- Volume 15 Issue 23
DOI QR Code
Correlation between Selected XRCC2, XRCC3 and RAD51 Gene Polymorphisms and Primary Breast Cancer in Women in Pakistan
- Qureshi, Z. (COMSATS Institute of Information Technology Islamabad) ;
- Mahjabeen, I. (COMSATS Institute of Information Technology Islamabad) ;
- Baig, R.M. (Pir Mehr Ali Shah Arid Agriculture University) ;
- Kayani, M.A. (COMSATS Institute of Information Technology Islamabad)
- Published : 2015.01.06
Genetic polymorphisms in homologous recombination repair genes cause an abnormal development of cancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotide polymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C, XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Polymerase chain reaction-restriction fragment length polymorphism in study cohort of 306 females (156 breast cancer patients and 150 controls). We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism was associated with a significantly (OR=2.70; 95%CI (0.63-1.79); p<0.03) increased risk of breast cancer. In case of the XRCC3 gene we observed that frequency of heterozygous (OR=2.88; 95%CI (1.02-8.14); p<0.02) and homozygous (OR=1.46; 95%CI (0.89-2.40); p<0.04) genotype of Thr241Met polymorphism were significantly higher in breast cancer patients. For the Arg188His polymorphism of XRCC2, ~2fold increase in breast cancer risk (OR=1.6, 95%CI = 0.73-3.50) was associated with GA genotype with a p value for trend of 0.03. Our results suggest that the 135G/C polymorphism of the RAD51, Thr241Met polymorphism of XRCC3 and Arg188His polymorphism of XRCC2 can be independent markers of breast cancer risk in Pakistan.
- Alanazi M, Pathan AA, Ajaj SA et al (2013). DNA repair genes XRCC1, XRCC3, XPD, and OGG1 polymorphisms among the central region population of Saudi Arabia. Biol Res. 46, 161-167. https://doi.org/10.4067/S0716-97602013000200007
- Andreassi MG, Foffa I, Manfredi S, Botto N, Cioppa A, Picno E (2009). Mutation research/fundamental and molecular mechanisms of mutagenesis. Mutat Res, 666, 57-63. https://doi.org/10.1016/j.mrfmmm.2009.04.003
- 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
- Baig RM, Mahjabeen I, Sabir M, et al (2011). Genetic changes in PTEN gene and their association with breast cancer in Pakistan. Asian Pac J Cancer Prev, 12, 2365-70.
- Cole DJ, Rajendra E, Roberts-Thompson M (2011). Interrogation of the protein-protein interactions between human BRCA2 BRC repeats and RAD51 reveals atomistic determinants of affinity. PLOS Comput Biol, 7, 7.
- Economopoulos KP, Sergentanis TN (2010). XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat, 121, 439-43. https://doi.org/10.1007/s10549-009-0562-3
- Falvo E, Stigari L, Citro G, Giordano C (2011). Dose and polymorphic genes XRCC1, XRCC3 and GST play a role in the risk of article developing erythema in breast cancer patients following single shot partial breast irradiation after conservative surgery. BMC Cancer, 12, 291.
- Fayaz S, Karimmirza M, Tanhaei S, et al (2013). Increased risk of differentiated thyroid carcinoma with combined effects of homologous recombination repairgene polymorphisms in an Iranian population. Asian Pac J Cancer Prev, 14, 6727-31. https://doi.org/10.7314/APJCP.2013.14.11.6727
- Gao LB, Pan XM, Li LJ, Liang WB (2011). RAD51 135 G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies. Breast cancer Res Treat, 125, 827-35. https://doi.org/10.1007/s10549-010-0995-8
- Hasselbach L, Haase S, Fischer D (2005). Characterization of the promoter region of the human DNA-repair gene RAD51. Eur J Gynaecol Oncol, 26, 589-98.
- He Y, Zhang Y, Jin C, et al (2014). Impact of XRCC2 Arg188His polymorphism on cancer susceptibility: a meta-analysis. PLoS One, 9, 91202. https://doi.org/10.1371/journal.pone.0091202
- Hosseini M, Houshmand M, Ebrahimi A (2012). RAD51 polymorphism and breast cancer risk. Mol Bio Rep, 40, 665-8.
- Jara L, Dubois K, Gaete D (2010). Variants in DNA double strand break repair genes and risk of familial breast cancer in a South American population. Breast Cancer Res Treat, 122, 813-22. https://doi.org/10.1007/s10549-009-0709-2
- Krupa R, Synowiec E, Pawlowska E, et al (2009). Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer. Exp Mol Pathol, 87, 32-35. https://doi.org/10.1016/j.yexmp.2009.04.005
- Kuschel B, Auranen A, McBride (2002). Variants in DNA double strand break repair genes and breast cancer susceptibility. Hum Mol Genet, 11, 1433-8. https://doi.org/10.1093/hmg/11.12.1433
- Lee SA, Lee KM, Park SK, et al (2007). Genetic polymorphism of XRCC3 Thr241Met and breast cancer risk: case control study in Korean women and meta-analysis of 12 studies. Breast Cancer Res Treat, 103, 71-6. https://doi.org/10.1007/s10549-006-9348-z
- Millikan RC, Player JS, DeCotret AR, Tse C, Keku T (2005). Polymorphisms in DNA repair genes, medical exposure to ionizing radiation, and breast cancer risk. Cancer Epidemiol Biomarkers, 14, 2326-34. https://doi.org/10.1158/1055-9965.EPI-05-0186
- Parine NR, Pathan AA, Bobbarala V, et al (2012). DNA repair gene polymorphisms at XRCC1, XRCC3, XPD, and OGG1 loci in the Hyderabad population of India. Asian Pac J Cancer Prev, 13, 6469-74. https://doi.org/10.7314/APJCP.2012.13.12.6469
- Romanowicz-Makoeska H, Smolarz B, Zadrozny M (2011). Single nucleotide polymorphism in the homologous recombination repair genes and breast cancer risk in Polish women. Tohoku J Exp Med, 224, 201-8. https://doi.org/10.1620/tjem.224.201
- 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 Gynaecol Oncol, 33, 145-50.
- Shin A, Lee KM, Ahn B (2008). Genotype phenotype relationship between DNA repair gene genetic polymorphisms and DNA repair capacity. Asian Pac J Cancer Prev, 9, 501-5.
- Silva SN, Tomar M, Paulo C, et al (2010). Breast Cancer risk and common single nucleotide polymorphisms in homologous recombination DNA repair pathway genes XRCC2, XRCC3, NBS1 and RAD51. Cancer Epidemiol, 34, 85-92. https://doi.org/10.1016/j.canep.2009.11.002
- Sliwinski T, Walczak A, Przybylowska K (2010). Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population. Exp Mol Pathol, 89, 358-66. https://doi.org/10.1016/j.yexmp.2010.08.005
- Suwaki N, Klare K,Tarsounas M (2011). Rad51 paralogs: roles in DNA damage signalling, recombinational repair and tumorigenesis. Semin Cell Dev Biol, 22, 898-905. https://doi.org/10.1016/j.semcdb.2011.07.019
- Tambini CE, Spink KG, Ross CJ, Hill MA, Thacker J (2010) The importance of XRCC2 in RAD51-related DNA damage repair. DNA Repair, 9, 517-25. https://doi.org/10.1016/j.dnarep.2010.01.016
- Wang Z, Dong H, Fu Y, Ding H (2010) RAD51 135G>C polymorphism contributes to breast cancer susceptibility: a meta-analysis involving 26,444 subjects. Breast cancer Res Treat, 124, 765-9. https://doi.org/10.1007/s10549-010-0885-0
- 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 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 a Chinese population. Asian Pac J Cancer Prev, 13, 665-9. https://doi.org/10.7314/APJCP.2012.13.2.665
- XRCC3 is a promising target to improve the radiotherapy effect of esophageal squamous cell carcinoma vol.106, pp.12, 2015, https://doi.org/10.1111/cas.12820
- CYP1A1 and GSTP1 gene variations in breast cancer: a systematic review and case–control study vol.15, pp.2, 2016, https://doi.org/10.1007/s10689-015-9849-1
- Polymorphisms in Cancer Susceptibility Genes XRCC1, RAD51 and TP53 and the Risk of Breast Cancer in Serbian Women vol.31, pp.3, 2016, https://doi.org/10.5301/jbm.5000201
- Absence of the CHEK2 c.1100delC mutation in familial breast and ovarian cancer in Colombia: a case-control study vol.7, pp.2046-1402, 2018, https://doi.org/10.12688/f1000research.13368.1
- 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