Impact of XRCC2 Arg188His Polymorphism on Cancer Susceptibility: a Meta-analysis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Mar 14

PMID 24621646

Citations 16

Authors

Yazhou He

Yuanchuan Zhang

Chengwu Jin

Xiangbing Deng

Mingtian Wei

Qingbin Wu

Tinghan Yang

Yanhong Zhou

Ziqiang Wang

Affiliations

Soon will be listed here.

Abstract

Background: Association between the single nucleotide polymorphism rs3218536 (known as Arg188His) located in the X-ray repair cross complementing group 2 (XRCC2) gene and cancer susceptibility has been widely investigated. However, results thus far have remained controversial. A meta-analysis was performed to identify the impact of this polymorphism on cancer susceptibility.

Methods: PubMed and Embase databases were searched systematically until September 7, 2013 to obtain all the records evaluating the association between the XRCC2 Arg188His polymorphism and the risk of all types of cancers. We used the odds ratio (OR) as measure of effect, and pooled the data in a Mantel-Haenszel weighed random-effects meta-analysis to provide a summary estimate of the impact of this polymorphism on breast cancer, ovarian cancer and other cancers. All the analyses were carried out in STATA 12.0.

Results: With 30868 cases and 38656 controls, a total of 45 case-control studies from 26 publications were eventually included in our meta-analysis. No significant association was observed between the XRCC2 Arg188His polymorphism and breast cancer susceptibility (dominant model: OR = 0.94, 95%CI = 0.86-1.04, P = 0.232). However, a significant impact of this polymorphism was detected on decreased ovarian cancer risk (dominant model: OR = 0.83, 95%CI = 0.73-0.95, P = 0.007). In addition, we found this polymorphism was associated with increased upper aerodigestive tract (UADT) cancer susceptibility (dominant model: OR = 1.51, 95%CI = 1.04-2.20, P = 0.032).

Conclusion: The Arg188His polymorphism might play different roles in carcinogenesis of various cancer types. Current evidence did not suggest that this polymorphism was directly associated with breast cancer susceptibility. However, this polymorphism might contribute to decreased gynecological cancer risk and increased UADT cancer risk. More preclinical and epidemiological studies were still imperative for further evaluation.

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References

Wang S, Cao Q, Wang X, Li B, Tang M, Yuan W . PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis. PLoS One. 2013; 8(2):e56797. PMC: 3577655. DOI: 10.1371/journal.pone.0056797. View

Curtin K, Lin W, George R, Katory M, Shorto J, Cannon-Albright L . Genetic variants in XRCC2: new insights into colorectal cancer tumorigenesis. Cancer Epidemiol Biomarkers Prev. 2009; 18(9):2476-84. PMC: 2742634. DOI: 10.1158/1055-9965.EPI-09-0187. View

West S . Molecular views of recombination proteins and their control. Nat Rev Mol Cell Biol. 2003; 4(6):435-45. DOI: 10.1038/nrm1127. View

Novais Bastos H, Antao M, Silva S, Azevedo A, Manita I, Teixeira V . Association of polymorphisms in genes of the homologous recombination DNA repair pathway and thyroid cancer risk. Thyroid. 2009; 19(10):1067-75. DOI: 10.1089/thy.2009.0099. View

Zhang Y, Zhang J, Deng Y, Tian C, Li X, Huang J . Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and cancer risk: a meta-analysis. Cancer. 2011; 117(18):4312-24. DOI: 10.1002/cncr.25979. View

Beesley J, Jordan S, Spurdle A, Song H, Ramus S, Kjaer S . Association between single-nucleotide polymorphisms in hormone metabolism and DNA repair genes and epithelial ovarian cancer: results from two Australian studies and an additional validation set. Cancer Epidemiol Biomarkers Prev. 2007; 16(12):2557-65. PMC: 2666187. DOI: 10.1158/1055-9965.EPI-07-0542. View

Cerbinskaite A, Mukhopadhyay A, Plummer E, Curtin N, Edmondson R . Defective homologous recombination in human cancers. Cancer Treat Rev. 2011; 38(2):89-100. DOI: 10.1016/j.ctrv.2011.04.015. View

Millikan R, Player J, Decotret A, Tse C, Keku T . Polymorphisms in DNA repair genes, medical exposure to ionizing radiation, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2005; 14(10):2326-34. DOI: 10.1158/1055-9965.EPI-05-0186. View

Matullo G, Guarrera S, Sacerdote C, Polidoro S, Davico L, Gamberini S . Polymorphisms/haplotypes in DNA repair genes and smoking: a bladder cancer case-control study. Cancer Epidemiol Biomarkers Prev. 2005; 14(11 Pt 1):2569-78. DOI: 10.1158/1055-9965.EPI-05-0189. View

10.

Romanowicz-Makowska H, Smolarz B, Gajecka M, Kiwerska K, Rydzanicz M, Kaczmarczyk D . Polymorphism of the DNA repair genes RAD51 and XRCC2 in smoking- and drinking-related laryngeal cancer in a Polish population. Arch Med Sci. 2013; 8(6):1065-75. PMC: 3542498. DOI: 10.5114/aoms.2012.32417. View

11.

Khanna K, Jackson S . DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet. 2001; 27(3):247-54. DOI: 10.1038/85798. View

12.

Garcia-Quispes W, Perez-Machado G, Akdi A, Pastor S, Galofre P, Biarnes F . Association studies of OGG1, XRCC1, XRCC2 and XRCC3 polymorphisms with differentiated thyroid cancer. Mutat Res. 2011; 709-710:67-72. DOI: 10.1016/j.mrfmmm.2011.03.003. View

13.

Garcia-Closas M, Egan K, Newcomb P, Brinton L, Titus-Ernstoff L, Chanock S . Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses. Hum Genet. 2006; 119(4):376-88. DOI: 10.1007/s00439-006-0135-z. View

14.

Han J, Hankinson S, Ranu H, De Vivo I, Hunter D . Polymorphisms in DNA double-strand break repair genes and breast cancer risk in the Nurses' Health Study. Carcinogenesis. 2003; 25(2):189-95. DOI: 10.1093/carcin/bgh002. View

15.

Clarkson S, Wood R . Polymorphisms in the human XPD (ERCC2) gene, DNA repair capacity and cancer susceptibility: an appraisal. DNA Repair (Amst). 2005; 4(10):1068-74. DOI: 10.1016/j.dnarep.2005.07.001. View

16.

Romanowicz-Makowska H, Smolarz B, Polac I, Sporny S . Single nucleotide polymorphisms of RAD51 G135C, XRCC2 Arg188His and XRCC3 Thr241Met homologous recombination repair genes and the risk of sporadic endometrial cancer in Polish women. J Obstet Gynaecol Res. 2012; 38(6):918-24. DOI: 10.1111/j.1447-0756.2011.01811.x. View

17.

Han J, Hankinson S, Hunter D, De Vivo I . Genetic variations in XRCC2 and XRCC3 are not associated with endometrial cancer risk. Cancer Epidemiol Biomarkers Prev. 2004; 13(2):330-1. DOI: 10.1158/1055-9965.epi-03-0332. View

18.

Griffin C, Simpson P, Wilson C, Thacker J . Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation. Nat Cell Biol. 2000; 2(10):757-61. DOI: 10.1038/35036399. View

19.

Romanowicz-Makowska H, Smolarz B, Zadrozny M, Westfa B, Baszczynski J, Kokolaszwili G . 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. 2012; 33(2):145-50. View

20.

Webb P, Hopper J, Newman B, Chen X, Kelemen L, Giles G . Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14(2):319-23. DOI: 10.1158/1055-9965.EPI-04-0335. View