Examination of RAD51 gene G135C polymorphism in gastric cancer patients in northeastern Anatolia
Keywords:gastric cancer, RAD51 gene, genetic polymorphism, RFLP, DNA repair
- Gastric cancer is the third most common cause of cancer mortality, with cancer incidence varying among populations. RAD51 is a DNA repair gene associated with different cancer types in different populations.
- G135C polymorphism of the RAD51 gene among gastric cancer patients and healthy individuals was genotyped to test the association between gene polymorphism and cancer prevalence in the northeastern Anatolian population for the first time.
- Both genotypic and allelic frequencies of the polymorphism differed significantly between heathy and gastric cancer patients, implying an association between the C allele in the RAD51 gene and gastric cancer.
Abstract: Polymorphisms of DNA repair and genome integrity genes are associated with DNA repair capacity and elevated cancer risk. To establish an association between the pattern of polymorphism and the incidence of any type of cancer, studies across different populations are required. Polymorphic regions have been identified in the RAD51 repair gene in various cancer types; however, the influence of specific genetic variants on gastric cancer prevalence has not been empirically demonstrated. We conducted a case-control study with 76 gastric cancer patients and 78 healthy individuals from northeastern Anatolia to examine the association between polymorphism and gastric cancer. We genotyped the previously identified G135C polymorphism of RAD51 in all individuals and estimated the allele and genotype frequencies in the two groups. Our results indicated that the two groups differed both in allele and genotype frequencies. Additionally, a significant and elevated odd ratio (3.53) of gastric cancer for the C allele of RAD51 was observed. The genotypes GC and CC had also significant and high odd ratios (>3.75). Our results indicate that G135C polymorphism of the RAD51 gene was associated with an increased risk of gastric cancer in the examined population.
Received: November 21, 2018; Revised: December 25, 2018; Accepted: January 18, 2019; Published online: January 23, 2019
How to cite this article: Gok I, Ozden O. Examination of RAD51 gene G135C polymorphism in gastric cancer patients in northeastern Anatolia. Arch Biol Sci. 2019;71(2):209-13.
Lindsey A, Torre M , Freddie B, Siegel R, Ferlay J, Tieulent JL, Jemal A. Global Cancer Statistics 2015. Cancer J Clin. 2015;65:87-108.
Cheng D, Shi H, Zhang K, Yi L, Zhen G. RAD51 Gene 135G/C polymorphism and the risk of four types of common cancers: a meta-analysis. Diagn Pathol. 2014;23:9-18.
Romanowicz-Makowska H, Samulak D, Michalska M, Sporny S, Langner E, Dziki A, Sychowski R, Smolarz B.RAD51 gene polymorphisms and sporadic colorectal cancer risk in Poland. Pol J Pathol. 2012;63(3):193-8.
Pal J, Bertheau R, Buon L, Qazi A, Batchu RB, Bandyopadhyay S, Ali-Fehmi R, Beer DG, Weaver DW, Shmookler Reis RJ, Goyal RK, Huang Q, Munshi NC, Shammas MA. Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome. Oncogene. 2011;18:30(33):3585-98.
Wiśniewska-Jarosińska M, Sliwińfski T, Krupa R, Stec-Michalska K, Chojnacki J, Błasiak J. The role of RAD 51 gene polymorphism in patients with colorectal cancer in the Polish subpopulation. Pol Merkur Lekarski. 2009;2(155):455-7.
Poplawski T, Arabski M, Kozirowska D, Blasinska-Morawiec M, Morawiec Z, Morawiec-Bajda A, Klupińska G, Jeziorski A, Chojnacki J, Blasiak J. DNA damage and repair in gastric cancer a correlation with the hOGG1 and RAD51 genes polymorphisms. Mutat Res. 2006;10;601(1-2):83-91.
Richardson C. RAD51, genomic stability, and tumorigenesis. Cancer Lett. 2005;218:127-39.
West SC. Molecular views of recombination proteins and their control. Nat Rev Mol Cell Biol. 2003;4:435-45.
Nissar S, Baba, SM, Akhtar T, Rasool R, Shah Z A, Sameer AS. RAD51 G135C gene polymorphism and risk of colorectal cancer in Kashmir. Eur J Cancer Prevn. 2014;23(4):264-268.
Wang WW, Spurdle AB, Kolachana P, Bove B, Modan B, Ebbers SM, Suthers G, Tucker MA, Kaufman DJ, Doody MM, Tarone RE, Daly M, Levavi H, Pierce H, Chetrit A, Yechezkel GH, Chenevix-Trench G, Offit K, Godwin AK, Struewing JP. A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers. Cancer Epidemiol Biomarkers Prev. 2001;10:955-60.
Krupa R, Sliwinski T, Wisniewska-Jarosinska M, Chojnacki J, Wasylecka M, Dziki L, Morawiec J, Blasiak J. Polymorphisms in RAD51, XRCC2 and XRCC3 genes of the homologous recombination repair in colorectal cancer - a case control study. Mol Biol Rep. 2011;38:2849-54.
Romanowicz-Makowska H, Samulak D, Michalska M, Sporny S, Langner E, Dziki A, Sychowski R, Smolarz B. RAD51 gene polymorphisms and sporadic colorectal cancer risk in Poland. Pol J Pathol.2012;63:193-8.
Brooks J, Shore RE, Zeleniuch-Jacquotte A. Polymorphisms in RAD51, XRCC2, and XRCC3 are not related to breast cancer risk. Cancer Epidemiol Biomarkers Prev 2008;17(4):1016-9.
Cetinkunar S, Gök I, Celep RB, Ilhan D, Erdem H, Bilgin BC, Aktimur R. The effect of polymorphism in DNA repair genes RAD51 and XRCC2 in colorectal cancer in Turkish population. Int J Clin Exp Med. 2015;8(2):2649-55.
Gök I, Baday M, Çetinkünar S, Kiliç K, Bilgin BÇ. Polymorphisms in DNA repair genes XRCC2 and XRCC3 risk of gastric cancer in Turkey. Bosn J Basic Med Sci. 2014;14(4):214-8.
Yılmaz M, Ozic C, Gok I. Principles of Nucleic Acid Separation by Agarose Gel Electrophoresis. In: Magdeldin S, editor. Gel Electrophoresis Principles and Basics. Rijeka: InTech Press; 2012. p. 33-40.
Zhou J, Liu ZY, Li CB, Gao S, Ding LH, Wu XL, Wang ZY. Genetic polymorphisms of DNA repair pathways influence the response to chemotherapy and overall survival of gastric cancer. Tumour Biol 2015;36(4):3017-23
Szkandera J, Absenger G, Liegl-Atzwanger B, Pichler M, Stotz M, Gerger S, Zacherl M, Renner W, Haijun M, Leithner A, Gerger A. Common gene variants in RAD51, XRCC2 and XPD are not associated with clinical outcome in soft-tissue sarcoma patients. Cancer Epidemiol 2013;37(6):1003-9.
Pratesi N, Mangoni M, Mancini I, Paiar F, Simi L, Livi L, Cassani S, Buglione Polli C, Saieva C, Magrini SM, Biti G, Pazzagli M, Orlando C. Association between single nucleotide polymorphisms in the XRCC1 and RAD51 genes and clinical radiosensitivity in head and neck cancer. Radiother Oncol. 2011;99(3):356-61.
Schlade-Bartusiak K, Rozik K, Laczmanska I, Ramsey D, Sasiadek M. Influence of GSTT1, mEH, CYP2E1 and RAD51 polymorphisms on diepoxybutane-induced SCE frequency in cultured human lymphocytes. Mutat Res. 2004;558(1-2):121-30.
Nogueira A, Catarino R, Faustino I, Nogueira-Silva C, Figueiredo T, Lombo L, Hilário-Silva I, Pereira D, Medeiros R. Role of the RAD51 G172T polymorphism in the clinical outcome of cervical cancer patients under concomitant chemoradiotherapy. Gene. 2012;504(2):279-83.
Sliwinski T, Krupa R, Majsterek I. Polymorphisms of the BRCA2 and RAD51 genes in breast cancer. Breast Cancer Res Treat. 2005;94(2):105-9.
Zhang BB, Wang DG, Xuan C, Sun GL, Deng KF. Genetic 135G/C polymorphism of RAD51 gene and risk of cancer:a meta-analysis of 28,956 cases and 28,372 controls. Famil. Cancer. 2014;13(4):515-26.
Coghlin C, Murray GI. Progress in the development of protein biomarkers of oesophageal and gastric cancers. Proteomics Clin Appl. 2016;10(4):532-45.
Fan XJ, Ren PL, Lu ZJ, Zhao S, Yang XL, Liu J.The study of esophageal cancer risk associated with polymorphisms of DNA damage repairgenes XRCC4 and RAD51. Sichuan Da Xue Xue Bao Yi Xue Ban. 2013;44(4):568-72.
Korak T, Ergul E, Uren N, Altinok D, Simsek T, Utkan NZ, Zafer N, Gulluoglu CB, Sazci A. RAD51 (rs1801320) gene polymorphism and breast cancer risk
in Turkish population. Int J Clin Exp Pathol. 2017;10(2):2181-6.
Wang W, Li JL, He XF, Li AP, Cai YL, Xu N, Sun SM, Wu BY. Association between the RAD51 135 G>C polymorphism and risk of cancer: a meta-analysis of 19,068 cases and 22,630 controls. PlosOne. 2013;8(9):e75153.