- Volume 14 Issue 9
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The Codon 399 Arg/Gln XRCC1 Polymorphism is Associated with Lung Cancer in Indians
- Natukula, Kirmani (Genetics Department, Bhagwan Mahavir Medical Research Centre) ;
- Jamil, Kaiser (Genetics Department, Bhagwan Mahavir Medical Research Centre) ;
- Pingali, Usha Rani (Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences) ;
- Attili, Venkata Satya Suresh (Department of Medical Oncology, BIBI General Hospitals and Cancer Centre) ;
- Madireddy, Umamaheshwar Rao Naidu (Central Research Institute of Unani Medicine)
- Published : 2013.09.30
Background: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair) pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene (at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility. Materials and Methods: We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed. Results: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%), and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Gln genotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenario where Arg399Gln genotypes were found to be associated with stage of the disease in females. Conclusions: It is concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients with smoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lung cancer for diagnosis and prognosis.
Non small cell lung cancer (NSCLC);x-ray repair cross complimenting group I (XRCC1)
- Chen S, Tang D, Xue K, et al (2002). DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a chinese population. Carcinogenesis, 23, 1321-5. https://doi.org/10.1093/carcin/23.8.1321
- De Ruyck K, Szaumkessel M, De Rudder I, et al (2007). Polymorphisms in base-excision repair and nucleotideexcision repair genes in relation to lung cancer risk. Mutat Res, 631, 101-10. https://doi.org/10.1016/j.mrgentox.2007.03.010
- Divine KK, Gilliland FD, Crowell RE, et al (2001). The XRCC1 399 Glutamine allele is a risk factor for adenocarcinoma of the lung. Mutat Res, 461, 273-8. https://doi.org/10.1016/S0921-8777(00)00059-8
- Doll R (1998). Uncovering the effects of smoking: historical perspective. Stat Methods Med Res, 7, 87-117. https://doi.org/10.1191/096228098668199908
- Gangwar R, Manchanda PK, Mittal RD (2009). Implications of XRCC1, XPD and APE1 gene polymorphism in North Indian population: a comparative approach in different ethnic groups worldwide. Genetica, 136, 163-9. https://doi.org/10.1007/s10709-008-9329-8
- Duell EJ, Millikan RC, Pittman GS, et al (2001). Polymorphism in the DNA repair gene XRCC1 and breast cancer. Cancer Epidemiol Biomarkers Prev, 10, 217-22.
- Engin AB, Karahalil B, Karakaya AE, et al (2011). Association between XRCC1 Arg399gln and p53 arg72pro polymorphisms and the risk of gastric and colorectal cancer in Turkish population. Arh Hig Rada Toksikol, 62, 207-14.
- Fard-Esfahani P, Fard-Esfahani A, Fayaz S, et al (2011). Association of Arg194Trp, Arg280His and Arg399Gln polymorphisms in x-ray repair cross-complementing group 1 gene and risk of differentiated thyroid carcinoma in Iran. Iranian Biomedical J, 15, 73-8.
- Guo S, Li X, Gao M, et al (2013). The Relationship between XRCC1 and XRCC3 gene polymorphisms and lung cancer risk in Northeastern Chinese. Plos One, 8, 1-5.
- Hoeijmakers JH (2001). Genome maintenance mechanisms for preventing cancer. Nature, 411, 366-74. https://doi.org/10.1038/35077232
- Hu XB, Feng Z, Fan YC, et al (2005). XRCC1 polymorphism and cancer risk: a meta analysis of 38 case-control studies. Cancer Epidemiol Biomarkers prev, 143, 1810-8.
- Hu XB, Feng Z, Fan YC, et al (2011). Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to glioma. Asian Pac J Cancer Prev, 12, 2981-4.
- Karkucak M, Yakut T, Evrensel T, et al (2012). XRCC1 gene polymorphisms and risk of lung cancer in Turkish patients. Int J Hum Genet, 12, 113-7. https://doi.org/10.1080/09723757.2012.11886171
- Kiran M, Saxena R, Kaur J (2010). Distribution of XRCC1 genotypes in north Indian population. Indian J Med Res, 131, 71-5.
- Mao Y, Xu X, Lin Y et al (2013). Quantitative assessment of the associations between XRCC1 polymorphisms and bladder cancer risk. World J Surg Oncol, 11, 58. https://doi.org/10.1186/1477-7819-11-58
- Kirmani N, Jamil K, Naidu MUR (2010). Occupational and environmental carcinogens in epidemiology of lung cancer in South Indian population. Biol Med, 2, 1-11.
- Knight RD, Parshad R, Price FM, et al (1993). X-ray-induced chromatid damage in relation to DNA repair and cancer incidence in family members. Int J Cancer, 54, 589-93. https://doi.org/10.1002/ijc.2910540412
- Kumar A, Pant MC, Singh HS, et al (2012). Associated risk of XRCC1 and XPD cross talk and life style factors in progression of head and neck cancer in north Indian population. Mut Res, 729, 24-34. https://doi.org/10.1016/j.mrfmmm.2011.09.001
- Miller SL, Dykes DD, Polesky HF (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nuc Acid Res, 16, 12-5.
- Misra RR, Ratnasinghe D, Tangrea JA, et al (2003). 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, 191, 171-8. https://doi.org/10.1016/S0304-3835(02)00638-9
- Mohrenweiser HW, Jones IM (1998). Variation in DNA repair is a factor in cancer susceptibility: a paradigm for the promises and perils of individual and population risk estimation? Mutat Res, 400, 15-24. https://doi.org/10.1016/S0027-5107(98)00059-1
- Nissar S, Lone TA, Banday MZ, et al (2013). Arg399Gln polymorphism of XRCC1 gene and risk of colorectal cancer in Kashmir: a case control study. Oncology Letters, 5, 959-63. https://doi.org/10.3892/ol.2013.1104
- Pachouri SS, Sobti RC, Kaur P, et al (2007). Constrasting impact of DNA repair gene XRCC1 polymorphism Arg399Gln and Arg 194 Trp on the risk of lung cancer in the north-Indian population. DNA Cell Biol, 26, 186-91. https://doi.org/10.1089/dna.2006.9999
- Sabitha K, Vishnuvardhan MR, Kaiser J (2009). Mutation in XRCC1 gene alters the genetic risks of Head and Neck cancer patients. Int J Cancer Research, 5, 58-68. https://doi.org/10.3923/ijcr.2009.58.68
- Park JY, Lee SY, Jeon HS, et al (2002). Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev, 11, 23-7.
- Ratnasinghe D, Yao SX, Tangrea JA, et al (2001). Polymorphism of the DNA repair gene XRCC1 and lung cancer risk. Cancer Epidemiol Biomarkers Prev, 10, 119-23.
- Ryk C, Kumar R, Thirumaran RK, et al (2006). Polymorphisms in the DNA repair genes XRCC1, APEX1, XRCC3 and NBS1, and the risk for lung cancer in never-and eversmokers. Lung Cancer, 54, 285-92. https://doi.org/10.1016/j.lungcan.2006.08.004
- Schneider J, Classen V, Bernges U, et al (2005). XRCC1 polymorphism and lung cancer risk in relation to tobacco smoking. Int J Mol Med, 16, 709-16.
- Schneider J, Classen V, Helmig S (2008). XRCC1 polymorphism and lung cancer risk. Expert Rev Mol Diagn, 8, 761-80. https://doi.org/10.1586/14737188.8.131.521
- Shen MR, Jones IM, Mohrenweiser H (1998). Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res, 58, 604-8.
- Spitz MR, Mc Pherson RS, Jiang HH, et al (1997). Correlates of mutagen sensitivity in patients with upper aerodigestive tract cancer. Cancer Epidemiol Biomark Prev, 6, 687-9.
- Sreeja L, Syamala VS, Syamala V, et al (2008). Prognostic importance of DNA repair gene polymorphisms of XRCC1 Arg399Gln and XPD Lys751Gln in lung cancer patients from India. J Cancer Res Clin Oncol, 134, 645-52. https://doi.org/10.1007/s00432-007-0328-4
- Thompson LH, Bachinski LL, Stallings RL, et al (1989). Complementation of repair gene mutations on the hemizygous chromosome 9 in CHO: a third repair gene on human chromosome 19. Genomics, 5, 670-9. https://doi.org/10.1016/0888-7543(89)90107-9
- Zhang X, Miao X, Liang G, et al (2005). Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. Cancer Res, 6, 722-6.
- Wei Q, Cheng L, Hong WK, et al (1996). Reduced DNA repair capacity in lung cancer patients. Cancer Res, 56, 4103-7.
- Yin J, Vogel U, Ma Y, et al (2007). The DNA repair gene XRCC1 and genetic susceptibility of lung cancer in northeastern Chainese population. Lung Cancer, 56, 153-60. https://doi.org/10.1016/j.lungcan.2006.12.012
- Yu Z, Chen J, Ford BN, et al (1999). Human DNA repair systems: an overview. Environ Mol Mutagen, 33, 3-20. https://doi.org/10.1002/(SICI)1098-2280(1999)33:1<3::AID-EM2>3.0.CO;2-L
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