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Association between polymorphisms of biotransformation and DNA-repair genes and risk of colorectal cancer in Taiwan

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Journal of Biomedical Science

Abstract

The relationship between diet and colorectal cancer has been previously demonstrated and supported with strong epidemiological evidence. The role of genetic polymorphisms has, however, been less well elaborated upon. We conducted a hospital-based case–control study including 727 cases and 736 healthy controls to evaluate the associations of the polymorphic phase-I and -II biotransformations (CYP1A1, CYP1A2, GSTM1, GSTT1, GSTP1, NAT1 and NAT2) and DNA-repair enzymes (XRCC1, XRCC3 and XPD) with the risk of contracting colorectal cancer. We found that men featuring the CYP1A1*2C G/G genotype, the GSTT1 null genotype and XPD 751 with the Gln allele were associated with an elevated risk of colorectal cancer than were men who did not exhibit such genetic features. Multivariate logistic regression analysis revealed that individuals featuring more than two high-risk genotypes increased the colorectal-cancer risk 3.1-fold (OR = 3.1, 95% CI = 1.8–5.2). For women, subjects featuring the CYP1A1*2C G/G genotype and the XRCC3 Thr/Thr genotype faced a 3.1-fold greater risk (95% CI = 1.3–7.0) of colorectal cancer when compared to those featuring the CYP1A1*2C A allele and the XRCC3 Met allele. Taken together, this study suggests that polymorphisms of genes involved in biotransformation and DNA repair could modulate colorectal-cancer risk in Taiwan.

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References

  1. Potter J.D. (1992) Reconciling the epidemiology, physiology, and molecular biology of colon cancer. JAMA 268: 1573–1577

    Article  PubMed  CAS  Google Scholar 

  2. Potter J.D., Slattery M.L., Bostick R.M. and Gapstur S.M. (1993) Colon cancer: a review of the epidemiology. Epidemiol. Rev. 15: 499–545

    PubMed  CAS  Google Scholar 

  3. Fearon E.R. and Vogelstein B. (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759–767

    Article  PubMed  CAS  Google Scholar 

  4. Bodmer W.F., Bailey C.J., Bodmer J., Bussey H.J., Ellis A., Gorman P., Lucibello F.C., Murday V.A., Rider S.H., Scambler P. and et al. (1987) Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature 328: 614–616

    Article  PubMed  CAS  Google Scholar 

  5. Bronner C.E., Baker S.M., Morrison P.T., Warren G., Smith L.G., Lescoe M.K., Kane M., Earabino C., Lipford J., Lindblom A. and et al. (1994) Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368: 258–261

    Article  PubMed  CAS  Google Scholar 

  6. Houlston R.S. and Tomlinson I.P. (2001) Polymorphisms and colorectal tumor risk. Gastroenterology 121: 282–301

    Article  PubMed  CAS  Google Scholar 

  7. de Boer J.G. (2002) Polymorphisms in DNA repair and environmental interactions. Mutat. Res. 509: 201–210

    PubMed  Google Scholar 

  8. Gertig D.M. and Hunter D.J. (1998) Genes and environment in the etiology sof colorectal cancer. Semin. Cancer Biol. 8: 285–298

    Article  PubMed  CAS  Google Scholar 

  9. Perera F.P., Mooney L.A., Dickey C.P., Santella R.M., Bell D., Blaner W., Tang D. and Whyatt R.M. (1996) Molecular epidemiology in environmental carcinogenesis. Environ. Health Perspect. 104 (Suppl 3): 441–443

    Article  PubMed  Google Scholar 

  10. Raunio H., Husgafvel-Pursiainen K., Anttila S., Hietanen E., Hirvonen A. and Pelkonen O. (1995) Diagnosis of polymorphisms in carcinogen-activating and inactivating enzymes and cancer susceptibility – a review. Gene 159: 113–121

    Article  PubMed  CAS  Google Scholar 

  11. Kiyohara C. (2000) Genetic polymorphism of enzymes involved in xenobiotic metabolism and the risk of colorectal cancer. J. Epidemiol. 10: 349–360

    PubMed  CAS  Google Scholar 

  12. Kiss I., Sandor J., Pajkos G., Bogner B., Hegedus G. and Ember I. (2000) Colorectal cancer risk in relation to genetic polymorphism of cytochrome P450 1A1, 2E1, and glutathione-S-transferase M1 enzymes. Anticancer Res. 20: 519–522

    PubMed  CAS  Google Scholar 

  13. Ye Z. and Parry J.M. (2002) Genetic polymorphisms in the cytochrome P450 1A1, glutathione S-transferase M1 and T1, and susceptibility to colon cancer. Teratog. Carcinog. Mutagen. 22: 385–392

    Article  PubMed  CAS  Google Scholar 

  14. Turesky R.J., Lang N.P., Butler M.A., Teitel C.H. and Kadlubar F.F. (1991) Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon. Carcinogenesis 12: 1839–1845

    Article  PubMed  CAS  Google Scholar 

  15. Lang N.P., Butler M.A., Massengill J., Lawson M., Stotts R.C., Hauer-Jensen M. and Kadlubar F.F. (1994) Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps. Cancer Epidemiol. Biomark. Prev. 3: 675–682

    CAS  Google Scholar 

  16. Hou S.M., Falt S., Angelini S., Yang K., Nyberg F., Lambert B. and Hemminki K. (2002) The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis 23: 599–603

    Article  PubMed  CAS  Google Scholar 

  17. Matullo G., Guarrera S., Carturan S., Peluso M., Malaveille C., Davico L., Piazza A. and Vineis P. (2001) DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case–control study. Int. J. Cancer 92: 562–567

    Article  PubMed  CAS  Google Scholar 

  18. Hu J.J., Mohrenweiser H.W., Bell D.A., Leadon S.A. and Miller M.S. (2002) Symposium overview: genetic polymorphisms in DNA repair and cancer risk. Toxicol. Appl. Pharmacol. 185: 64–73

    Article  PubMed  CAS  Google Scholar 

  19. Braithwaite E., Wu X. and Wang Z. (1999) Repair of DNA lesions: mechanisms and relative repair efficiencies. Mutat. Res. 424: 207–219

    PubMed  CAS  Google Scholar 

  20. Butkiewicz D., Rusin M., Enewold L., Shields P.G., Chorazy M. and Harris C.C. (2001) Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis 22: 593–597

    Article  PubMed  CAS  Google Scholar 

  21. Matullo G., Palli D., Peluso M., Guarrera S., Carturan S., Celentano E., Krogh V., Munnia A., Tumino R., Polidoro S., Piazza A. and Vineis P. (2001) XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis 22: 1437–1445

    Article  PubMed  CAS  Google Scholar 

  22. Lunn R.M., Langlois R.G., Hsieh L.L., Thompson C.L. and Bell D.A. (1999) XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res. 59: 2557–2561

    PubMed  CAS  Google Scholar 

  23. Butler W.J., Ryan P. and Roberts-Thomson I.C. (2001) Metabolic genotypes and risk for colorectal cancer. J. Gastroenterol. Hepatol. 16: 631–635

    Article  PubMed  CAS  Google Scholar 

  24. Sachse C., Smith G., Wilkie M.J., Barrett J.H., Waxman R., Sullivan F., Forman D., Bishop D.T. and Wolf C.R. (2002) A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis 23: 1839–1849

    Article  PubMed  CAS  Google Scholar 

  25. Yoshioka M., Katoh T., Nakano M., Takasawa S., Nagata N. and Itoh H. (1999) Glutathione S-transferase (GST) M1, T1, P1, N-acetyltransferase (NAT) 1 and 2 genetic polymorphisms and susceptibility to colorectal cancer. J Uoeh 21: 133–147

    PubMed  CAS  Google Scholar 

  26. Kiss I., Nemeth A., Bogner B., Pajkos G., Orsos Z., Sandor J., Csejtey A., Faluhelyi Z., Rodler I. and Ember I. (2004) Polymorphisms of glutathione-S-transferase and arylamine N-acetyltransferase enzymes and susceptibility to colorectal cancer. Anticancer Res. 24: 3965–3970

    PubMed  CAS  Google Scholar 

  27. Yeh C.C., Hsieh L.L., Tang R., Chang-Chieh C.R. and Sung F.C. (2003) Risk factors for colorectal cancer in Taiwan: a hospital-based case–control study. J. Formos. Med. Assoc. 102: 305–312

    PubMed  Google Scholar 

  28. Hayashi S., Watanabe J., Nakachi K. and Kawajiri K. (1991) Genetic linkage of lung cancer-associated MspI polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene. J. Biochem. (Tokyo). 110: 407–411

    CAS  Google Scholar 

  29. Huang C.Y., Huang K.L., Cheng T.J., Wang J.D. and Hsieh L.L. (1997) The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function. Arch. Toxicol. 71: 482–488

    Article  PubMed  CAS  Google Scholar 

  30. Nakajima M., Yokoi T., Mizutani M., Kinoshita M., Funayama M. and Kamataki T. (1999) Genetic polymorphism in the 5′-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans. J. Biochem. (Tokyo) 125: 803–808

    CAS  Google Scholar 

  31. Harries L.W., Stubbins M.J., Forman D., Howard G.C. and Wolf C.R. (1997) Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 18: 641–644

    Article  PubMed  CAS  Google Scholar 

  32. Lunn R.M., Helzlsouer K.J., Parshad R., Umbach D.M., Harris E.L., Sanford K.K. and Bell D.A. (2000) XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis 21: 551–555

    Article  PubMed  CAS  Google Scholar 

  33. Bell D.A., Stephens E.A., Castranio T., Umbach D.M., Watson M., Deakin M., Elder J., Hendrickse C., Duncan H. and Strange R.C. (1995) Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases risk of colorectal cancer. Cancer Res. 55: 3537–3542

    PubMed  CAS  Google Scholar 

  34. Vatsis K.P., Weber W.W., Bell D.A., Dupret J.M., Evans D.A., Grant D.M., Hein D.W., Lin H.J., Meyer U.A., Relling M.V. and et al. (1995) Nomenclature for N-acetyltransferases. Pharmacogenetics 5: 1–17

    Article  PubMed  CAS  Google Scholar 

  35. Hein D.W., Doll M.A., Fretland A.J., Leff M.A., Webb S.J., Xiao G.H., Devanaboyina U.S., Nangju N.A. and Feng Y. (2000) Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer Epidemiol. Biomarkers Prev. 9: 29–42

    PubMed  CAS  Google Scholar 

  36. Lin H.J., Han C.Y., Lin B.K. and Hardy S. (1994) Ethnic distribution of slow acetylator mutations in the polymorphic N-acetyltransferase (NAT2) gene. Pharmacogenetics 4: 125–134

    Article  PubMed  CAS  Google Scholar 

  37. Cascorbi I., Drakoulis N., Brockmoller J., Maurer A., Sperling K. and Roots I. (1995) Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity. Am J Hum Genet 57: 581–592

    PubMed  CAS  Google Scholar 

  38. Paolo Vineis N.M., Matti Lang, Angelo d’Errico, Neil Caporaso, Jack Cuzick, Paolo Boffetta (eds.), Metabolic polymorphisms and susceptibility to cancer. IARC Sci. Publ. 148, International Agency for Research on Cancer, Lyon, 1999, pp. 159–195, 231–249, 251–270

  39. Breslow N.E. and Day N.E., Statistical methods in cancer research, vol I – The analysis of case–control studies, IARC Sci. Publ., 1980, pp. 5–338

  40. Tang R., Wang J.Y., Lo S.K. and Hsieh L.L. (1999) Physical activity, water intake and risk of colorectal cancer in Taiwan: a hospital-based case–control study. Int. J. Cancer 82: 484–489

    Article  PubMed  CAS  Google Scholar 

  41. Sivaraman L., Leatham M.P., Yee J., Wilkens L.R., Lau A.F. and Le Marchand L. (1994) CYP1A1 genetic polymorphisms and in situ colorectal cancer. Cancer Res. 54: 3692–3695

    PubMed  CAS  Google Scholar 

  42. Ishibe N., Stampfer M., Hunter D.J., Hennekens C. and Kelsey K.T. (2000) A prospective study of cytochrome P450 1A1 polymorphisms and colorectal cancer risk in men. Cancer Epidemiol. Biomark. Prev. 9: 855–856

    CAS  Google Scholar 

  43. Slattery M.L., Samowtiz W., Ma K., Murtaugh M., Sweeney C., Levin T.R. and Neuhausen S. (2004) CYP1A1, cigarette smoking, and colon and rectal cancer. Am. J. Epidemiol. 160: 842–852

    Article  PubMed  Google Scholar 

  44. Kiyohara C., Hirohata T. and Inutsuka S. (1996) The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene. Jpn. J. Cancer Res. 87: 18–24

    PubMed  CAS  Google Scholar 

  45. Nerurkar P.V., Okinaka L., Aoki C., Seifried A., Lum-Jones A., Wilkens L.R. and Le Marchand L. (2000) CYP1A1, GSTM1, and GSTP1 genetic polymorphisms and urinary 1-hydroxypyrene excretion in non-occupationally exposed individuals. Cancer Epidemiol. Biomark. Prev. 9: 1119–1122

    CAS  Google Scholar 

  46. Deakin M., Elder J., Hendrickse C., Peckham D., Baldwin D., Pantin C., Wild N., Leopard P., Bell D.A., Jones P., Duncan H., Brannigan K., Alldersea J., Fryer A.A. and Strange R.C. (1996) GlutathioneS-transferase GSTT1 genotyes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers. Carcinogenesis 17: 881–884

    Article  PubMed  CAS  Google Scholar 

  47. Zhong S., Wyllie A.H., Barnes D., Wolf C.R. and Spurr N.K. (1993) Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14: 1821–1824

    Article  PubMed  CAS  Google Scholar 

  48. Katoh T., Nagata N., Kuroda Y., Itoh H., Kawahara A., Kuroki N., Ookuma R. and Bell D.A. (1996) Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. Carcinogenesis 17: 1855–1859

    Article  PubMed  CAS  Google Scholar 

  49. Sgambato A., Campisi B., Zupa A., Bochicchio A., Romano G., Tartarone A., Galasso R., Traficante A. and Cittadini A. (2002) Glutathione S-transferase (GST) polymorphisms as risk factors for cancer in a highly homogeneous population from southern Italy. Anticancer Res. 22: 3647–3652

    PubMed  CAS  Google Scholar 

  50. Cotton S.C., Sharp L., Little J. and Brockton N. (2000) Glutathione S-transferase polymorphisms and colorectal cancer: a HuGE review. Am. J. Epidemiol. 151: 7–32

    PubMed  CAS  Google Scholar 

  51. Nijhoff W.A., Grubben M.J., Nagengast F.M., Jansen J.B., Verhagen H., van Poppel G. and Peters W.H. (1995) Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferases in humans. Carcinogenesis 16: 2125–2128

    Article  PubMed  CAS  Google Scholar 

  52. de Bruin W.C., Wagenmans M.J., Board P.G. and Peters W.H. (1999) Expression of glutathione S-transferase theta class isoenzymes in human colorectal and gastric cancers. Carcinogenesis 20: 1453–1457

    Article  PubMed  Google Scholar 

  53. Hung H.C., Chuang J., Chien Y.C., Chern H.D., Chiang C.P., Kuo Y.S., Hildesheim A. and Chen C.J. (1997) Genetic polymorphisms of CYP2E1, GSTM1, and GSTT1; environmental factors and risk of oral cancer. Cancer Epidemiol. Biomark. Prev. 6: 901–905

    CAS  Google Scholar 

  54. Sung P., Bailly V., Weber C., Thompson L.H., Prakash L. and Prakash S. (1997) Human xeroderma pigmentosum group D gene encodes a DNA helicase. Nature 365: 852–855

    Article  Google Scholar 

  55. Weeda G. and Hoeijmakers J.H. (1993) Genetic analysis of nucleotide excision repair in mammalian cells. Semin. Cancer Biol. 4: 105–117

    PubMed  CAS  Google Scholar 

  56. Tebbs R.S., Zhao Y., Tucker J.D., Scheerer J.B., Siciliano M.J., Hwang M., Liu N., Legerski R.J. and Thompson L.H. (1995) Correction of chromosomal instability and sensitivity to diverse mutagens by a cloned cDNA of the XRCC3 DNA repair gene. Proc. Natl. Acad. Sci. USA 92: 6354–6358

    Article  PubMed  CAS  Google Scholar 

  57. Park D.J., Stoehlmacher J., Zhang W., Tsao-Wei D.D., Groshen S. and Lenz H.J. (2001) A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. Cancer Res. 61: 8654–8658

    PubMed  CAS  Google Scholar 

  58. Palli D., Russo A., Masala G., Saieva C., Guarrera S., Carturan S., Munnia A., Matullo G. and Peluso M. (2001) DNA adduct levels and DNA repair polymorphisms in traffic-exposed workers and a general population sample. Int. J. Cancer 94: 121–127

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by Grant NSC 89-2314-B-002–373, NSC 90-2320-B-002-123 and NSC 91-2320-B-002-121 from the National Science Council and Grant DOH 85-HR-516, DOH 86-HR-516, and DOH 87-HR-516 from the National Health Research Institute, Department of Health, The Executive Yuan, Republic of China.

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  1. Department of Health Risk Management, College of Public Health, China Medical University, Taichung, 404, Taiwan, ROC

    Chih-Ching Yeh

  2. Institute of Environment Health, College of Public Health, China Medical University, Taichung, 404, Taiwan, ROC

    Fung-Chang Sung

  3. Colorectal Section, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC

    Reiping Tang & Chung Rong Chang-Chieh

  4. Department of Public Health, Chang Gung University, 259 Wen-Hwa 1 Road, Kwei-San, Tao-Yuan, 333, Taiwan, ROC

    Ling-Ling Hsieh

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  1. Chih-Ching Yeh
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Yeh, CC., Sung, FC., Tang, R. et al. Association between polymorphisms of biotransformation and DNA-repair genes and risk of colorectal cancer in Taiwan. J Biomed Sci 14, 183–193 (2007). https://doi.org/10.1007/s11373-006-9139-x

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