Abstract
The enzymes encoded by glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism of wide range of carcinogens that are ubiquitous in the environment. Homozygous deletions of the GSTM1 and GSTT1 genes are commonly found and result in lack of enzyme activity. This study was undertaken to evaluate the association between GSTM1, GSTT1 and GSTP1 gene polymorphism and breast cancer risk in Mizoram population. Odd ratio (OR) and 95% confidence interval (CI) from conditional logistic regression model were used to estimate the association between genetic polymorphism and breast cancer risk. The GSTM1 and GSTT1 null genotypes were associated with an increased risk of breast cancer [OR = 10.80 (95% CI 1.16–100.43)]. The risk of breast cancer associated with the GSTT1 null genotype was observed to be low among postmenopausal women. When considered together, GSTM1 and GSTT1 genotypes were found to be associated with an increased risk of breast cancer. The relationship between GSTM1 and GSTT1 gene deletions and breast cancer risk was substantially altered by consumption of Smoked Meat/Vegetable. In the present study, GSTP1Ile105Val (rs1695) polymorphism was related to breast cancer susceptibility or phenotype. Our data provides evidence for substantially increased risk of breast cancer associated with GSTM1 and/or GSTT1 homozygous gene deletions in Mizoram population.
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References
Agudo A, Sala N, Pera G et al (2006) Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 15:2427–2434
Ali-Osman F, Akande O, Antoun G, Mao JX, Buolamwini J (1997) Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem 272:10004–10012
Arand M, Mühlbauer R, HenGSTler J, Jäger E, Fuchs J, Winkler L, Oesch F (1996) A multiplex polymerase chain reaction protocol for the simultaneous analysis of the glutathione S-transferase GSTM1 and GSTT1 polymorphisms. Anal Biochem 236:184–186
Buchard A, Sanchez JJ, Dalhoff K, Morling N (2007) Multiplex PCR detection of GSTM1, GSTT1, and GSTP1 gene variants. J Mol Diagn 9(5):612–617
García-Closas M, Kelsey TK, Hankinson ES (1999) Glutathione S-transferase Mu and Theta polymorphisms and breast cancer susceptibility. J Natl Cancer Inst 91:1960–1964
Ghatak S, Muthukumaran RB, Nachimuthu SK (2013) A simple method of genomic DNA extraction from human samples for PCR-RFLP analysis. J Biomol Tech 24(4):224–231
Ghatak S, Doris L, Mawia L, Ricky S, Zothanpuia Jeremy LP, Muthukumaran RB, Senthil-Kumar N (2014) Mitochondrial D-Loop and cytochrome oxidase subunit I polymorphisms among the breast cancer patients of Mizoram, Northeast India. Curr Genet 60:201–212
Lizard-Nacol S, Coudert B, Colosetti P, Riedinger JM et al (1999) Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer. Breast Cancer Res 1:81–87
Murthy NS, Chaudhry K, Nadayil D, Agarwal UK, Saxena S (2009) Changing trends in incidence of breast cancer: Indian scenario. Indian J Cancer 46:73–74
National Cancer Registry Programme (NCRP) (2013) Three year report of the population based cancer registries 2009–2011. (Report of 25 PBCRs in India), Bangalore. Indian Council Med Res 25:1–16
Samson M, Swaminathan R, Rama R et al (2007) Role of GSTM1 (Null/Present), GSTP1 (Ile105Val) and P53 (Arg72Pro) genetic polymorphisms and the risk of breast cancer: a case control study from South India. Asian Pac J Cancer 8:253–257
Sieri S, Krogh V, Ferrari P et al (2008) Dietary fat and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 88(5):1304–1312
Unlü A, Ates NA, Tamer L et al (2008) Relation of glutathione S-transferase T1, M1 and P1 genotypes and breast cancer risk. Cell Biochem Funct 26:643–647
Zimniak P, Nanduri B, Pilula S, Bandorowiczpikula J (1994) Naturally occurring human glutathione S-transferase GSTP1.1 isoforms with isoleucine and valine at position 104 differ in enzymatic properties. Eur J Biochem 224:893–899
Acknowledgments
The authors are thankful to the sample donors and the Department of Biotechnology, New Delhi, Govt. of India for financial assistance in the form of State Biotech Hub (BT/04/NE/2009 dt. 29.08.2014) and Bioinformatics Infrastructural Facility [No. BT/BI/12/060/2012 (NERBIF-MUA)].
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Kimi, L., Ghatak, S., Yadav, R.P. et al. Relevance of GSTM1, GSTT1 and GSTP1 Gene Polymorphism to Breast Cancer Susceptibility in Mizoram Population, Northeast India. Biochem Genet 54, 41–49 (2016). https://doi.org/10.1007/s10528-015-9698-5
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DOI: https://doi.org/10.1007/s10528-015-9698-5