- Volume 15 Issue 23
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Association of RAD 51 135 G/C, 172 G/T and XRCC3 Thr241Met Gene Polymorphisms with Increased Risk of Head and Neck Cancer
- Kayani, Mahmood Akhtar (Department of Biosciences, COMSATS Institute of Information and Technology) ;
- Khan, Sumeera (Department of Biosciences, COMSATS Institute of Information and Technology) ;
- Baig, Ruqia Mehmood (Department of Zoology, Pir Mehr Ali Shah University of Arid Agriculture University) ;
- Mahjabeen, Ishrat (Department of Biosciences, COMSATS Institute of Information and Technology)
- Published : 2015.01.06
Homologous recombination repair (HRR) plays an important role in protection against carcinogenic factors. Genes regulating the HRR mechanisms may impair their functions and consequently result in increased cancer susceptibility. RAD 51 and XRCC3 are key regulators of the HRR pathway and genetic variability in these may contribute to the appearance and progression of various cancers including head and neck cancer (HNC). The aim of the present study was to compare the distribution of genotypes of RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms between HNC patients and controls. Each polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) technique in 200 pathologically confirmed HNC patients along with 150 blood samples from normal, disease free healthy individuals. We observed that homozygous variant CC genotype of RAD51 135G/C was associated with a 2.5 fold increased HNC risk (OR=2.5; 95%CI=0.69-9.53; p<0.02), while second polymorphism of RAD 51 172 G/T, heterozygous variant GT genotype was associated with a 1.68 fold (OR=1.68; 95%CI=1.08-2.61; p<0.02) elevation when compared with controls. In the case of the Thr241Met polymorphism of XRCC3, we observed a 16 fold (OR=16; 95% CI=3.78-69.67; p<0.0002) increased HNC risk in patients compared to controls. These results further suggested that RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms may be effective biomarkers for genetic susceptibility to HNC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.
HRR pathway;DSBs;RAD 51 polymorphism;XRCC3 polymorphism;HNC;smoking status
- Bray F, Ren JS, Masuyer E, Ferlay J (2012). Estimates of global cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer, 132, 1133-45.
- Areeshi MY (2013). Genetic variation in a DNA double strand break repair gene in saudi population: a comparative study with worldwide ethnic groups. Asian Pac J Cancer Prev, 14, 7091-4. https://doi.org/10.7314/APJCP.2013.14.12.7091
- Auranen A, Song H, Waterfall C, et al (2005). Polymorphisms in DNA repair genes and epithelial ovarian cancer risk. Int J Cancer, 117, 611-8. https://doi.org/10.1002/ijc.21047
- Cheng D, Shi H, Zhang K, Yi L, Zhen G (2014). RAD51 Gene 135G/C polymorphism and the risk of four types of common cancers: a meta-analysis. Diagn Pathol, 23, 9-18.
- Fayaz S, Karimmirza M, Tanhaei S, et al (2013). Increased risk of differentiated thyroid carcinoma with combined effects of homologous recombination repair gene polymorphisms in an Iranian population. Asian Pac J Cancer Prev, 14, 6727-31. https://doi.org/10.7314/APJCP.2013.14.11.6727
- Hasselbach L, Haase S, Fischer D, Kolberg HC, Sturzbecher HW (2005). Characterisation of the promoter region of the human DNA-repair gene Rad51. Eur J Gynaecol Oncol, 26, 589-98.
- Krupta R, Slinwinski T, Wisniewska-Jarosinska M et al (2011). Polymorphisms in RAD51, XRCC2 and XRCC3 genes of the homologous recombination repair in colorectal cancer-a case control study. Mol Biol Rep, 38, 2849-54. https://doi.org/10.1007/s11033-010-0430-6
- Lee KM, Choi JY, Kang C, et al (2005). Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk. Clin Cancer Res, 11, 4620-6. https://doi.org/10.1158/1078-0432.CCR-04-2534
- Liang HJ, Yan YL, Liu ZM, et al (2013). Association of XRCC3 Thr241Met polymorphisms and glioma risk: evidence from a meta-analysis. Asian Pac J Cancer Prev, 14, 4243-7. https://doi.org/10.7314/APJCP.2013.14.7.4243
- Lu J, Wang LE, Xiong P, et al (2007). 172G.T variant in the 59 untranslated region of DNA repair gene RAD51 reduces risk of squamous cell carcinoma of the head and neck and interacts with a P53 codon 72 variant. Carcinogenesis, 28, 988-94.
- Mahjabeen I, Baig RM, Masood N, et al (2011). OGG1 gene sequence variation in head and neck cancer patients in Pakistan. Asian Pac J Cancer Prev, 12, 2779-83.
- Mao CF, Qian WY, Wu JZ, Sun DW, Tang JH (2014). Association between the XRCC3 Thr241Met Polymorphism and Breast Cancer Risk: an Updated Meta-analysis of36 Case-control Studies. Asian Pac J Cancer Prev, 15, 6613-8. https://doi.org/10.7314/APJCP.2014.15.16.6613
- Matullo G, Domenico P, Marco P (2001). XRCC1, XRCC3, XPD gene polymorphisms, smoking and 32P-DNA adducts in a sample of healthy subjects. Carcinogenesis, 22, 1437-45. https://doi.org/10.1093/carcin/22.9.1437
- Michalska MM, Samulak D, Romanowicz H, Smolarz B (2014). Association of polymorphisms in the 5' untranslated region of RAD51 gene with risk ofendometrial cancer in the Polish population. Arch Gynecol Obstet. 2014 Jun 15
- Mimitou EP (2009). Nucleases and helicases take center stage in homologous recombination. Trends Biochem Sci, 34, 264-72. https://doi.org/10.1016/j.tibs.2009.01.010
- Moynahan ME, Jasin M (2010). Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol, 11, 196-207. https://doi.org/10.1038/nrm2851
- Mucha B, Przybylowska-Sygut K, Dziki L et al (2012). Lack of association between the 135G/C RAD51 gene polymorphism and the risk of colorectal cancer among Polish population. Pol Przegl Chir, 84, 358-62.
- Romanowicz-Makowska H, Smolarz B, Zadrozny M, et al (2012). The association between polymorphisms of the RAD51-G135C, XRCC2- Arg188His and XRCC3-Thr241Met genes and clinico-pathologic features in breast cancer in Poland. Eur J Gynaeco Oncol, 33, 145-50.
- Sabir M, Baig RM, Mahjabeen I, Kayani MA (2012). Novel germline CDK4 mutations in patients with head and neck cancer. Hered Cancer Clin Pract, 29, 10-11.
- Shin A, Lee KM, Ahn B, et al (2008). Genophenotype relationship between DNA repair gene genetic polymorphisms and DNA repair capacity. Asian Pac J Cancer Prev, 9, 501-5
- Siegel R, Ward E, Brawley O, Jemal A (2011). Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61, 212-36. https://doi.org/10.3322/caac.20121
- Tian X, Tian Y, Ma P, et al (2013). Association between the XRCC3 C241T polymorphism and lung cancer risk in the Asian population. Tumor Biol, 34, 2589-97. https://doi.org/10.1007/s13277-013-0806-z
- Venkitaraman AR (2009). Linking the cellular functions of BRCA genes to cancer pathogenesis and treatment. Annu Rev Pathol, 4, 461-87. https://doi.org/10.1146/annurev.pathol.3.121806.151422
- Vral A, Willems P, Claes K, et al (2011). Combined effect of polymorphisms in Rad51 and Xrcc3 on breast cancer risk and chro mosomal radiosensitivity. Mol Med Rep, 4, 901-12.
- Wang W, Li JL, He XF, et al (2013). Association between the RAD51 135 G>C polymorphism and risk of cancer: a meta-analysis of 19,068 cases and 22,630 controls. PLoS One, 9, 75153.
- Wang WW, Spurdle AB, Kolachana P, et al (2001). A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers. Cancer Epidemiol Biomark Prev, 10, 955-60.
- Wang Y, Liang D, Spitz MR, et al (2003). XRCC3 genetic polymorphism, smoking, and lung carcinoma risk in minority populations. Cancer, 15, 1701-6.
- Yin QH, Liu C, Li L, Zu XY, Wang YJ (2012). Association between the XRCC3 T241M polymorphism and head and neck cancer susceptibility: a meta-analysis of case-control studies. Asian Pac J Cancer Prev, 13, 5201-5. https://doi.org/10.7314/APJCP.2012.13.10.5201
- Zhang SX, Yang S, Xu CQ, et al (2014). Equivocal association of RAD51 polymorphisms with risk of esophageal squamous cell carcinoma in a Chinese population. Asian Pac J Cancer Prev, 15, 763-7. https://doi.org/10.7314/APJCP.2014.15.2.763
- Zhao M, Chen P, Dong Y, Zhu X, Zhang X (2014). Relationship between Rad51 G135C and G172T variants and the susceptibility to cancer: a meta-analysisinvolving 54 casecontrol studies. PLoS One, 27, 9, 87259. https://doi.org/10.1371/journal.pone.0087259
- Zhao Y, Deng X, Wang Z, Wang Q, Liu Y (2012). Genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 and risk of colorectal cancer in Chinese population. Asian Pac J Cancer Prev, 13, 665-9. https://doi.org/10.7314/APJCP.2012.13.2.665
- Zhou GW, Hu J, Peng XD, Li Q (2011). RAD51 135G>C polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat, 125, 529-35. https://doi.org/10.1007/s10549-010-1031-8
- Association of the CCDC26 rs4295627 polymorphism with the risk of glioma: Evidence from 7,290 cases and 11,630 controls vol.4, pp.5, 2016, https://doi.org/10.3892/mco.2016.813
- Association of DNA repair genes polymorphisms and mutations with increased risk of head and neck cancer: a review vol.34, pp.12, 2017, https://doi.org/10.1007/s12032-017-1057-4
- Increased Expression of ERCC2 Gene in Head and Neck Cancer is Associated with Aggressive Tumors: A Systematic Review and Case-Control Study vol.31, pp.1, 2016, https://doi.org/10.5301/jbm.5000186
- Association between RAD51 135 G/C polymorphism and risk of 3 common gynecological cancers vol.97, pp.26, 2018, https://doi.org/10.1097/MD.0000000000011251
- Polymorphism of DNA Repair Genes via Homologous Recombination (HR) in Ovarian Cancer pp.1532-2807, 2019, https://doi.org/10.1007/s12253-019-00604-5