Top

BMC Cancer

Published in:

Open Access 01-12-2005 | Research article

Polymorphisms of the XRCC1, XRCC3, & XPDgenes, and colorectal cancer risk: a case-control study in Taiwan

Authors: Chih-Ching Yeh, Fung-Chang Sung, Reiping Tang, Chung Rong Chang-Chieh, Ling-Ling Hsieh

Published in: BMC Cancer | Issue 1/2005

Abstract

Background

Recent studies relating to the association between DNA repair-gene polymorphisms and colorectal cancer risk would, to the best of our knowledge, appear to be very limited. This study was designed to examine the polymorphisms associated with three DNA repair genes, namely: XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, and investigate their role as susceptibility markers for colorectal cancer.

Methods

We conducted a case-control study including 727 cases of cancer and 736 hospital-based age- and sex-matched healthy controls to examine the role of genetic polymorphisms of three DNA-repair genes (XRCC1, XRCC3 and XPD) in the context of colorectal cancer risk for the Taiwanese population. Genomic DNA isolated from 10 ml whole blood was used to genotype XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis.

Results

The risk for colorectal cancer did not appear to differ significantly amongst individuals featuring the XRCC1 399Arg/Arg genotype (OR = 1.18; 95% CI, 0.96–1.45), the XRCC3 241Thr/Thr genotype (OR = 1.25; 95% CI, 0.88–1.79) or the XPD 751Gln allele (OR = 1.20; 95% CI, 0.90–1.61), although individuals featuring a greater number of risk genotypes (genotype with OR greater than 1) did experience a higher risk for colorectal cancer when compared to those who didn't feature any risk genotypes (Trend test P = 0.03). Compared with those individuals who didn't express any putative risk genotypes, individuals featuring all of the putative risk genotypes did experience a significantly greater cancer risk (OR = 2.43, 95% CI = 1.21–4.90), particularly for individuals suffering tumors located in the rectum (OR = 3.18, 95% CI = 1.29–7.82) and diagnosed prior to the age of 60 years (OR = 4.90, 95% CI = 1.72–14.0).

Conclusions

Our results suggest that DNA-repair pathways may simultaneously modulate the risk of colorectal cancer for the Taiwanese population, and, particularly for rectal cancer and younger patients.

Vineis P: Epidemiology of cancer from exposure to arylamines. Environ Health Perspect. 1994, 7-10. Suppl 6

Vineis P, Talaska G, Malaveille C, Bartsch H, Martone T, Sithisarankul P, Strickland P: DNA adducts in urothelial cells: relationship with biomarkers of exposure to arylamines and polycyclic aromatic hydrocarbons from tobacco smoke. Int J Cancer. 1996, 65: 314-316.CrossRefPubMed

Charames GS, Bapat B: Genomic instability and cancer. Curr Mol Med. 2003, 3: 589-596.CrossRefPubMed

Lunn RM, Langlois RG, Hsieh LL, Thompson CL, Bell DA: XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res. 1999, 59: 2557-2561.PubMed

Matullo G, Guarrera S, Carturan S, Peluso M, Malaveille C, Davico L, Piazza A, Vineis P: DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study. Int J Cancer. 2001, 92: 562-567. 10.1002/ijc.1228.CrossRefPubMed

Hou SM, Falt S, Angelini S, Yang K, Nyberg F, Lambert B, Hemminki K: The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis. 2002, 23: 599-603. 10.1093/carcin/23.4.599.CrossRefPubMed

Ankathil R, Jyothish B, Madhavan J, Nair MK: Deficient DNA repair capacity: a predisposing factor and high risk predictive marker in familial colorectal cancer. J Exp Clin Cancer Res. 1999, 18: 33-37.PubMed

Cheng L, Spitz MR, Hong WK, Wei Q: Reduced expression levels of nucleotide excision repair genes in lung cancer: a case-control analysis. Carcinogenesis. 2000, 21: 1527-1530. 10.1093/carcin/21.8.1527.CrossRefPubMed

Wei Q, Cheng L, Amos CI, Wang LE, Guo Z, Hong WK, Spitz MR: Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J Natl Cancer Inst. 2000, 92: 1764-1772. 10.1093/jnci/92.6.440.CrossRefPubMed

10.

Rajaee-Behbahani N, Schmezer P, Risch A, Rittgen W, Kayser KW, Dienemann H, Schulz V, Drings P, Thiel S, Bartsch H: Altered DNA repair capacity and bleomycin sensitivity as risk markers for non-small cell lung cancer. Int J Cancer. 2001, 95: 86-91. 10.1002/1097-0215(20010320)95:2<86::AID-IJC1015>3.0.CO;2-B.CrossRefPubMed

11.

Spitz MR, Wu X, Wang Y, Wang LE, Shete S, Amos CI, Guo Z, Lei L, Mohrenweiser H, Wei Q: Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res. 2001, 61: 1354-1357.PubMed

12.

Shen MR, Jones IM, Mohrenweiser H: Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res. 1998, 58: 604-608.PubMed

13.

Goode EL, Ulrich CM, Potter JD: Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2002, 11: 1513-1530.PubMed

14.

Sung P, Bailly V, Weber C, Thompson LH, Prakash L, Prakash S: Human xeroderma pigmentosum group D gene encodes a DNA helicase. Nature. 1993, 365: 852-855. 10.1038/365852a0.CrossRefPubMed

15.

Weeda G, Hoeijmakers JH: Genetic analysis of nucleotide excision repair in mammalian cells. Semin Cancer Biol. 1993, 4: 105-117.PubMed

16.

Qiao Y, Spitz MR, Shen H, Guo Z, Shete S, Hedayati M, Grossman L, Mohrenweiser H, Wei Q: Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes. Carcinogenesis. 2002, 23: 295-299. 10.1093/carcin/23.2.295.CrossRefPubMed

17.

Caldecott KW, Aoufouchi S, Johnson P, Shall S: XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular 'nick-sensor' in vitro. Nucleic Acids Res. 1996, 24: 4387-4394. 10.1093/nar/24.22.4387.CrossRefPubMedPubMedCentral

18.

Kubota Y, Nash RA, Klungland A, Schar P, Barnes DE, Lindahl T: Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. EMBO J. 1996, 15: 6662-6670.PubMedPubMedCentral

19.

Cappelli E, Taylor R, Cevasco M, Abbondandolo A, Caldecott K, Frosina G: Involvement of XRCC1 and DNA ligase III gene products in DNA base excision repair. J Biol Chem. 1997, 272: 23970-23975. 10.1074/jbc.272.38.23970.CrossRefPubMed

20.

Tebbs RS, Zhao Y, Tucker JD, Scheerer JB, Siciliano MJ, Hwang M, Liu N, Legerski RJ, Thompson LH: Correction of chromosomal instability and sensitivity to diverse mutagens by a cloned cDNA of the XRCC3 DNA repair gene. Proc Natl Acad Sci U S A. 1995, 92: 6354-6358.CrossRefPubMedPubMedCentral

21.

Abdel-Rahman SZ, Soliman AS, Bondy ML, Omar S, El-Badawy SA, Khaled HM, Seifeldin IA, Levin B: Inheritance of the 194Trp and the 399Gln variant alleles of the DNA repair gene XRCC1 are associated with increased risk of early-onset colorectal carcinoma in Egypt. Cancer Lett. 2000, 159: 79-86. 10.1016/S0304-3835(00)00537-1.CrossRefPubMed

22.

Mort R, Mo L, McEwan C, Melton DW: Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer. Br J Cancer. 2003, 89: 333-337. 10.1038/sj.bjc.6601061.CrossRefPubMedPubMedCentral

23.

Yeh CC, Hsieh LL, Tang R, Chang-Chieh CR, Sung FC: Risk factors for colorectal cancer in Taiwan: a hospital-based case-control study. J Formos Med Assoc. 2003, 102: 305-312.PubMed

24.

Matullo G, Palli D, Peluso M, Guarrera S, Carturan S, Celentano E, Krogh V, Munnia A, Tumino R, Polidoro S, Piazza A, Vineis P: XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis. 2001, 22: 1437-1445. 10.1093/carcin/22.9.1437.CrossRefPubMed

25.

Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, Sanford KK, Bell DA: XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis. 2000, 21: 551-555. 10.1093/carcin/21.4.551.CrossRefPubMed

26.

Breslow NE, Day NE: Statistical Methods in Cancer Research – The Analysis of Case-Control Studies. IARC scientific publications No. 32. 1980, Lyon: International Agency for Research on Cancer, 1:

27.

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

28.

Lee JM, Lee YC, Yang SY, Yang PW, Luh SP, Lee CJ, Chen CJ, Wu MT: Genetic polymorphisms of XRCC1 and risk of the esophageal cancer. Int J Cancer. 2001, 95: 240-246. 10.1002/1097-0215(20010720)95:4<240::AID-IJC1041>3.0.CO;2-1.CrossRefPubMed

29.

Wu HC, Liao KM, Hung PW, Weng TH, Yang PC, Chen CJ: Interactive effects of exposures to tobacco smoke and cooking fume and genetic polymorphisms of DNA repair enzymes on female lung adenocarcinoma in northern Taiwan. Taiwan J Public Health. 2001, 20: 357-364.

30.

Shen H, Wang X, Hu Z, Zhang Z, Xu Y, Hu X, Guo J, Wei Q: Polymorphisms of DNA repair gene XRCC3 Thr241Met and risk of gastric cancer in a Chinese population. Cancer Lett. 2004, 206: 51-58. 10.1016/j.canlet.2003.09.003.CrossRefPubMed

31.

Xing D, Qi J, Miao X, Lu W, Tan W, Lin D: Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population. Int J Cancer. 2002, 100: 600-605. 10.1002/ijc.10528.CrossRefPubMed

32.

Chen S, Tang D, Xue K, Xu L, Ma G, Hsu Y, Cho SS: DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. Carcinogenesis. 2002, 23: 1321-1325. 10.1093/carcin/23.8.1321.CrossRefPubMed

33.

Winsey SL, Haldar NA, Marsh HP, Bunce M, Marshall SE, Harris AL, Wojnarowska F, Welsh KI: A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer. Cancer Res. 2000, 60: 5612-5616.PubMed

34.

Smith TR, Miller MS, Lohman K, Lange EM, Case LD, Mohrenweiser HW, Hu JJ: Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer Lett. 2003, 190: 183-190. 10.1016/S0304-3835(02)00595-5.CrossRefPubMed

35.

Zhou W, Liu G, Miller DP, Thurston SW, Xu LL, Wain JC, Lynch TJ, Su L, Christiani DC: Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2003, 12: 359-365.PubMed

36.

Hu JJ, Smith TR, Miller MS, Mohrenweiser HW, Golden A, Case LD: Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis. 2001, 22: 917-922. 10.1093/carcin/22.6.917.CrossRefPubMed

37.

Dybdahl M, Vogel U, Frentz G, Wallin H, Nexo BA: Polymorphisms in the DNA repair gene XPD: correlations with risk and age at onset of basal cell carcinoma. Cancer Epidemiol Biomarkers Prev. 1999, 8: 77-81.PubMed

38.

Sturgis EM, Castillo EJ, Li L, Zheng R, Eicher SA, Clayman GL, Strom SS, Spitz MR, Wei Q: Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck. Carcinogenesis. 1999, 20: 2125-2129. 10.1093/carcin/20.11.2125.CrossRefPubMed

39.

Yu MW, Yang SY, Pan IJ, Lin CL, Liu CJ, Liaw YF, Lin SM, Chen PJ, Lee SD, Chen CJ: Polymorphisms in XRCC1 and glutathione S-transferase genes and hepatitis B-related hepatocellular carcinoma. J Natl Cancer Inst. 2003, 95: 1485-1488.CrossRefPubMed

40.

Divine KK, Gilliland FD, Crowell RE, Stidley CA, Bocklage TJ, Cook DL, Belinsky SA: The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung. Mutat Res. 2001, 461: 273-278.CrossRefPubMed

41.

Sturgis EM, Zheng R, Li L, Castillo EJ, Eicher SA, Chen M, Strom SS, Spitz MR, Wei Q: XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis. Carcinogenesis. 2000, 21: 2219-2223. 10.1093/carcin/21.12.2219.CrossRefPubMed

42.

Shen H, Xu Y, Qian Y, Yu R, Qin Y, Zhou L, Wang X, Spitz MR, Wei Q: Polymorphisms of the DNA repair gene XRCC1 and risk of gastric cancer in a Chinese population. Int J Cancer. 2000, 88: 601-606. 10.1002/1097-0215(20001115)88:4<601::AID-IJC13>3.0.CO;2-C.CrossRefPubMed

43.

Shen H, Sturgis EM, Dahlstrom KR, Zheng Y, Spitz MR, Wei Q: A variant of the DNA repair gene XRCC3 and risk of squamous cell carcinoma of the head and neck: a case-control analysis. Int J Cancer. 2002, 99: 869-872. 10.1002/ijc.10413.CrossRefPubMed

44.

Stern MC, Umbach DM, van Gils CH, Lunn RM, Taylor JA: DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk. Cancer Epidemiol Biomarkers Prev. 2001, 10: 125-131.PubMed

45.

Kuschel B, Auranen A, McBride S, Novik KL, Antoniou A, Lipscombe JM, Day NE, Easton DF, Ponder BA, Pharoah PD, Dunning A: Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet. 2002, 11: 1399-1407. 10.1093/hmg/11.12.1399.CrossRefPubMed

46.

Olshan AF, Watson MA, Weissler MC, Bell DA: XRCC1 polymorphisms and head and neck cancer. Cancer Lett. 2002, 178: 181-186. 10.1016/S0304-3835(01)00822-9.CrossRefPubMed

47.

Duell EJ, Wiencke JK, Cheng TJ, Varkonyi A, Zuo ZF, Ashok TD, Mark EJ, Wain JC, Christiani DC, Kelsey KT: Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis. 2000, 21: 965-971. 10.1093/carcin/21.5.965.CrossRefPubMed

48.

Hemminki K, Xu G, Angelini S, Snellman E, Jansen CT, Lambert B, Hou SM: XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis. 2001, 22: 1185-1188. 10.1093/carcin/22.8.1185.CrossRefPubMed

49.

Bufill JA: Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med. 1990, 113: 779-788.CrossRefPubMed

50.

Breivik J, Gaudernack G: Carcinogenesis and natural selection: a new perspective to the genetics and epigenetics of colorectal cancer. Adv Cancer Res. 1999, 76: 187-212.CrossRefPubMed

51.

Hong MY, Chapkin RS, Morris JS, Wang N, Carroll RJ, Turner ND, Chang WC, Davidson LA, Lupton JR: Anatomical site-specific response to DNA damage is related to later tumor development in the rat azoxymethane colon carcinogenesis model. Carcinogenesis. 2001, 22: 1831-1835. 10.1093/carcin/22.11.1831.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/5/12/prepub

Title: Polymorphisms of the XRCC1, XRCC3, & XPDgenes, and colorectal cancer risk: a case-control study in Taiwan
Authors: Chih-Ching Yeh
Fung-Chang Sung
Reiping Tang
Chung Rong Chang-Chieh
Ling-Ling Hsieh
Publication date: 01-12-2005
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2005
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-5-12

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2005

Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies

The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase

A molecular analysis by gene expression profiling reveals Bik/NBK overexpression in sporadic breast tumor samples of Mexican females

Short- and long-term cause-specific survival of patients with inflammatory breast cancer

Increased risk of cancer among relatives of patients with lung cancer in China

Differential biologic effects of CPD and 6-4PP UV-induced DNA damage on the induction of apoptosis and cell-cycle arrest

Keynote webinar | Spotlight on antibody–drug conjugates in cancer