Abstract
Background
DNA damage by endogenous or exogenous source of reactive oxygen species (ROS) plays an important role in induction and progression of various cancers. Physiologically, gallbladder is likely to be exposed to various ROS which leads to extensive DNA damage. Cells overcome the DNA damage by repair mechanisms. Genetic variants of OGG1 and XRCC1, important enzymes participating in base excision repair pathway, may confer interindividual variations in susceptibility to gallbladder cancer (GBC). This study was aimed to examine the role of OGG1 Ser326Cys (rs1052133) and XRCC1 Arg194Trp (C > T) (rs25487) and Arg399Gln (G > A) (rs1799782) polymorphisms in GBC susceptibility.
Methods
The study included 173 GBC patients and 204 controls. Genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Differences in the frequencies were estimated by chi-square test and risk was estimated by using unconditional logistic regression after adjusting for age and gender.
Results
OGG1Cys/Cys genotype frequency was significantly higher in GBC patients [odds ratio (OR) = 2.93; 95% confidence interval (CI) = 1.14–7.51]. The increased risk was more pronounced in female GBC patients (OR = 5.92; 95%CI = 1.20–29.13), patients with gallstone (OR = 5.50; 95%CI = 1.99–15.16), female gender, and late onset of disease (OR = 4.72, 95%CI = 1.43–15.53).
In XRCC1 Arg399Gln polymorphism, significant differences in frequencies of Gln/Gln and Arg/Gln genotypes conferred significantly low risk for GBC (OR = 0.62; 95%CI = 0.39–0.97 and OR = 0.37; 95%CI = 0.19–0.71 respectively).
However, XRCC1 Arg194Trp polymorphism was not associated with GBC. The carriers of Arg-Gln haplotype consisting of 194Arg and 399Gln alleles of XRCC1 were also at significant low risk for GBC (OR = 0.59, 95%CI = 0.42–0.82). Interaction of genotypes and tobacco usage did not modulate the risk.
Conclusion
Results suggest that Cys/Cys genotype of OGG1 Ser326Cys polymorphism is associated with increased risk of GBC. However, Arg399Gln polymorphism and Arg-Gln haplotype comprising XRCC1 Arg194Trp and Arg399Gln polymorphisms conferred low risk for GBC susceptibility.
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References
Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: Geographical distribution and risk factors. Int J Cancer. 2006;118:1591–1602.
Coleman MP, Esteve J, Damiecki P, Arslan A, Renard H. Trends in cancer incidence and mortality, Lyon, IARC 1993.
Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumor. Nat Rev Cancer. 2004;4:695–706.
Lazcano-Ponce EC, Miquel JF, Munoz N. Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin. 2001;51:349–64.
Takahashi T, Shivapurkar N, Riquelme E. Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis. Clin Cancer Res. 2004;10:6126–33.
Chatterjee A, Mambo E, Zhang Y, De Weese T, Sidransky D. Targeting of mutant hogg1 in mammalian mitochondria and nucleus: effect on cellular survival upon oxidative stress. BMC Cancer. 2006;6:235.
Sakamoto T, Higaki Y, Hara M, Ichiba M, Horita M, Mizuta T, et al. Ser326Cys Polymorphism and risk of hepatocellular carcinoma among Japanese. J Epidemiol. 2006;16:233–9.
Elahi A, Zheng Z, Park J, Eyring K, McCaffrey T, Lazarus P. The human OGG1 DNA repair enzyme and its association with orolaryngeal cancer risk. Carcinogenesis. 2002;23:1229–34.
Speina E, Arczewska KD, Gackowski D, Zieli ń ska M, Siomek A, Kowalewski J, et al. Contribution of hMTH1 to the maintenance of 8-oxoguanine levels in lung DNA of non-small-cell lung cancer patients. J Natl Cancer Inst. 2005;97:384–95.
Bravard A, Vacher M, Gouget B, Coutant A, Hillairet de Boisferon F, Marsin S, et al. Redox regulation of human OGG1 activity in response to cellular oxidative stress. Mol Cell Biol. 2006;26:7430–6.
Nyaga SG, Lohani A, Jaruga P, Trzeciak AR, Dizdaroglu M, Evans MK. Reduced repair of 8-hydroxyguanine in the human breast cancer cell line, HCC1937. BMC Cancer. 2006;6:297.
Ide H, Kotera M. Human DNA Glycosylases involved in the repair of oxidatively damaged DNA. Biol Pharm Bull. 2004;27:480–5.
Zhang H, Mizumachi T, Carcel-Trullols J, Li L, Naito A, Spencer HJ, et al. Targeting human 8-oxoguanine DNA glycosylase (hOGG1) to mitochondria enhances cisplatin cytotoxicity in hepatoma cells. Carcinogenesis. 2007;28:1629–37.
Park HW, Kim IJ, Kang HC, Jang SG, Ahn SA, Lee JS, et al. The hOGG1 Ser326Cys polymorphism is not associated with colorectal cancer. Risk J Epidemiol. 2007;17:156–60.
Jiao X, Huang J, Wu S, Lv M, Hu Y, Jianfu, et al. hOGG1 Ser326Cys polymorphism and susceptibility to gallbladder cancer in a Chinese population. Int J Cancer. 2007;121:501–5.
Han J, Hankinson SE, De Vivo I, Spiegelman D, Tamimi RM, Mohrenweiser HW, et al. A prospective study of XRCC1 haplotypes and their interaction with plasma carotenoids on breast cancer risk. Cancer Res. 2003;63:8536–41.
Chang-Claude J, Popanda O, Tan XL, Kropp S, Helmbold I, von Fournier D, et al. Associations between polymorphisms in the DNA repair genes, XRCC1, APE1, and XPD and acute side effects of radiotherapy in breast cancer patients. Clin Cancer Res. 2005;11:4802–9.
Jennifer JH, Tasha RS, Mark SM, Harvey WM, Andrea G, Douglas Case L. Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis. 2001;22:917–22.
Bearhs O, Henson D, Hutter R (1988) Manual for staging of cancer. Philadelphia: Lippincott; 1988.
Miller SA, Dykes DD, Polesky HF. A salting procedure for extracting DNA from nucleated cells. Nucl Acid Res. 1988;16:1215.
Ramachandran S, Ramadas K, Hariharan R, Kumar RR, Pillai MR. Single nucleotide polymorphisms of DNA repair genes XRCC1 and XPD and its molecular mapping in Indian oral cancer. Oral Oncol. 2006;42:350–62.
Loïc Le M, Timothy D, Annette LJ, Ann S, Lynne R. Association of the hOGG1 Ser326Cys polymorphism with lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11:409–12.
Kohno T, Kunitoh H, Toyama K, Yamamoto S, Kuchiba A, Saito D, et al. Association of the OGG1-Ser326Cys polymorphism with lung adenocarcinoma risk. Cancer Sci. 2006;97:724–8.
Shen J, Deininger P, Hunt JD, Zhao H. 8-Hydroxy–20-deoxyguanosine (8-OH-dG) as a potential survival biomarker in patients with nonsmall-cell lung cancer. Cancer. 2007;109:574–80.
Luna L, Rolseth V, Hildrestrand GA, Otterlei M, Dantzer F, Bjørås M, et al. Dynamic relocalization of hOGG1 during the cell cycle is disrupted in cells harboring the hOGG1-Cys326 polymorphic variant. Nucl Acids Res. 2005;33:1813–24.
Sugimura H, Kohno T, Wakai K. hOGG1 Ser326Cys polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev. 1999;8:669–74.
Marchand L Le, Donlon T, Lum-Jones A, Seifried A, Wilkens LR. Association of the hOGG1 Ser326Cys polymorphism with lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11:409–12.
Xing DY, Tan W, Song N, Lin DX. Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese population. Int J Cancer. 2001;95:140–3.
Sheehan AM, McGregor DK, Patel A, Shidham V, Fan CY, Chang CC. Expression of human 8-oxoguanine DNA glycosylase (hOGG1) in follicular lymphoma. Mod Pathol. 2006;18:1512–8.
Shen M, Hung RJ, Brennan P, Malaveille C, Donato F, Placidi D, 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 Biomark Prev. 2003;12:1234–40.
Duell EJ, Wiencke JW, Cheng TJ, Varkonyi A, Zuo ZF, Ashok TDS. Polymorphisms in the DNA repair genes XRCC1and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis. 2000;21:965–71.
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;22:917–22.
Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomark Prev. 2002;11:1513–30.
Huang WY, Gao YT, Rashid A, Sakoda LC, Deng J, Shen MC, et al. Selected base excision repair gene polymorphisms and susceptibility to biliary tract cancer and biliary stones: a population-based case-control study in China. Carcinogenesis. 2008;29:100–5.
Park JY, Lee SY, Jeon HS, Bae NC, Chae SC, Joo S, et al. Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer. Cancer Epidemiol Biomark Prev. 2002;11:23–7.
Zhou W, Liu G, Miller DP, Thurston SW, Xu LL, Wain JC, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. Cancer Epidemiol Biomark Prev. 2003;12:359–65.
Sturgis EM, Castillo EJ, Li L, Zheng R, Eicher SA, Clayman GL, et al. Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck. Carcinogenesis. 1999;20:2125–9.
Shu XO, Cai Q, Gao YT, Wen W, Jin F, Zheng W. A Population-based case-control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. Cancer Epidemiol Biomark Prev. 2003;12:1462–7.
Stern MC, Umbachvan DM, Gils CH, Lunn RM, Taylor JA. DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk. Cancer Epidemiol. Biomark Prev. 2001;10:125–31.
Nelson HH, Kelsey KT, Mott LA, Karagas MR. The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene–environment interaction. Cancer Res. 2002;62:152–5.
Misra RR, Ratnasinghe D, Tangrea JA, Virtamo J, Andersen MR, Barrett M, et al. Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref–1, and the risk of lung cancer among male smokers in Finland. Cancer Lett. 2003;191:171–8.
Matullo G, Guarrera S, Carturan S, Peluso M, Malaveille C, Davico L, et al. DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study. Int J Cancer. 2001;92:562–7.
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The study was supported by research and fellowship grants from Indian Council of Medical Research and Department of Science and Technology, Govt. of India.
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Srivastava, A., Srivastava, K., Pandey, S.N. et al. Single-Nucleotide Polymorphisms of DNA Repair Genes OGG1 and XRCC1: Association with Gallbladder Cancer in North Indian Population. Ann Surg Oncol 16, 1695–1703 (2009). https://doi.org/10.1245/s10434-009-0354-3
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DOI: https://doi.org/10.1245/s10434-009-0354-3