Skip to main content
Cancer Science logoLink to Cancer Science
. 2005 Aug 19;94(5):448–452. doi: 10.1111/j.1349-7006.2003.tb01463.x

Association of GSTM1, CYP1A1 and CYP2E1 genetic polymorphisms with susceptibility to lung adenocarcinoma: A case‐control study in Chinese population

Jingwen Wang 1, Yifu Deng 1, Li Li 2, Kiyonori Kuriki 1, Jianmin Ding 3, Xiaochun Pan 5, Xin Zhuge 6, Jing Jiang 1, Chenhong Luo 4, Peng Lin 2, Shinkan Tokudome 1,
PMCID: PMC11160285  PMID: 12824892

Abstract

A case‐control study of 164 lung adenocarcinoma (AC) patients with 181 age‐ and gender‐matched healthy controls was conducted in order to assess any associations between glutathione‐S‐transferase M1 (GSTM1), cytochrome P4501A1 (CYP1A1) and cyto‐chrome P4502E1 (CYP2E1) polymorphisms and susceptibility to lung AC in Chinese. The presence of CYP2E1 variant allele was significantly less frequent in cases than in controls, while the distribution of GSTM1 null genotype and variant CYP1A1 Msp1 allele did not vary between cases and controls. After adjustment for age, gender, smoking and all other genotypes, the CYP2E1 Rsa1 variant allele was significantly associated with decreased risk of lung AC [odds ratio 0.534 (95% confidence interval, 0.340–0.837)]. Furthermore, 3.0‐fold increased risk was found in individuals with combined GSTM1 null genotype and CYP2E1 Rsa1 wild type versus those with combined GSTM1 non‐null type and CYP2E1 variant allele. Our results suggest that CYP2E1 Rsa1 variant allele is associated with a decreased risk of lung AC, and combined GSTM1 null genotype and CYP2E1 Rsa1 wild type has a promoting effect on susceptibility to lung AC. (Cancer Sci 2003; 94: 448–452)

References

  • 1. Hoffman PC, Mauer AM, Yokes EE. Lung cancer. Lancet 2000; 355: 479–85. [DOI] [PubMed] [Google Scholar]
  • 2. Osann KE. Epidemiology of lung cancer. Curr Opin Pulm Med 1998; 4: 198–204. [DOI] [PubMed] [Google Scholar]
  • 3. Alexandrie AK, Sundberg MI, Seidegard J, Tornling G, Rannug A. Genetic susceptibility to lung cancer with special emphasis on CYP1A1 and GSTM1: a study on host factors in relation to age at onset, gender and histological cancer types. Cardnogenesis 1994; 15: 1785–90. [DOI] [PubMed] [Google Scholar]
  • 4. Ford JG, Li Y, O'Sullivan MM, Demopoulos R, Garte S, Taioli E, Brandt‐Rauf PW. Glutathione S‐transferase Ml polymorphism and lung cancer risk in African‐Americans. Cardnogenesis 2000; 21: 1971–5. [DOI] [PubMed] [Google Scholar]
  • 5. Garcia‐Closas M, Kelsey KT, Wiencke JK, Xu X, Wain JC, Christiani DC. A case‐control study of cytochrome P450 1A1, glutathione S‐transferase Ml, cigarette smoking and lung cancer susceptibility (Massachusetts, United States). Cancer Causes Control 1997; 8: 544–53. [DOI] [PubMed] [Google Scholar]
  • 6. Le Marchand L, Sivaraman L, Pierce L, Seifried A, Lum A, Wilkens LR, Lau AF. Associations of CYP1A1, GSTM1, and CYP2E1 polymorphisms with lung cancer suggest cell type specificities to tobacco carcinogens. Cancer Res 1998; 58: 4858–63. [PubMed] [Google Scholar]
  • 7. Lin P, Wang SL, Wang HJ, Chen KW, Lee HS, Tsai KJ, Chen CY, Lee H. Association of CYP1A1 and microsomal epoxide hydrolase polymorphisms with lung squamous cell carcinoma. Er J Cancer 2000; 82: 852–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Okada T, Kawashima K, Fukushi S, Minakuchi T, Nishimura S. Association between a cytochrome P450 CYPIA1 genotype and incidence of lung cancer. Pharmacogenetics 1994; 4: 333–40. [DOI] [PubMed] [Google Scholar]
  • 9. Song N, Tan W, Xing D, Lin D. CYP 1A1 polymorphism and risk of lung cancer in relation to tobacco smoking: a case‐control study in China. Carcinogenesis 2001; 22: 11–6. [DOI] [PubMed] [Google Scholar]
  • 10. Sugimura H, Wakai K, Genka K, Nagura K, Igarashi H, Nagayama K, Ohkawa A, Baba S, Morris BJ, Tsugane S, Ohno Y, Gao C, Li Z, Takezaki T, Tajima K, Iwamasa T. Association of Ile462Val (Exon 7) polymorphism of cytochrome P450 1A1 with lung cancer in the Asian population: further evidence from a case‐control study in Okinawa. Cancer Epidemiol Biomarkers Prev 1998; 7: 413–7. [PubMed] [Google Scholar]
  • 11. Xu X, Kelsey KT, Wiencke JK, Wain JC, Christiant DC. Cytochrome P450 CYP1A1 MspI polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev 1996; 5: 687–92. [PubMed] [Google Scholar]
  • 12. Hirvonen A, Husgafvel‐Pursiainen K, Anttila S, Karjalainen A, Vainio H. The human CYP2E1 gene and lung cancer: Dral and Rsal restriction fragment length polymorphisms in a Finnish study population. Carcinogenesis 1993; 14: 85–8. [DOI] [PubMed] [Google Scholar]
  • 13. Kato S, Shields PG, Caporaso NE, Hoover RN, Trump BF, Sugimura H, Weston A, Harris CC. Cytochrome P450IIE1 genetic polymorphisms, racial variation, and lung cancer risk. Cancer Res 1992; 52: 6712–5. [PubMed] [Google Scholar]
  • 14. Kato S, Shields PG, Caporaso NE, Sugimura H, Trivers GE, Tucker MA, Trump BF, Weston A, Harris CC. Analysis of cytochrome P450 2E1 genetic polymorphisms in relation to human lung cancer. Cancer Epidemiol Biomarkers Prev 1994; 3: 515–8. [PubMed] [Google Scholar]
  • 15. Li Z, Tan W, Shao K. Susceptibility to lung cancer in Chinese is associated with genetic polymorphism in cytochrome P4502E1. Zhonghua Zhong Liu Za Zhi 2000; 22: 5–7 (in Chinese). [PubMed] [Google Scholar]
  • 16. Persson I, Johansson I, Bergling H, Dahl ML, Seidegard J, Rylander R, Rannug A, Hogberg J, Sundberg MI. Genetic polymorphism of cytochrome P4502E1 in a Swedish population. Relationship to incidence of lung cancer. FEBS Lett 1993; 319: 207–11. [DOI] [PubMed] [Google Scholar]
  • 17. Persson I, Johansson I, Lou YC, Yue QY, Duan LS, Bertilsson L, Ingelman‐Sundberg M. Genetic polymorphism of xenobiotic metabolizing enzymes among Chinese lung cancer patients. Int J Cancer 1999; 81: 325–9. [DOI] [PubMed] [Google Scholar]
  • 18. Quiñones L, Lucas D, Godoy J, Cáceres D, Berthou F, Varela N, Lee K, Acevedo C, Martínez L, Aguilera AM, Gil L. CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people. Cancer Lett 2001; 174: 35–44. [DOI] [PubMed] [Google Scholar]
  • 19. Wang SL, Lee H, Chen KW, Tsai KJ, Chen CY, Lin P. Cytochrome P4502E1 genetic polymorphisms and lung cancer in a Taiwanese population. Lung Cancer 1999; 26: 27–34. [DOI] [PubMed] [Google Scholar]
  • 20. Watanabe J, Yang JP, Eguchi H, Hayashi S, Imai K, Nakachi K, Kawajiri K. An Rsa I polymorphism in the CYP2E1 gene does not affect lung cancer risk in a Japanese population. Jpn J Cancer Res 1995; 86: 245–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Wu X, Shi H, Jiang H, Kemp B, Hong WK, Delclos GL, Spitz MR. Associations between cytochrome P4502E1 genotype, mutagen sensitivity, cigarette smoking and susceptibility to lung cancer. Carcinogenesis 1997; 18: 967–73. [DOI] [PubMed] [Google Scholar]
  • 22. Wu X, Amos CI, Kemp BL, Shi H, Jiang H, Wan Y, Spitz MR. Cytochrome P450 2E1 Dral polymorphisms in lung cancer in minority populations. Cancer Epidemiol Biomarkers Prev 1998; 7: 13–8. [PubMed] [Google Scholar]
  • 23. Cha Q, Chen Y, Du Y. The trends in histological types of lung cancer during 1980–1988, Guangzhou, China. Lung Cancer 1997; 17: 219–30. [DOI] [PubMed] [Google Scholar]
  • 24. Blin N, Stafford DW. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res 1976; 3: 2303–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Bell DA, Thompson CL, Taylor J, Miller CR, Perera F, Hsieh LL, Lucier GW. Genetic monitoring of human polymorphic cancer susceptibility genes by polymerase chain reaction: application to glutathione transferase mu. Environ Health Perspect 1992; 98: 113–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Lum A, Le Marchand L. A simple mouthwash method for obtaining ge‐nomic DNA in molecular epidemiological studies. Cancer Epidemiol Biomarkers Prev 1998; 7: 719–24. [PubMed] [Google Scholar]
  • 27. Hayashi S, Watanabe J, Kawajiri K. Genetic polymorphisms in the 5′‐flank‐ing region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem (Tokyo) 1991; 110: 559–65. [DOI] [PubMed] [Google Scholar]
  • 28. Kim RB, O'Shea D, Wilkinson GR. Relationship in healthy subjects between CYP2E1 genetic polymorphisms and the 6‐hydroxylation of chlorzoxazone: a putative measure of CYP2E1 activity. Pharmacogenetics 1994; 4: 162–5. [PubMed] [Google Scholar]
  • 29. Gao Y, Zhang Q. Polymorphisms of the GSTM1 and CYP2D6 genes associated with susceptibility to lung cancer in Chinese. Mutat Res 1999; 444: 441–9. [DOI] [PubMed] [Google Scholar]
  • 30. Lan Q, He X, Costa DJ, Tian L, Rothman N, Hu G, Mumford JL. Indoor coal combustion emissions, GSTM1 and GSTT1 genotypes, and lung cancer risk: a case‐control study in Xuan Wei, China. Cancer Epidemiol Biomarkers Prev 2000; 9: 605–8. [PubMed] [Google Scholar]
  • 31. Sun GF, Shimojo N, Pi JB, Lee S, Kumagai Y. Gene deficiency of glutathione S‐transferase mu isoform associated with susceptibility to lung cancer in a Chinese population. Cancer Lett 1997; 113: 169–72. [DOI] [PubMed] [Google Scholar]
  • 32. Wang AH, Sun CS, Li LS, Huang JY, Chen QS. Relationship of tobacco smoking, CYP1A1, GSTM1 gene polymorphism and esophageal cancer in Xi'an. World J Gastroenterol 2002; 8: 49–53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Yin L, Pu Y, Liu TY, Tung YH, Chen KW, Lin P. Genetic polymorphisms of NAD(P)H quinone oxidoreductase, CYP1A1 and microsomal epoxide hydrolase and lung cancer risk in Nanjing, China. Lung Cancer 2001; 33: 133–41. [DOI] [PubMed] [Google Scholar]
  • 34. Zhao B, Seow A, Lee EJ, Poh WT, Teh M, Eng P, Wang YT, Tan WC, Yu MC, Lee HP. Dietary isothiocyanates, glutathione S‐transferase‐M1, ‐T1 polymorphisms and lung cancer risk among Chinese women in Singapore. Cancer Epidemiol Biomarkers Prev 2001; 10: 1063–7. [PubMed] [Google Scholar]
  • 35. Vineis P, Bartsch H, Caporaso N, Harrington AM, Kadlubar FF, Landi MT, Malaveille C, Shields PG, Skipper P, Talaska G. Genetically based N‐acetyl‐transferase metabolic polymorphism and low‐level environmental exposure to carcinogens. Nature 1994; 369: 154–6. [DOI] [PubMed] [Google Scholar]
  • 36. Vineis P. Molecular epidemiology: low‐dose carcinogens and genetic susceptibility. Int J Cancer 1997; 71: 1–3. [DOI] [PubMed] [Google Scholar]
  • 37. Nair U, Bartsch H. Metabolic polymorphisms as susceptibility markers for lung and oral cavity cancer. IARC Sci Publ 2001; 154: 271–90. [PubMed] [Google Scholar]
  • 38. Reszka E, Wasowicz W. Significance of genetic polymorphisms in glutathione transferase multigene family and lung cancer risk. Int J Occup Med Environ Health 2001; 14: 99–113. [PubMed] [Google Scholar]
  • 39. McWilliams JE, Sanderson BJ, Harris EL, Richert‐Boe KE, Henner WD. Glutathione S‐transferase Ml (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomarkers Prev 1995; 4: 589–94. [PubMed] [Google Scholar]
  • 40. Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco‐related cancers. Cancer Epidemiol Biomarkers Prev 2000; 9: 3–28. [PubMed] [Google Scholar]
  • 41. Bellec G, Dreano Y, Lozach P, Menez JF, Berthou F. Cytochrome P450 metabolic dealkylation of nine N‐nitrosodialkylamines by human liver mi‐crosomes. Carcinogenesis 1996; 17: 2029–34. [DOI] [PubMed] [Google Scholar]
  • 42. Hecht SS, Hoffmann D. Tobacco‐specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke. Carcinogenesis 1988; 9: 875–84. [DOI] [PubMed] [Google Scholar]
  • 43. Hecht SS. Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 1999; 91: 1194–210. [DOI] [PubMed] [Google Scholar]
  • 44. Ekstrom G, Ingelman‐Sundberg M. Rat liver microsomal NADPH‐supported oxidase activity and lipid peroxidation dependent on ethanol‐inducible cytochrome P‐450 (P‐450IIE1). Biochem Pharmacol 1989; 38: 1313–9. [DOI] [PubMed] [Google Scholar]
  • 45. Uematsu F, Kikuchi H, Motomiya M, Abe T, Sagami I, Ohmachi T, Wakui A, Kanamaru R, Watanabe M. Association between restriction fragment length polymorphism of the human cytochrome P450IIE1 gene and susceptibility to lung cancer. Jpn J Cancer Res 1991; 82: 254–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. El Zein RA, Zwischenberger JB, Abdel‐Rahman SZ, Sankar AB, Au WW. Polymorphism of metabolizing genes and lung cancer histology: prevalence of CYP2E1 in adenocarcinoma. Cancer Lett 1997; 112: 71–8. [DOI] [PubMed] [Google Scholar]
  • 47. Oyama T, Kawamoto T, Mizoue T, Sugio K, Kodama Y, Mitsudomi T, Yasumoto K. Cytochrome P450 2E1 polymorphism as a risk factor for lung cancer: in relation to p53 gene mutation. Anticancer Res 1997; 17: 583–7. [PubMed] [Google Scholar]

Articles from Cancer Science are provided here courtesy of Wiley

RESOURCES