Advertisement

Association of GSTM1, GSTT1, and GSTM3 gene polymorphisms and susceptibility to cervical cancer in a North Indian population

Published:January 21, 2008DOI:https://doi.org/10.1016/j.ajog.2007.09.046

      Objective

      The objective of the study was to evaluate the influence of genetic polymorphisms of GSTM1, GSTT1, and GSTM3 on the susceptibility of cervical cancer.

      Study Design

      Blood samples from 150 women with biopsy-confirmed cervical cancer and 168 healthy controls were analyzed by multiplex polymerase chain reaction (PCR) to detect the presence or absence of GSTM1 and GSTT1. Insertion/deletion polymorphism in intron 6 of GSTM3 was determined by PCR.

      Results

      The frequencies of homozygous GSTM1 null and GSTT1 null genotypes were found to be significantly higher in cancer patients as compared with healthy controls (P = .009, odds ratio [OR] 1.52, 95% confidence interval [CI], 1.1 to 2.0 and P = .0004, OR 2.4, 95% CI: 1.4 to 4.0, respectively). The AB genotype of GSTM3 also conferred higher risk of cancer (P = .053, OR 1.64, 95% CI, 1.0 to 2.6). However, no significant association of at-risk genotypes was observed with any stages of cervical cancer. Interactions among GSTM1 null, GSTT1 null, and AB genotype of GSTM3 resulted in additive predictive risks of cervical cancer. In case-only analysis, carriers of the AA genotype of GSTM3 among tobacco users were at elevated risk of cervical cancer (P = .024, OR 2.1, 95% CI, 1.0 to 4.1) as compared with AB and BB genotypes.

      Conclusion

      GSTM1 null, GSTT1 null, and GSTM3*AB genotypes may confer higher susceptibility to cervical cancer and cancer risk because at-risk genotypes are additive. Tobacco usage by carriers of GSTM3*AA has enhanced the risk of cervical cancer as compared with nonusers.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Parkin M.D.
        • Freddie B.
        • Jacques F.
        • Pisani P.
        Estimating the world cancer burden: Globocan 2000.
        Int J Cancer. 2001; 94: 153-156
        • Lee T.S.
        • Kim J.W.
        • Kang G.H.
        • et al.
        DNA hypomethylation of CAGE promotors in squamous cell carcinoma of uterine cervix.
        Ann N Y Acad Sci. 2006; 1091: 218-224
        • Schiffman M.H.
        • Bauer H.M.
        • Hoover R.N.
        • et al.
        Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia.
        J Natl Cancer Inst. 1993; 85: 958-964
        • Winkelstein W.
        Smoking and cervical cancer-current status: a review.
        Am J Epidemiol. 1990; l31: 945-958
        • Pemble S.E.
        • Wardle A.F.
        • Taylor J.B.
        Glutathione S-transferase class kappa: characterization by the cloning of rat mitochondrial GST and identification of a human homologue.
        Biochem J. 1996; 319: 749-754
        • Simons A.M.
        • Mugica van Herckenrode C.
        • Rodriguez J.A.
        • et al.
        Demonstration of smoking-related DNA damage in cervical epithelium and correlation with human papillomavirus type 16, using exfoliated cervical cells.
        Br J Cancer. 1995; 71: 246-249
        • Duell E.J.
        • Holly E.A.
        • Bracci P.M.
        • Liu M.
        • Wiencke J.K.
        • Kelsey K.T.
        A population based case control study of polymorphism in carcinogen metabolizing genes smoking and pancreatic adenocarcinoma risk.
        J Natl Cancer Inst. 2002; 94: 297-306
        • Goodman M.T.
        • McDuffie K.
        • Hernandez B.
        • et al.
        CYP1A1, GSTM1, and GSTT1 polymorphisms and the risk of cervical squamous intraepithelial lesions in a multiethnic population.
        Gynecol Oncol. 2001; 81: 263-269
        • Yengi L.
        • Inskip A.
        • Gilford J.
        • et al.
        Polymorphism at the glutathione S-transferase locus GSTM3: interactions with cytochrome P450 and glutathione S-transferase genotypes as risk factors for multiple cutaneous basal cell carcinoma.
        Cancer Res. 1996; 56: 1974-1977
        • Mitrunen K.
        • Jourenkova N.
        • Kataja V.
        • et al.
        Glutathione S-Transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer.
        Cancer Epidemiol Biomarkers Prev. 2001; 10: 229-236
        • Inskip A.
        • Elexperu-Camiruaga J.
        • Buxton N.
        • et al.
        Identification of polymorphism at the glutathione S-transferase, GSTM3 locus: evidence for linkage with GSTM1*A.
        Biochem J. 1995; 312: 713-716
        • Jourenkova N.
        • Reinikainen M.
        • Bouchardy C.
        • Dayer P.
        • Benhamou S.
        • Hirvonen A.
        Larynx cancer risk in relation to glutathione S-transferase M1 and T1 genotypes and tobacco smoking.
        Cancer Epidemiol Biomarkers Prev. 1998; 7: 19-23
        • Jain M.
        • Kumar S.
        • Lal P.
        • Tiwari A.
        • Ghoshal U.C.
        • Mittal B.
        Role of GSTM3 polymorphism in the risk of developing esophageal cancer.
        Cancer Epidemiol Biomarkers Prev. 2007; 16: 178-181
        • Shiy Y.
        • Lee J.S.
        • Galvin K.M.
        Everything you have ever wanted to know about ying yang I.
        Biochim Biophys Acta. 1997; 1332: 49-66
        • Pandey S.N.
        • Jain M.
        • Nigam P.
        • Choudhari G.
        • Mittal B.
        Genetic polymorphisms in GSTM1, GSTT1, GSTP1, GSTM3 and susceptibility to gallbladder.
        Cancer Biomark. 2006; 11: 250-261
        • Sharma A.
        • Sharma J.K.
        • Murthy N.S.
        • Mitra A.B.
        Polymorphisms at GSTM1 and GSTT1 gene loci and susceptibility to cervical cancer in Indian population.
        Neoplasma. 2004; 51: 12-16
        • Jhavar S.G.
        • Sarin R.
        • Chopra S.
        • et al.
        Females with paired occurrence of cancers in the UADT and genital region have a higher frequency of either glutathione S-transferase M1/T1 null genotype.
        J Carcinog. 2005; 4: 6
        • Joseph T.
        • Chacko P.
        • Wesley R.
        • Jayaprakash P.G.
        • James V.F.
        • Pillai M.R.
        Germline genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes in Indian cervical cancer: associations with tumor progression, age and human papillomavirus infection.
        Gynecol Oncol. 2006; 101: 411-417
        • Miller S.A.
        • Dykes D.D.
        • Polesky H.F.
        A salting procedure for extracting DNA from nucleated cells.
        Nucleic Acid Res. 1988; 16: 1215
        • Setiawan V.W.
        • Zhang Z.F.
        • Yu G.P.
        • et al.
        GSTT1 and GST M1 null genotypes and risk of gastric cancer: a case control study in Chinese population.
        Cancer Epidemol Biomarkers Prev. 2000; 9: 73-80
        • Idle J.R.
        Is environmental carcinogenesis is modulated by host polymorphism?.
        Mutat Res. 1991; 247: 259-266
        • Nebert D.W.
        Role of genetics and drug metabolism in human cancer risk.
        Mutat Res. 1991; 247: 267-281
        • Berhane K.
        • Widersten M.
        • Engstrom A.
        • Kozarich J.W.
        • Mannervik B.
        Detoxication of base propenals and other alpha, beta-unsaturated aldehyde products of radical reactions and lipid peroxidation by human glutathione transferases.
        Proc Natl Acad Sci USA. 1994; 91: 1480-1484
        • Nakachi K.
        • Imai K.
        • Hayashi S.I.
        • Kawajiri K.
        Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population.
        Cancer Res. 1993; 53: 2994-2999
        • Zhong S.
        • Howie A.F.
        • Ketterer B.
        • et al.
        Glutathione S-transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility.
        Carcinogenesis. 1991; 12: 1533-1537
        • Brockmoller J.
        • Kerb R.
        • Drakoulis N.
        • Staffeldt B.
        • Roots I.
        Glutathione S-transferase M1 and its variants A and B as host factors of bladder cancer susceptibility: a case control study.
        Cancer Res. 1994; 54: 4103-4111
        • Cotton S.C.
        • Sharp L.
        • Little J.
        • Brockton N.
        Glutathione S-transferase polymorphisms and colorectal cancer.
        Am J Epidemiol. 2000; 151: 7-32
        • Rebbeck T.R.
        Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility.
        Cancer Epidemiol Biomarkers Prev. 1997; 6: 733-743
        • Buch S.C.
        • Notani P.N.
        • Bhisey R.A.
        Polymorphism at GSTM1, GSTM3 and GSTT1 gene loci and susceptibility to oral cancer in an Indian population.
        Carcinogenesis. 2002; 23: 803-807
        • Jourenkova-Mironova N.
        • Voho A.
        • Bouchardy C.
        • et al.
        Glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes and the risk of smoking-related oral and pharyngeal cancers.
        Int J Cancer. 1999; 81: 44-48
        • Nair U.J.
        • Nair J.
        • Mathew B.
        • Bartsch H.
        Glutathione S-transferase M1 and T1 genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers.
        Carcinogenesis. 1999; 20: 743-748
        • Sikdar N.
        • Paul R.R.
        • Roy B.
        Glutathione S-transferase M3 (A/A) genotype as a risk factor for oral cancer and leukoplakia among Indian tobacco smokers.
        Int J Cancer. 2004; 109: 95-101
        • Matthias C.
        • Jahnke V.
        • Jones P.W.
        • et al.
        Cyclin D1, glutathione S-transferase and cytochrome P450 genotypes and outcome in patients with upper aerodigestive tract cancers: assessment of the importance of individual genes using multivariate analysis.
        Cancer Epidemiol Biomarkers Prev. 1999; 8: 815-823
        • Palli D.
        • Saieva C.
        • Gemma S.
        • et al.
        GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high risk Italian population.
        Int J Cancer. 2005; 115: 284-289
        • Hunter D.J.
        • Hankinson S.E.
        • Hough H.
        • et al.
        A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer.
        Carcinogenesis. 1997; 18: 2127-2132
        • Deng Y.
        • Newman B.
        • Dunne M.P.
        • Silburn P.A.
        • Mellick G.D.
        Case-only study of interactions between genetic polymorphisms of GSTM1, P1, T1 and Z1 and smoking in Parkinson’s disease.
        Neurosci Lett. 2004; 66: 326-331
        • Greenland S.
        The effect of misclassification in the presence of covariates.
        Am J Epidemiol. 1980; 112: 564-569
        • Ferenczy A.
        • Franco E.
        Persistent human papillomavirus infection and cervical neoplasia.
        Lancet Oncol. 2002; 3: 11-16
        • Chen C.
        • Nirunsuksiri1 W.
        Decreased expression of glutathione S-transferase M1 in HPV16- transfected human cervical keratinocytes in culture.
        Carcinogenesis. 1999; 20: 699-703