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Association of GSTM3 intron 6 variant with cigarette smoking, tobacco chewing and alcohol as modifier factors for prostate cancer risk

  • Genotoxicity and Carcinogenicity
  • Published:
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Abstract

Variations in glutathione-S-transferases (GSTs) genes may alter the catalytic efficiency of GST isoenzymes leading to potential increase in susceptibility to carcinogens present in cigarette smoke and tobacco. The present study aimed to explore the association of GSTM3 intron 6 polymorphism with susceptibility to prostate cancer (PCa), and to assess risks associated with cigarette smoking, tobacco chewing and alcohol consumption in PCa patients of North India. The study included 135 PCa patients and 169 controls. All subjects were genotyped for 3-bp deletion in intron 6 of GSTM3. Risk of developing prostate cancer associated with GSTM3 AB + BB was 2.5-fold (OR = 2.51, P = 0.028) as compared to AA genotype. Patients who were either smokers and/or had alcohol habits demonstrated a strong association with GSTM3 (AB + BB) genotype (OR = 4.11, P = 0.046; OR = 4.38, P = 0.027, respectively). Our results suggested GSTM3 (AB + BB) genotype to be significantly associated with PCa risk. The risk was even more apparent in case of cigarette smokers and alcohol consumers.

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References

  • Andersson SO, Baron J, Bergström R, Lindgren C, Wolk A, Adami HO (1996) Lifestyle factors and prostate cancer risk: a case–control study in Sweden. Cancer Epidemiol Biomarkers Prev 5:509–513

    PubMed  CAS  Google Scholar 

  • Brooks JD, Weinstein M, Lin X, Sun Y, Pin SS, Bova GS et al (1998) CG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev 7:531–536

    PubMed  CAS  Google Scholar 

  • Buch SC, Notani PN, Bhisey RA (2002) Polymorphism at GSTM1, GSTM3 and GSTT1 gene loci and susceptibility to oral cancer in an Indian population. Carcinogenesis 23:803–807

    Article  PubMed  CAS  Google Scholar 

  • Gleason DF, Mellinger GT (1974) Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 111:58–64

    PubMed  CAS  Google Scholar 

  • Hayes RB (2001) Gene–environment interrelations in prostate cancer. Epidemiol Rev 23:163–167

    PubMed  CAS  Google Scholar 

  • Hayes JD, Pulford DJ (1995) The glutathione S-transferases supergene family: regulation of GST and contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30:445–600

    Article  PubMed  CAS  Google Scholar 

  • Hayes RB, Brown LM, Schoenberg JB, Greenberg RS, Silverman DT, Schwartz AG et al (1996) Alcohol use and prostate cancer risk in US blacks and whites. Am J Epidemiol 143:692–697

    PubMed  CAS  Google Scholar 

  • Inskip A, Elexperu-Camiruaga J, Buxton N, Dias PS, MacIntosh J, Campbell D et al (1995) Identification of polymorphism at the glutathione S-transferase, GSTM3 locus: evidence for linkage with GSTM1*A. Biochem J 312:713–716

    PubMed  CAS  Google Scholar 

  • Jourenkova-Mironova N, Voho A, Bouchardy C, Wikman H, Dayer P, Benhamou S et al (1999a) Glutathione S-transferase GSTM3 and GSTP1 genotypes and larynx cancer risk. Cancer Epidemiol Biomarkers Prev 8:185–188

    PubMed  CAS  Google Scholar 

  • Jourenkova-Mironova N, Voho A, Bouchardy C, Wikman H, Dayer P, Benhamou S et al (1999b) Glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes and the risk of smoking-related oral and pharyngeal cancers. Int J Cancer 81:44–48

    Article  PubMed  CAS  Google Scholar 

  • Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M et al (2000) Environmental and heritable factors in the causation of cancer. N Engl J Med 343:78–85

    Article  PubMed  CAS  Google Scholar 

  • Loktionov A, Watson MA, Gunter M, Stebbings WS, Speakman CT, Bingham SA et al (2001) Glutathione-S-transferase gene polymorphisms in colorectal cancer patients: interaction between GSTM1 and GSTM3 allele variants as a risk-modulating factor. Carcinogenesis 22:1053–1060

    Article  PubMed  CAS  Google Scholar 

  • Medeiros R, Vasconcelos A, Costa S, Pinto D, Ferreira P, Lobo F et al (2004) Metabolic susceptibility genes and prostate cancer risk in a southern European population: the role of glutathione S-transferases GSTM1, GSTM3, and GSTT1 genetic polymorphisms. Prostate 58:414–420

    Article  PubMed  CAS  Google Scholar 

  • Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  PubMed  CAS  Google Scholar 

  • Mishra D, Thangaraj K, Mandhani A, Kumar A, Mittal R (2005) Is reduced CAG repeat length in androgen receptor gene associated with risk of prostate cancer in Indian population? Clin Genet 68:55–60

    Article  PubMed  Google Scholar 

  • Mitrunen K, Jourenkova N, Kataja V, Eskelinen M, Kosma VM, Benhamou S et al (2001) Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. Cancer Epidemiol Biomarkers Prev 10:229–236

    PubMed  CAS  Google Scholar 

  • Nakajima T, Elovaara E, Anttila S, Hirvonen A, Camus AM, Hayes JD et al (1995) Expression and polymorphism of glutathione S-transferase in human lungs: risk factors in smoking-related lung cancer. Carcinogenesis 16:707–711

    Article  PubMed  CAS  Google Scholar 

  • Pandey SN, Jain M, Nigam P, Choudhuri G, Mittal B (2006) Genetic polymorphisms in GSM1, GSTT1, GSTP1, GSTM3 and susceptibility to gallbladder cancer in North India. Biomarkers 11:250–261

    Article  PubMed  CAS  Google Scholar 

  • Park LY, Muscat JE, Kaur T, Schantz SP, Stern JC, Richie JP Jr et al (2000) Comparison of GSTM polymorphisms and risk for oral cancer between African-Americans and Caucasians. Pharmacogenetics 10:123–131

    Article  PubMed  CAS  Google Scholar 

  • Platz EA, Leitzmann MF, Rimm EB, Willett WC, Giovannucci E (2004) Alcohol intake, drinking patterns, and risk of prostate cancer in a large prospective cohort study. Am J Epidemiol 159:444–453

    Article  PubMed  Google Scholar 

  • Rebbeck TR (1997) Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 6:733–743

    PubMed  CAS  Google Scholar 

  • Schnakenberg E, Breuer R, Werdin R, Dreikorn K, Schloot W (2000) Susceptibility genes: GSTM1 and GSTM3 as genetic riskfactors in bladder cancer. Cytogenet Cell Genet 91:234–238

    Article  PubMed  CAS  Google Scholar 

  • Shi Y, Lee JS, Galvin KM (1997) Everything you have ever wanted to know about Yin Yang 1. Biochim Biophys Acta 1332:F49–F66

    PubMed  CAS  Google Scholar 

  • Sikdar N, Paul RR, Roy B (2004) Glutathione S-transferase M3 (A/A) genotype as a risk factor for oral cancer and leukoplakia among Indian tobacco smokers. Int J Cancer 109:95–101

    Article  PubMed  CAS  Google Scholar 

  • Sinha R, Anderson DE, McDonald SS, Greenwald P (2003) Cancer risk and diet in India. J Postgrad Med 49:222–228

    PubMed  CAS  Google Scholar 

  • Srivastava DSL, Mandhani A, Mittal B, Mittal RD (2005) Genetic polymorphism of glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and susceptibility to prostate cancer in Northern India. BJU Int 95:170–173

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The work was supported by grant from Department of Science and Technology, New Delhi. RS is thankful to Council of Scientific and Industrial Research, New Delhi, for fellowship. We are thankful to Dr. Anil Mandhani for providing samples of patients with prostate cancer and for critical suggestions.

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Correspondence to Rama Devi Mittal.

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Kesarwani, P., Singh, R. & Mittal, R.D. Association of GSTM3 intron 6 variant with cigarette smoking, tobacco chewing and alcohol as modifier factors for prostate cancer risk. Arch Toxicol 83, 351–356 (2009). https://doi.org/10.1007/s00204-008-0343-5

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  • DOI: https://doi.org/10.1007/s00204-008-0343-5

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