Skip to main content

Advertisement

SpringerLink
Log in

Influence of NQO1, ALDH2, and CYP2E1 genetic polymorphisms, smoking, and alcohol drinking on the risk of lung cancer in Koreans

  • Original Paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Objectives

We investigated the association of genetic polymorphisms of NQO1, ALDH2, CYP2E1, and the combined genotype of these genes on lung cancer risk, and also evaluated the association after stratification by cumulative smoking amounts and alcohol drinking levels.

Methods

The case–control study was performed in 387 lung cancer patients and 387 age- and sex-matched cancer-free controls. Direct interview was conducted and the genotypes of NQO1, ALDH2, and CYP2E1 were investigated using PCR-RFLP or 5′-nuclease activity assay.

Results

The proportion of individuals with occupational history of mining was significantly higher in cases than in controls. The risk of lung cancer was significantly lower in light-drinkers (<108 g/week) than non-drinkers. The NQO1 Pro/Ser + Ser/Ser genotype showed an increased risk for lung cancer with a marginal significance (OR = 1.35, 95% CI = 0.99–1.86) compared with NQO1 Pro/Pro genotype. In heavy-smokers, the combination of NQO1 Pro/Ser + Ser/Ser and CYP2E1 c1/c1 genotype was associated with a significantly increased risk for lung cancer (OR = 2.25, 95% CI = 1.14–4.43) compared with those of NQO1 Pro/Pro and CYP2E1 c1/c2 + c2/c2 genotype. We found a significant interaction between alcohol drinking level and the CYP2E1 genotype (P = 0.0227).

Conclusions

Our result suggests that the risk of lung cancer is affected by smoking, alcohol drinking, and the genetic polymorphism of NQO1. In particular, genetic polymorphisms for NQO1, CYP2E1, and ALDH2 synergistically with cumulative smoking amounts and alcohol drinking levels interact in the carcinogenesis of lung cancer in Koreans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kuper H, Adami HO, Boffetta P (2002) Tobacco use, cancer causation and public health impact. J Intern Med 251:455–466. doi:10.1046/j.1365-2796.2002.00993.x

    Article  PubMed  CAS  Google Scholar 

  2. Peto R, Lopez AD, Boreham J, Thun M, Heath C Jr, Doll R (1996) Mortality from smoking worldwide. Br Med Bull 52:12–21

    PubMed  CAS  Google Scholar 

  3. Beckett WS (1993) Epidemiology and etiology of lung cancer. Clin Chest Med 14:1–15

    PubMed  CAS  Google Scholar 

  4. Daly AK, Cholerton S, Armstrong M, Idle JR (1994) Genotyping for polymorphisms in xenobiotic metabolism as a predictor of disease susceptibility. Environ Health Perspec 102:55–61

    Google Scholar 

  5. Ross D, Kepa JK, Winski SL, Beall HD, Anwar A, Siegel D (2000) NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chem Biol Interact 129:77–97. doi:10.1016/S0009-2797(00)00199-X

    Article  PubMed  CAS  Google Scholar 

  6. Traver RD, Siegel D, Beall HD et al (1997) Characterization of a polymorphism in NAD(P)H:quinone oxidoreductase (DT-diaphorase). Br J Cancer 75:69–75

    PubMed  CAS  Google Scholar 

  7. Paul N, John DH (2004) Contribution of NAD(P)H:quinone oxidoreductase 1 to protection against carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription factors. Mutation Res 555:149–171. doi:10.1016/j.mrfmmm.2004.05.023

    Google Scholar 

  8. Gasdaska PY, Powis G, Hyman P, Fisher H (1993) Cigarette smoking is a determinant of DT-diphorase gene expression in human non-small cell lung carcinoma. Cancer Res 53:5458–5461

    PubMed  CAS  Google Scholar 

  9. Kuehl BL, Paterson JW, Peacock JW, Paterson MC, Rauth AM (1995) Presence of a heterozygous substitution and its relationship to DT-diaphorase activity. Br J Cancer 72:555–561

    PubMed  CAS  Google Scholar 

  10. Enomoto N, Takase S, Yasuhara M, Takada A (1991) Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes. Alcohol Clin Exp Res 15:141–144. doi:10.1111/j.1530-0277.1991.tb00532.x

    Article  PubMed  CAS  Google Scholar 

  11. Harada S (1989) Polymorphism of aldehyde dehydrogenase and its application to alcoholism. Electrophoresis 10:652–655. doi:10.1002/elps.1150100820

    Article  PubMed  CAS  Google Scholar 

  12. Koop DR (1992) Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J 6:724–730

    PubMed  CAS  Google Scholar 

  13. Guengerich FP, Kim DH, Iwasaki M (1991) Role of cytochrome P450IIEI in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 4:168–179. doi:10.1021/tx00020a008

    Article  PubMed  CAS  Google Scholar 

  14. Hayashi S, Watanabe J, Kawajiri K (1991) Genetic polymorphisms in the 5′-flanking region change transcriptional regulation of the human cytochrome P450IIEI gene. J Biochem (Tokyo) 110:559–565

    CAS  Google Scholar 

  15. Agarwal DP (2001) Genetic polymorphisms of alcohol metabolizing enzymes. Pathol Biol 49:703–709. doi:10.1016/S0369-8114(01)00242-5

    Article  PubMed  CAS  Google Scholar 

  16. Gresner P, Gromadzinska J, Wasowicz W (2007) Polymorphism of selected enzymes involved in detoxification and biotransformation in relation to lung cancer. Lung Cancer 57:1–25. doi:10.1016/j.lungcan.2007.02.002

    Article  PubMed  Google Scholar 

  17. Saldivar SJ, Wang Y, Zhao H, Shao L, Lin J, Spitz MR, Wu X (2005) An association between a NQO1 genetic polymorphism and risk of lung cancer. Mutat Res 582:71–78

    PubMed  CAS  Google Scholar 

  18. Li LX, John CW, David PM et al (2001) The NAD(P)H:quinone Oxidoreductase 1 Gene Polymorphism and Lung Cancer: Differential Susceptibility Based on Smoking Behavior1. Cancer Epidemiol Biomarkers Prev 10:303–309

    CAS  Google Scholar 

  19. Yin L, Pu Y, Liu TY, Tung YH, Chen KW, Lin P (2001) Genetic polymorphisms of NAD(P)H quinine oxidoreductase, CYP1A1 and microsomal epoxide hydrolase and lung cancer risk in Nanjing, China. Lung Cancer 33:133–141. doi:10.1016/S0169-5002(01)00182-9

    Article  PubMed  CAS  Google Scholar 

  20. Vineis P, Veglia F, Garte S et al (2007) Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers. Ann Oncol 18:1230–1242. doi:10.1093/annonc/mdm109

    Article  PubMed  CAS  Google Scholar 

  21. Lewis SJ, Cherry NM, Niven RM, Barber PV, Povey AC (2001) Polymorphisms in the NAD(P)H: quinone oxidoreductase gene and small cell lung cancer risk in a UK population. Lung Cancer 34:177–183. doi:10.1016/S0169-5002(01)00243-4

    Article  PubMed  CAS  Google Scholar 

  22. Sunaga N, Kohno T, Yanagitani N et al (2002) Contribution of the NQO1 and GSTT1 polymorphisms to lung adenocarcinoma susceptibility. Cancer Epidemiol Biomarkers Prev 11:730–738

    PubMed  CAS  Google Scholar 

  23. Chao C, Zhang ZF, Berthiller J, Boffetta P, Hashibe M (2006) NAD(P)H:quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and the risk of lung, bladder, and colorectal cancers: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15:979–987. doi:10.1158/1055-9965.EPI-05-0899

    Article  PubMed  CAS  Google Scholar 

  24. Yang M, Choi Y, Hwangbo B, Lee JS (2007) Combined effects of genetic polymorphisms in six selected genes on lung cancer susceptibility. Lung Cancer 57:135–142. doi:10.1016/j.lungcan.2007.03.005

    Article  PubMed  Google Scholar 

  25. Bock CH, Wenzlaff AS, Cote ML, Land SJ, Schwartz AG (2005) NQO1 T allele associated with decreased risk of later age at diagnosis lung cancer among never smokers: results from a population-based study. Carcinogenesis 26:381–386. doi:10.1093/carcin/bgh314

    Article  PubMed  CAS  Google Scholar 

  26. Wang SL, Lee H, Chen KW, Tsai KJ, Chen CY, Lin P (1999) Cytochrome P4502E1 genetic polymorphisms and lung cancer in a Taiwanese population. Lung Cancer 26:27–34. doi:10.1016/S0169-5002(99)00070-7

    Article  PubMed  CAS  Google Scholar 

  27. Wang J, Deng Y, Li L et al (2003) Association of GSTM1, CYP1A1 and CYP2E1 genetic polymorphisms with susceptibility to lung adenocarcinoma: a case-control study in Chinese population. Cancer Sci 94:448–452. doi:10.1111/j.1349-7006.2003.tb01463.x

    Article  PubMed  CAS  Google Scholar 

  28. Marchand LL, Wilkinson GR, Wilkens LR (1999) Genetic and dietary predictors of CYP2E1 activity: a phenotyping study in Hawaii Japanese using chlorzoxazone. Cancer Epidemiol Biomarkers Prev 8:495–500

    PubMed  CAS  Google Scholar 

  29. Kim RB, Yamazaki H, Chiba K et al (1996) In vivo and in vitro characterization of CYP2E1 activity in Japanese and Caucasians. J Pharmacol Exp Ther 279:4–11

    PubMed  CAS  Google Scholar 

  30. Tampo Y, Yonaha M (1996) Enzymatic and molecular aspects of the antioxidant effect of menadione in hepatic microsomes. Arch Biochem Biophys 334:163–174. doi:10.1006/abbi.1996.0442

    Article  PubMed  CAS  Google Scholar 

  31. Radjendirane V, Joseph P, Lee YH et al (1998) Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity. J Biol Chem 273:7382–7389. doi:10.1074/jbc.273.13.7382

    Article  PubMed  CAS  Google Scholar 

  32. Chen W, Koenigs LL, Thompson SJ et al (1998) Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6. Chem Res Toxicol 11:295–301. doi:10.1021/tx9701687

    Article  PubMed  CAS  Google Scholar 

  33. Gao Q, Doneanu CE, Shaffer SA, Adman ET, Goodlett DR, Nelson SD (2006) Identification of the interactions between cytochrome P450 2E1 and cytochrome b5 by mass spectrometry and site-directed mutagenesis. J Biol Chem 281:20404–20417. doi:10.1074/jbc.M601785200

    Article  PubMed  CAS  Google Scholar 

  34. Bandera EV, Freudenheim JL, Vena JE (2001) Alcohol consumption and lung cancer: a review of the epidemiologic evidence. Cancer Epidemiol Biomarkers Prev 10:813–821

    PubMed  CAS  Google Scholar 

  35. Bandera EV, Freudenheim JL, Marshall JR et al (1997) Diet and alcohol consumption and lung cancer risk in the New York State Cohort (United States). Cancer Causes Control 8:819–820. doi:10.1023/A:1018456127018

    Article  Google Scholar 

  36. Kono S, Ikeda M, Tokudome S, Nishizume M, Kuratsune M (1986) Alcohol and mortality: a cohort study of mele Japanses physicians. Int J Epidemiol 15:527–532. doi:10.1093/ije/15.4.527

    Article  PubMed  CAS  Google Scholar 

  37. Prescott E, Gronbaek M, Becker U, Sorensen TIA (1999) Alcohol intake and risk of lung cancer: influence of type of alcoholic beverage. Am J Epidemiol 149:463–470

    PubMed  CAS  Google Scholar 

  38. De Stefani E, Correa P, Deneo-Pellegrini H (2002) Alcohol intake and risk of adenocarcinoma of the lung: a case-control study in Uruguay. Lung Cancer 38:9–14. doi:10.1016/S0169-5002(02)00153-8

    Article  PubMed  Google Scholar 

  39. Hori H, Kawano T, Endo M, Yuasa Y (1997) Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and human esophageal squamous cell carcinoma susceptibility. J Clin Gastroenterol 25:568–575. doi:10.1097/00004836-199712000-00003

    Article  PubMed  CAS  Google Scholar 

  40. Yokoyama T, Yokoyama A, Kato H et al (2003) Alcohol flushing, alcohol and aldehyde dehydrogenase genotypes, and risk for esophageal squamous cell carcinoma in Japanese men. Cancer Epidemiol Biomarkers Prev 12:1227–1233

    PubMed  CAS  Google Scholar 

  41. Yokoyama A, Muramatsu T, Ohmori T et al (1998) Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics. Carcinogenesis 19:1383–1387. doi:10.1093/carcin/19.8.1383

    Article  PubMed  CAS  Google Scholar 

  42. Minegishi Y, Tsukino H, Muto M et al (2007) Susceptibility to lung cancer and genetic polymorphisms in the alcohol metabolite-related enzymes alcohol dehydrogenase 3, aldehyde dehydrogenase 2, and cytochrome P450 2E1 in the Japanese population. Cancer 110:353–362. doi:10.1002/cncr.22795

    Article  PubMed  CAS  Google Scholar 

  43. Yang M, Coles BF, Delongchamp R, Lang NP, Kadlubar FF (2002) Effects of the ADH3, CYP2E1, and GSTP1 genetic polymorphisms on their expressions in Caucasian lung tissue. Lung Cancer 38:15–21. doi:10.1016/S0169-5002(02)00150-2

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Eco-technopia 21 project of Ministry of Environment, South Korea.

Author information

Authors and Affiliations

  1. Department of Preventive Medicine, College of Medicine, Chungbuk National University, 12 Gaeshin-dong, Heungdok-gu, Cheongju, Chungbuk, 361-763, Republic of Korea

    Sang-Yong Eom, Yan Wei Zhang, Sung-Hoon Kim, Yong-Dae Kim, Jong-Won Kang & Heon Kim

  2. Department of Internal Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea

    Kang-Hyeon Choe

  3. Department of Internal Medicine College of Medicine, Konkuk University, Seoul, Republic of Korea

    Kye Young Lee

  4. Department of Preventive Medicine, College of Medicine, Chungang University, Seoul, Republic of Korea

    Jung-Duck Park

  5. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

    Yun-Chul Hong

Authors
  1. Sang-Yong Eom
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sung-Hoon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kang-Hyeon Choe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kye Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jung-Duck Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yun-Chul Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yong-Dae Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jong-Won Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Heon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heon Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eom, SY., Zhang, Y.W., Kim, SH. et al. Influence of NQO1, ALDH2, and CYP2E1 genetic polymorphisms, smoking, and alcohol drinking on the risk of lung cancer in Koreans. Cancer Causes Control 20, 137–145 (2009). https://doi.org/10.1007/s10552-008-9225-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-008-9225-7

Keywords

Search

Navigation