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.
Similar content being viewed by others
References
Potter J.D. (1992) Reconciling the epidemiology, physiology, and molecular biology of colon cancer. JAMA 268: 1573–1577
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
Fearon E.R. and Vogelstein B. (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759–767
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
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
Houlston R.S. and Tomlinson I.P. (2001) Polymorphisms and colorectal tumor risk. Gastroenterology 121: 282–301
de Boer J.G. (2002) Polymorphisms in DNA repair and environmental interactions. Mutat. Res. 509: 201–210
Gertig D.M. and Hunter D.J. (1998) Genes and environment in the etiology sof colorectal cancer. Semin. Cancer Biol. 8: 285–298
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
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
Kiyohara C. (2000) Genetic polymorphism of enzymes involved in xenobiotic metabolism and the risk of colorectal cancer. J. Epidemiol. 10: 349–360
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
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
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
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
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
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
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
Braithwaite E., Wu X. and Wang Z. (1999) Repair of DNA lesions: mechanisms and relative repair efficiencies. Mutat. Res. 424: 207–219
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
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
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
Butler W.J., Ryan P. and Roberts-Thomson I.C. (2001) Metabolic genotypes and risk for colorectal cancer. J. Gastroenterol. Hepatol. 16: 631–635
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Weeda G. and Hoeijmakers J.H. (1993) Genetic analysis of nucleotide excision repair in mammalian cells. Semin. Cancer Biol. 4: 105–117
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
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
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
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11373-006-9139-x