DOI QR코드

DOI QR Code

Glutathione S-transferase M1 and T1 Polymorphisms, Cigarette Smoking and HPV Infection in Precancerous and Cancerous Lesions of the Uterine Cervix

  • Sharma, Anita (Division of Molecular Diagnostics, Institute of Cytology and Preventive Oncology) ;
  • Gupta, Sanjay (Division of Cytopathology, Institute of Cytology and Preventive Oncology) ;
  • Sodhani, Pushpa (Division of Cytopathology, Institute of Cytology and Preventive Oncology) ;
  • Singh, Veena (Division of Clinical Oncology, Institute of Cytology and Preventive Oncology) ;
  • Sehgal, Ashok (Division of Epidemiology and Biostatistics, Institute of Cytology and Preventive Oncology) ;
  • Sardana, Sarita (Division of Epidemiology and Biostatistics, Institute of Cytology and Preventive Oncology) ;
  • Mehrotra, Ravi (Institute of Cytology and Preventive Oncology) ;
  • Sharma, Joginder Kumar (Division of Molecular Diagnostics, Institute of Cytology and Preventive Oncology)
  • Published : 2015.10.06

Abstract

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned to evaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures. Differences in proportions were tested using Pearson's Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes was observed in women with normal, precancerous and cervical cancerous lesions among ${\leq}35$ or >35 years of age groups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervical cancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non smokers. The results demonstrate that the GST null genotypes were alone not associated with the development of cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.

Keywords

Cervical cancer;GST polymorphisms;GSTM1;GSTT1;smoking;Pap smear;HPV

References

  1. Abbas M, Srivastava K, Imran M, Banerjee M (2013). Association of Glutathione S-transferase (GSTM1, GSTT1and GSTP1) polymorphisms and passive smoking in cervical cancer cases from North India. Int J Biomed Res, 4, 655-62. https://doi.org/10.7439/ijbr.v4i12.396
  2. Agodi A, Barchitta M, Cipresso R, et al (2010). Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical intraepithelial lesions in sicily. Int J Gynecol Cancer, 20, 141-6. https://doi.org/10.1111/IGC.0b013e3181c20842
  3. Agorastos T, Papadopoulos N, Lambropoulos AF, et al (2007). Glutathione-S-transferase M1 and T1 and cytochrome P1A1 genetic polymorphisms and susceptibility to cervical intraepithelial neoplasia in Greek women. Eur J Cancer Prev, 16, 498-504. https://doi.org/10.1097/01.cej.0000243859.99265.92
  4. Anantharaman D, Chaubal PM, Kannan S, Bhisey RA, Mahimkar MB (2007). Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator. Carcinogenesis, 28, 1455-62. https://doi.org/10.1093/carcin/bgm038
  5. Arand M, Muhlbauer R, Hengstler J, et al (1996). A multiplex polymerase chain reaction protocol for the simultaneous analysis of the glutathione S-transferase GSTM1 and GSTT1 polymorphisms. Anal Biochem, 236, 184-6. https://doi.org/10.1006/abio.1996.0153
  6. Arora R, Kumar A, Prusty BK, et al (2005). Prevalence of highrisk human papillomavirus (HR-HPV) types 16 and 18 in healthy women with cytologically negative Pap smear. Eur J Obstet Gynecol Reprod Biol, 121, 104-9. https://doi.org/10.1016/j.ejogrb.2004.11.025
  7. Au WW. (2004). Life style, environmental and genetic susceptibility to cervical cancer. Toxicol, 198, 117-20. https://doi.org/10.1016/j.tox.2004.01.022
  8. Au WW, Sierra-Torres CH, Tyring SK (2003). Acquired and genetic susceptibility to cervical cancer. Mutat Res, 544, 361-4. https://doi.org/10.1016/j.mrrev.2003.05.001
  9. Ben Salah G, Kallabi F, Maatoug S, et al (2012). Polymorphisms of glutathione S-transferases M1, T1, P1 and A1 genes in the tunisian population: an intra and interethnic comparative approach. Gene, 498, 317-22. https://doi.org/10.1016/j.gene.2012.01.054
  10. Beray K, Mutlu K, Hakan O, et al (2010). GST (GSTM1, GSTT1, and GSTP1) polymorphisms in the genetic susceptibility of Turkish patients to cervical cancer. J Gynecol Oncol, 21, 169-73. https://doi.org/10.3802/jgo.2010.21.3.169
  11. Chen C, Madeleine MM, Weiss NS, Daling JR (1999). Glutathione S-transferase M1 genotypes and the risk of squamous carcinoma of the cervix: a population-based casecontrol study. Am J Epidemiol, 150, 568-72. https://doi.org/10.1093/oxfordjournals.aje.a010054
  12. Chen C, Nirunsuksiri W (1999). Decreased expression of glutathione S-transferase M1 in HPV16-transfected human cervical keratinocytes in culture. Carcinogenesis, 20, 699-703. https://doi.org/10.1093/carcin/20.4.699
  13. Cseh J, Pazsit E, Orsos Z, et al (2011). Effect of glutathione-S-transferase M1 and T1 allelic polymorphisms on HPVinduced cervical precancer formation. Anticancer Res, 31, 3051-5.
  14. de Carvalho CR, da Silva ID, Pereira JS, et al (2008). Polymorphisms of p53, GSTM1 and GSTT1, and HPV in uterine cervix adenocarcinoma. Eur J Gynaecol Oncol, 29, 590-3.
  15. Economopoulos KP, Choussein S, Vlahos NF, Sergentanis TN (2010). GSTM1 polymorphism, GSTT1 polymorphism, and cervical cancer risk: a meta-analysis. Int J Gynecol Cancer, 20, 1576-80.
  16. Ferlay J, Soerjomataram I, Ervik M, et al (2013). Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11(Internet). GLOBOCAN 2012 v1. 0: International Agency for Research on Cancer, Lyon, France.
  17. Gao LB, Pan XM, Li LJ, et al (2011). Null genotypes of GSTM1 and GSTT1 contribute to risk of cervical neoplasia: an evidence-based meta-analysis. PLoS One, 6, 20157. https://doi.org/10.1371/journal.pone.0020157
  18. Giuliano AR, Sedjo RL, Roe DJ, et al (2002). Clearance of oncogenic human papillomavirus (HPV) infection: effect of smoking (United States). Cancer Causes Control, 13, 839-46. https://doi.org/10.1023/A:1020668232219
  19. Goodman MT, McDuffie K, Hernandez B, et al (2001). CYP1A1, GSTM1, and GSTT1 polymorphisms and the risk of cervical squamous intraepithelial lesions in a multiethnic population. Gynecol Oncol, 81, 263-9. https://doi.org/10.1006/gyno.2001.6154
  20. Hengstler JG, Arand M, Herrero ME, Oesch F (1998). Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. Recent Results Cancer Res, 154, 47-85. https://doi.org/10.1007/978-3-642-46870-4_4
  21. Huang K, Sandler R, Milikan RC, et al (2006). GSTM1 and GSTT1 polymorphisms, cigarette smoking, and risk of colon cancer: a population-based case-control study in North Carolina (United States). Cancer Causes Control, 17, 385-94. https://doi.org/10.1007/s10552-005-0424-1
  22. Jee SH, Lee JE, Kim S, Kim JH, Um SJ, Lee SJ, Namkoong SE, Park JS. (2002). GSTP1 polymorphism, cigarette smoking and cervical cancer risk in Korean women. Yonsei Med J, 43, 712-6. https://doi.org/10.3349/ymj.2002.43.6.712
  23. Joseph T, Chacko P, Wesley R, et al (2006). Germline genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes in Indian cervical cancer: associations with tumor progression, age and human papillomavirus infection. Gynecol Oncol, 101, 411-7. https://doi.org/10.1016/j.ygyno.2005.10.033
  24. Kietthubthew S, Sriplung H, Au WW (2001). Genetic and environmental interactions on oral cancer in Southern Thailand. Environ Mol Mutagen, 37, 111-6. https://doi.org/10.1002/em.1018
  25. Kim JW, Lee CG, Park YG, et al (2000). Combined analysis of germline polymorphisms of p53, GSTM1, GSTT1, CYP1A1, and CYP2E1: relation to the incidence rate of cervical carcinoma. Cancer, 88, 2082-91. https://doi.org/10.1002/(SICI)1097-0142(20000501)88:9<2082::AID-CNCR14>3.0.CO;2-D
  26. Kotaniemi-Talonen L, Anttila A, Malila N, et al (2008). Screening with a primary human papillomavirus test does not increase detection of cervical cancer and intraepithelial neoplasia 3. Eur J Cancer, 44, 565-71. https://doi.org/10.1016/j.ejca.2007.12.002
  27. Lee S, Cho S, Park S, Kim S, et al (2002). Combined effect of glutathione S-transferase M1 and T1 genotypes on bladder cancer risk. Cancer Lett, 177, 173. https://doi.org/10.1016/S0304-3835(01)00820-5
  28. Lee SA, Kim JW, Roh JW, et al (2004). Genetic polymorphisms of GSTM1, p21, p53 and HPV infection with cervical cancer in Korean women. Gynecol Oncol, 93, 14-8. https://doi.org/10.1016/j.ygyno.2003.11.045
  29. Liu Y, Ma W, Liu Q, et al (2009). Association between genetic polymorphism of GSTM1, CYP2E1 and susceptibility to cervical cancer and its precancerous lesions in Uighur women in Xinjiang. Prog Obstet Gynecol, 18, 840-3.
  30. Liu Y, Xu LZ (2012). Meta-analysis of association between GSTM1 gene polymorphism and cervical cancer. Asian Pac J Trop Med, 5, 480-4. https://doi.org/10.1016/S1995-7645(12)60083-2
  31. Ma C, Liu X, Ma Z. (2009). Association between genetic polymorphism of GSTM1 and susceptibility to cervical cancer in Uighur women in Xianjang. Chin J Obstet Gynecol, 44, 629-31.
  32. Mannervik B, Awasthi YC, Board PG, et al (1992). Nomenclature for human glutathione transferases. Biochem J, 282, 305-6. https://doi.org/10.1042/bj2820305
  33. Nishino K, Sekine M, Kodama S, et al (2008). Cigarette smoking and glutathione S-transferase M1 polymorphism associated with risk for uterine cervical cancer. J Obstet Gynaecol Res, 34, 994-1001.
  34. Niwa Y, Hirose K, Nakanishi T, et al (2005). Association of the NAD(P)H: quinone oxidoreductase C609T polymorphism and the risk of cervical cancer in Japanese subjects. Gynecol Oncol, 96, 423-9. https://doi.org/10.1016/j.ygyno.2004.10.015
  35. Palma S, Novelli F, Padua L, et al (2010). Interaction between glutathione-S-transferase polymorphisms, smoking habit, and HPV infection in cervical cancer risk. J Cancer Res Clin Oncol, 136, 1101-9. https://doi.org/10.1007/s00432-009-0757-3
  36. Prokopczyk B, Cox JE, Hoffmann D, Waggoner SE (1997). Identification of tobacco-specific carcinogen in the cervical mucus of smokers and nonsmokers. J Natl Cancer Inst, 89, 868-73. https://doi.org/10.1093/jnci/89.12.868
  37. 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.
  38. Risendal B, Dezapien J, Fowler B, Papenfuss M, Giuliano A (1999). Pap smear screening among urban SouthWestern American Indian women. Preve Med, 29, 510-8. https://doi.org/10.1006/pmed.1999.0565
  39. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S (2007). Human papillomavirus and cervical cancer. Lancet, 370, 890-907. https://doi.org/10.1016/S0140-6736(07)61416-0
  40. Schoell WMJ, Janicek MF, Mirhashemi R (1999). Epidemiology and biology of cervical cancer. Sem Surg Oncol, 16, 203-11. https://doi.org/10.1002/(SICI)1098-2388(199904/05)16:3<203::AID-SSU2>3.0.CO;2-C
  41. Settheetham-Ishida W, Youenyao P, Kularbkaew C, settheetham D, Ishida T (2009). Glutathione S-transferase (GSTM1 and GSTT1) polymorphisms in cervical cancer in Northeastern Thailand. Asian Pac J Cancer Prev, 10, 365-8.
  42. Sharma A, Pandey A, Sardana S, Sehgal S, Sharma JK (2012). Genetic polymorphisms of GSTM1 and GSTT1 genes in Delhi and comparison with other Indian and Global populations. Asian Pac J Cancer Prev, 13, 5647-52. https://doi.org/10.7314/APJCP.2012.13.11.5647
  43. Sharma A, Sharma JK, Murthy NS, Mitra AB (2004). Polymorphisms at GSTM1 and GSTT1 gene loci and susceptibility to cervical cancer in Indian population. Neoplasma, 51, 12-6.
  44. Sierra-Torres C, Au WW, Arrastia CD, et al (2003). Polymorphisms for chemical metabolizing genes and risk for cervical neoplasia. Environ Mol Mutagen, 41, 69-76. https://doi.org/10.1002/em.10132
  45. Sierra-Torres CH, Arboleda-Moreno YY, Orejuela-Aristizabal L (2006). Exposure to wood smoke, HPV infection, and genetic susceptibility for cervical neoplasia among women in Colombia. Environ Mol Mutagen, 47, 553-61. https://doi.org/10.1002/em.20228
  46. Singh H, Sachan R, Devi S, Pandey SN, Mittal B (2008). Association of GSTM1, GSTT1 and GSTM3 gene polymorphisms and susceptibility to cervical cancer in a North Indian population. Am J Obstet Gynecol, 198, 303.1-6.
  47. Sobti RC, Kaur S, Kaur P, et al (2006). Interaction of passive smoking with GST (GSTM1, GSTT1, and GSTP1) genotypes in the risk of cervical cancer in India. Cancer Genet Cytogenet, 166, 117-23. https://doi.org/10.1016/j.cancergencyto.2005.10.001
  48. Solomon D, Davey D, Kurman R, et al (2002). Forum group members; bethesda 2001 workshop.the 2001 bethesda system: terminology for reporting results of cervical cytology. JAMA, 287, 2114-9. https://doi.org/10.1001/jama.287.16.2114
  49. Song GY, Shao SL, Song ZY (2006). Association of single nucleotide polymorphism in glutathione S-transferase with susceptibility to cervical cancer (Chinese). Tumor J World, 5, 192-4.
  50. Spurdle AB, Webb PM, Purdie DM, et al (2001). Polymorphisms at the glutathione S-transferase GSTM1, GSTT1 and GSTP1 loci: risk of ovarian cancer by histological subtype. Carcinogenesis, 22, 67-72. https://doi.org/10.1093/carcin/22.1.67
  51. Stosic I, Grujicic D, Arsenijevic S, Brkic M, Milosevic-Djordjevic O (2014). Glutathione S-transferase T1 and M1 polymorphisms and risk of uterine cervical lesions in women from central Serbia. Asian Pac J Cancer Prev, 15, 3201-5. https://doi.org/10.7314/APJCP.2014.15.7.3201
  52. Sweeney C, Nazar-Stewart V, Stapleton P, Eaton D, Vaughan T (2003). Glutathione S-transferase M1, T1, and P1 polymorphisms and survival among lung cancer patients. Cancer Epidemiol Biomarkers Prev, 12, 527-33.
  53. Trimble CL, Genkinger JM, Burke AE, et al (2005). Active and passive cigarette smoking and the risk of cervical neoplasia. Obstet Gynecol, 105, 174-81. https://doi.org/10.1097/01.AOG.0000148268.43584.03
  54. Ueda M, Hung YC, Terai Y, et al (2005). Glutathione S-transferase and p53 polymorphisms in cervical carcinogenesis. Gynecol Oncol, 96, 736-40. https://doi.org/10.1016/j.ygyno.2004.11.005
  55. Ueda M, Toji E, Nunobiki O, et al (2008). Germline polymorphism of cancer susceptibility genes in gynecologic cancer. Hum Cell, 21, 95-104. https://doi.org/10.1111/j.1749-0774.2008.00058.x
  56. van der Hel OL, Peeters PH, Hein DW, et al (2003). NAT2 slow acetylation and GSTM1 null genotypes may increase postmenopausal breast cancer risk in long-term smoking women. Pharmacogenetics, 13, 399-407. https://doi.org/10.1097/00008571-200307000-00005
  57. Walboomers JM, Meijer CJ (1997). Do HPV-negative cervical carcinomas exist? J Pathol, 1281, 253-4.
  58. Wang D, Wang B, Zhai JX, Liu DW, Sun GG (2011). Glutathione S-transferase M1 and T1 polymorphisms and cervical cancer risk: a meta-analysis. Neoplasma, 58, 352-9. https://doi.org/10.4149/neo_2011_04_352
  59. Warwick A, Sarhanis P, Redman C, et al (1994). Theta class glutathione S-transferase GSTT1 genotypes and susceptibility to cervical neoplasia: interactions with GSTM1, CYP2D6 and smoking. Carcinogenesis, 15, 2841-5. https://doi.org/10.1093/carcin/15.12.2841
  60. Zhang ZY, Jin XY, Wu R, et al (2012). Meta-analysis of the association between GSTM1 and GSTT1 gene polymorphisms and cervical cancer. Asian Pac J Cancer Prev, 13, 815-9. https://doi.org/10.7314/APJCP.2012.13.3.815
  61. Zhen S, Hu C, Bian L (2013). Glutathione S-transferase polymorphism interactions with smoking status and HPV infection in cervical cancer risk: an evidence-based metaanalysis. PLoS One, 8, 83497. https://doi.org/10.1371/journal.pone.0083497
  62. Zhou Q, Wang J, Shao SL, MA XC, Ding L (2006). The association between glutathione S-transferase M1, T1polymorphisms and risk of cervical cancer. Modern Prevent Med, 33, 269-71.