation was found in tumors with heterozygote genotype of GSTP1 regarding positive and negative IHC PR stain and tumor grade. These results are consistent with studies that showed an inverse correlation with ER (Gilbert et al, 1993;Silvestrini et al, 1997;MoureauZabotto et al, 2006;Rodríguez et al, 2014), and the two studies of Pongtheerat and colleagues which reported GSTP1 polymorphism was unrelated to increased risk of breast cancer, but found an inverse relationship between GSTP1 genotype and progesterone receptor protein (Pongtheerat et al, 2009;Pongtheerat et al, 2011), and positive correlation with better tumor differentiation and grade (Cairns et al, 1992;Haas et al, 2006). The findings of the current study are in harmony with the report of Ge et al who reported that GSTP1 105Val allele carriers were more liable to have a higher histological grade tumor and negative ER stain than Ile/Ile allele carriers (Ge et al, 2013).…”

“…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).…”

Genetic polymorphisms of glutathione S transferase and cervical intraepithelial neoplasia

“…As only a part of the HPV infected women develop precancerous cervical lesions or cancer, prophylactic evaluation of GST family enzymes could play a major role in identifying high risk individuals for an efficient therapeutic interference, here including HPV vaccination (42,43).…”

Research Article Synergic effect of oral contraceptives, GSTP1 polymorphisms, and high-risk HPV infection in development of cervical lesions.

“…The GSTP1 gene, a member of the GST Pi class, has approximately 3.2 kb and is found on chromosome 11q13 (Rodríguez et al, 2014). GSTP1 is involved in cell protection through the apoptotic process, and its polymorphic forms do not synthesize essential proteins that bind to enzymes present in the JNK pathway (De Luca et al, 2012).…”