XRCC1 Arg194Trp polymorphism and risk of chronic obstructive pulmonary disease

Abstract

The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease (COPD). However, just 20%–30% smokers develop COPD, which suggests that different degrees of DNA repair cause different outcomes in smokers. X-ray repair cross-complementing group 1 (XRCC1), a base excision repair protein, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks. The present study investigated the association between polymorphism in XRCC1 (Arg399Gln) and susceptibility of COPD. A total of 201 COPD cases and 309 controls were recruited and frequency-matched on age and sex. XRCC1 genotype was determined by PCR-restriction fragment length polymorphism analysis. Overall, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD had no significant difference among individuals with Trp/Trp genotype. However, after stratifying by smoking status, in former smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Trp/Trp genotype (adjusted OR=0.22, 95% CI 0.06–0.85, P=0.028); after stratifying by smoking exposure, in light smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Arg/Trp genotype and Trp/Trp genotype (adjusted OR=0.39, 95% CI 0.16–0.94, P=0.036; 0.24, 95% CI 0.07–0.79, P=0.019, respectively). In conclusion, XRCC1 Arg194Trp genotype is associated with a reduced risk of developing COPD among former and light smokers.

Keywords

chronic obstructive pulmonary disease / cigarette smoking / DNA damage / X-ray repair cross-complementing group 1

References

[1] PauwelsR.A., BuistA.S., CalverleyP.M., et al.. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med, 2001, 163(5): 256-276

[2] FishmanA.P.. One hundred years of COPD. Am J Respir Crit Care Med, 2005, 171(9): 941-948

[3] ManninoD.M., HomaD.M., AkinbamiL.J., et al.. Chronic obstructive pulmonary disease surveillance—United States, 1971–2000. MMWR Surveill Summ, 2002, 51(6): 1-16

[4] LokkeA., LangeP., ScharlingH., et al.. Developing COPD: a 25 year follow-up study of the general population. Thorax, 2006, 61(11): 935-939

[5] SandfordA.J., PareP.D.. Genetic risk factors for chronic obstructive pulmonary disease. Clin Chest Med, 2000, 21(4): 633-643

[6] PryorW.A.. Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environ Health Perspect, 1997, 105(Suppl4): 875-882

[7] ColemanC.N., HarrisJ.R.. Current scientific issues related to clinical radiation oncology. Radiat Res, 1998, 150(2): 125-133

[8] Vayssier-TaussatM., CamilliT., AronY., et al.. Effects of tobacco smoke and benzo[a]pyrene on human endothelial cell and monocyte stress responses. Am J Physiol Heart Circ Physiol, 2001, 280(3): H1293-H1300

[9] LindahlT., WoodR.D.. Quality control by DNA repair. Science, 1999, 286(5446): 1897-1905

[10] WangY., SpitzM.R., ZhuY., et al.. From genotype to phenotype: correlating XRCC1 polymorphisms with mutagen sensitivity. DNA Repair (Amst), 2003, 2(8): 901-908

[11] David-BeabesG.L., LondonS.J.. Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians. Lung Cancer, 2001, 34(3): 333-339

[12] BarberaJ.A., Peces-BarbaG., AgustiA.G., et al.. Clinical guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease. Arch Bronconeumol, 2001, 37(6): 297-316

[13] ShenM., HungR.J., BrennanP., et al.. Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case-control study in northern Italy. Cancer Epidemiol Biomarkers Prev, 2003, 12(11Pt1): 1234-1240

[14] BerwickM., VineisP.. Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst, 2000, 92(11): 874-897

[15] ShenM.R., JonesI.M., MohrenweiserH.. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res, 1998, 58(4): 604-608

[16] CaldecottK.W.. XRCC1 and DNA strand break repair. DNA Repair (Amst), 2003, 2(9): 955-969

[17] CalikogluM., AmerL., tes ArasN., et al.. The association between polymorphic genotypes of glutathione S-transferases and COPD in the Turkish population. Biochem Genet, 2006, 44(7–8): 307-319

[18] HungR.J., HallJ., BrennanP., et al.. Genetic polymorphisms in the base excision repair pathway and cancer risk: a huge review. Am J Epidemiol, 2005, 162(10): 925-942

[19] VodickaP., StetinaR., PolakovaV., et al.. Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects. Carcinogenesis, 2007, 28(3): 657-664

[20] ThompsonL.H., WestM.G.. XRCC1 keeps DNA from getting stranded. Mutat Res, 2000, 459(1): 1-18

[21] CaoY., MiaoX.P., HuangM.Y., et al.. Polymorphisms of XRCC1 genes and risk of nasopharyngeal carcinoma in the Cantonese population. BMC Cancer, 2006, 6: 167

[22] HortonJ.K., WatsonM., StefanickD.F., et al.. XRCC1 and DNA polymerase beta in cellular protection against cytotoxic DNA single-strand breaks. Cell Res, 2008, 18(1): 48-63

[23] Abdel-RahmanS.Z., El-ZeinR.A.. The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by the tobacco-specific nitrosamine NNK. Cancer Lett, 2000, 159(1): 63-71

[24] LunnR.M., LangloisR.G., HsiehL.L., et al.. XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res, 1999, 59(11): 2557-2561

[25] XanthoudakisS., MiaoG., WangF., et al.. Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. Embo J, 1992, 11(9): 3323-3335

[26] KelleyM.R., ChengL., FosterR., et al.. Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer. Clin Cancer Res, 2001, 7(4): 824-830