Skip to main content

Advertisement

SpringerLink
Log in

Haplotype analysis of XRCC1 (at codons 194 and 399) and susceptibility to breast cancer, a meta-analysis of the literatures

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

To clarify the association between XRCC1 haplotypes and susceptibility to breast cancer, a meta-analysis of case–control studies were conducted. Eligible studies were identified by searching several databases for relevant reports published before March 2010. In total, 10 studies were included in the present meta-analysis. XRCC1 haplotypes for Arg194Trp and Arg399Gln polymorphisms were included in the analysis. The association was measured using random-effect model or fixed-effect model odds ratio (OR) combined with 95% confidence intervals (CIs) according to the between studies’ heterogeneity. Large between-study heterogeneity was observed (Q = 25.587, df = 9, P < 0.001). The meta-analysis showed a borderline increased risk of breast cancer associated with the Arg194-Gln399 haplotype versus the Arg194-Arg399 haplotype (OR = 1.07, 95% CI: 1.01–1.14). There was no significant association between XRCC1 haplotypes and risk of breast cancer among Caucasoid subjects. In the next step, studies were classified according to geographical locations. Studies reported form Western populations did not show heterogeneity, and the Arg194-Gln399 haplotype was not associated with risk of breast cancer in comparison with the Arg194-Arg399 haplotype (OR = 1.02, 95% CI: 0.95–1.09). Among studies reported form Asian countries, significant heterogeneity was observed. After excluding of one study which did not show linkage disequilibrium, heterogeneity between studies decreased and haplotype Arg194-Gln399 revealed significant association with increased risk of breast cancer compared with haplotype Arg194-Arg399 (OR = 1.26, 95% CI: 1.04–1.50). There was no significant association between Trp194-Arg399 haplotype and risk of breast cancer, neither in Western nor Asian countries. The present meta-analysis has indicated that the Arg194-Gln399 haplotype of XRCC1 might be a risk factor for breast cancer in Asian countries.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sancar A, Lindsey-Boltz LA, Unsal-Kaçmaz K, Linn S (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73:39–85

    Article  PubMed  CAS  Google Scholar 

  2. Christmann M, Tomicic MT, Roos WP, Kaina B (2003) Mechanisms of human DNA repair: an update. Toxicology 193:3–34

    Article  PubMed  CAS  Google Scholar 

  3. Caldecott KW, Aoufouchi S, Johnson P, Shall S (1996) XRCC1 polypeptide interacts with DNA polymerase and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular “nick sensor” in vitro. Nucleic Acids Res 24:4387–4397

    Article  PubMed  CAS  Google Scholar 

  4. Caldecott KW, McKeown CK, Tucker JD, Ljungquist S, Thompson LH (1994) An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III. Mol Cell Biol 14:68–76

    PubMed  CAS  Google Scholar 

  5. Tebbes RS, Flannery ML, Meneses JJ, Hartmann A, Tucker JD, Thompson LH, Cleaver JE, Pedersen RA (1999) Requirement for the Xrcc1 DNA base excision repair gene during early mouse development. Dev Biol 208:513–529

    Article  Google Scholar 

  6. Tebbes RS, Thompson LH, Cleaver JE (2003) Rescue of Xrcc1 knockout mouse embryo lethality by trans gene-complementation. DNA Repair (Amst.) 2:1405–1417

    Article  CAS  Google Scholar 

  7. Caldecott KW (2003) XRCC1 and DNA strand break repair. DNA Repair (Amst) 2:955–969

    Article  CAS  Google Scholar 

  8. Ladiges WC (2006) Mouse models of XRCC1 DNA repair polymorphisms and cancer. Oncogene 25:1612–1619

    Article  PubMed  CAS  Google Scholar 

  9. 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 58:604–608

    PubMed  CAS  Google Scholar 

  10. Hu JJ, Smith TR, Miller MS, Lohman K, Case LD (2002) Genetic regulation of ionizing radiation sensitivity and breast cancer risk. Environ Mol Mutagen 39:208–215

    Article  PubMed  CAS  Google Scholar 

  11. Lunn RM, Langlois RG, Hsieh LL, Thompson CL, Bell DA (1999) XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res 59:2557–2561

    PubMed  CAS  Google Scholar 

  12. Matullo G, Guarrera S, Carturan S, Peluso M, Davico L, Piazza A, Vineis P (2001) DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study. Int J Cancer 92:562–567

    Article  PubMed  CAS  Google Scholar 

  13. Shen MR, Zdzienicka MZ, Mohrenweiser H, Thompson LH, Thelen MP (1998) Mutations in hamster single-strand break repair gene XRCC1 causing defective DNA. Nucleic Acids Res 26:1032–1037

    Article  PubMed  CAS  Google Scholar 

  14. Duell EJ, Wiencke JK, Cheng TJ, Varkonvi A, Zuo ZF, Ashok TD, Mark EJ, Wain JC, Christiani DC, Kelse KT (2000) Polymorphisms in the DNA repair gene XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 21:965–971

    Article  PubMed  CAS  Google Scholar 

  15. Hu JJ, Smith TR, Miller MS, Mohreweiser HW, Golden A, Cae LD (2001) Amino aid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis 22:917–922

    Article  PubMed  CAS  Google Scholar 

  16. Lei YC, Hwang SJ, Chang CC, Kuo HW, Luo JC, Chang MJW, Cheng TJ (2002) Effects on sister chromatid exchange frequency of polymorphisms in DNA repair gene XRCC1 in smokers. Mutat Res 519:93–101

    PubMed  CAS  Google Scholar 

  17. Wang Y, Spitz MR, Zhu Y, Dong Q, Shete S, Wu X (2003) From genotype to phenotype correlating XRCC1 polymorphisms with mutagen sensitivity. DNA Repair 2:901–908

    Article  PubMed  CAS  Google Scholar 

  18. Shen J, Gammon MD, Terry MB, Wang L, Wang Q, Zhang F, Teitelbaum SL, Eng SM, Sagiv SK, Gaudet MM, Neugut AI, Santella RM (2005) Polymorphisms in XRCC1 modify the association between polycyclic aromatic hydrocarbon-DNA adducts, cigarette smoking, dietary antioxidants, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 14:336–342

    Article  PubMed  CAS  Google Scholar 

  19. Qu T, Morii E, Oboki K, Lu Y, Morimoto K (2005) Micronuclei in EM9 cells expressing polymorphic forms of human XRCC1. Cancer Lett 221:91–95

    Article  PubMed  CAS  Google Scholar 

  20. Au WW, Salama SA, Sierra-Torres CH (2003) Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Toxicogenomics 111:1843–1850

    CAS  Google Scholar 

  21. Tuimala J, Szekely G, Wikman H, Jarventaus H, Hirvonen A, Gundy S, Norppa H (2004) Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: effects on levels of sister chromatid exchanges and chromosomal aberrations. Mutat Res 554:319–333

    PubMed  CAS  Google Scholar 

  22. Duell EJ, Millikan RC, Pittman GS, Winkel S, Lunn RM, Tse CK, Eaton A, Mohrenweiser HW, Newman B, BelL DA (2001) Polymorphisms in the DNA repair gene XRCC1 and breast cancer. Cancer Epidemiol Biomarkers Prev 10:217–222

    PubMed  CAS  Google Scholar 

  23. Saadat M, Kohan L, Omidvari S (2008) Genetic polymorphisms of XRCC1 (codon Arg399Gln) and susceptibility to breast cancer in Iranian women, a case-control study. Breast Cancer Res Treat 111:549–553

    Article  PubMed  CAS  Google Scholar 

  24. Loizidou MA, Michael T, Neuhausen SL, Newbold RF, Marcou Y, Kakouri E, Daniel M, Papadopoulos P, Malas S, Kyriacou K, Hadjisavvas A (2008) Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus. Breast Cancer Res Treat 112:575–579

    Article  PubMed  CAS  Google Scholar 

  25. Smith TR, Miller MS, Lohman K, Lange EM, Case LD, Mohrenweiser HW, Hu JJ (2003) Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer Lett 90:183–190

    Article  Google Scholar 

  26. Kang D (2003) Genetic polymorphisms and cancer susceptibility of breast cancer in Korean women. J Biochem Mol Biol 36:28–34

    PubMed  CAS  Google Scholar 

  27. Deligezer U, Dalay N (2004) Association of the XRCC1 gene polymorphisms with cancer risk in Turkish breast cancer patients. Exp Mol Med 36:572–575

    PubMed  CAS  Google Scholar 

  28. Chacko P, Rajan B, Joseph T, Mathew BS, Pillai MR (2005) Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to breast cancer. Breast Cancer Res Treat 89:15–21

    Article  PubMed  CAS  Google Scholar 

  29. Metsola K, Kataja V, Sillanpää P, Siivola P, Heikinheimo L, Eskelinen M, Kosma VM, Uusitupa M, Hirvonen A (2005) XRCC1 and XPD genetic polymorphisms, smoking and breast cancer risk in a Finnish case-control study. Breast Cancer Res 7:R987–R997

    Article  PubMed  CAS  Google Scholar 

  30. Brewster AM, Jorgensen TJ, Ruczinski I, Huang HY, Hoffman S, Thuita L, Newschaffer C, Lunn RM, Bell D, Helzlsouer KJ (2006) Polymorphisms of the DNA repair genes XPD (Lys751Gln) and XRCC1 (Arg399Gln and Arg194Trp): relationship to breast cancer risk and familial predisposition to breast cancer. Breast Cancer Res Treat 95:73–80

    Article  PubMed  CAS  Google Scholar 

  31. Moullan N, Cox DG, Angèle S, Romestaing P, Gérard JP, Hall J (2003) Polymorphisms in the DNA repair gene XRCC1, breast cancer risk, and response to radiotherapy. Cancer Epidemiol Biomarkers Prev 12:1168–1174

    PubMed  CAS  Google Scholar 

  32. Han J, Hankinson SE, De Vivo I, Spiegelman D, Tamimi RM, Mohrenweiser HW, Colditz GA, Hunter DJ (2003) A prospective study of XRCC1 haplotypes and their interaction with plasma carotenoids on breast cancer risk. Cancer Res 63:8536–8541

    PubMed  CAS  Google Scholar 

  33. Pachkowski BF, Winkel S, Kubota Y, Swenberg JA, Millikan RC, Nakamura J (2006) XRCC1 genotype and breast cancer: functional studies and epidemiologic data show interactions between XRCC1 codon Arg194Trp His and smoking. Cancer Res 66:2860–2868

    Article  PubMed  CAS  Google Scholar 

  34. Berm R, Cox DG, Chapot B, Moullan N, Romestaing P, Gerard JP, Pisani P, Hall J (2006) The XRCC1-77T-C variant: haplotypes breast cancer risk, response to radiotherapy and the cellular response to DNA damage. Carcinogenesis 27:2469–2474

    Article  Google Scholar 

  35. Kohan L, Omidvari S, Saadat M (2006) Combination of XRCC1, GSTM1, and GSTM1 genetic polymorphisms and susceptibility to male breast cancer. Int J Cancer Res 2:415–419

    Article  CAS  Google Scholar 

  36. Silva SN, Moita R, Azevedo AP, Gouveia R, Manital I, Pina JE, Rueff J, Gaspar J (2007) Menopausal age and XRCC1 gene polymorphisms: role in breast cancer risk. Cancer Detect Prev 31:303–309

    Article  PubMed  CAS  Google Scholar 

  37. Mitra AK, Singh N, Singh A, Garg VK, Agarwal A, Sharma M, Chaturvedi R, Rath SK (2008) Association of polymorphisms in base excision repair genes with the risk of breast cancer: a case-control study in north Indian women. Oncol Res 17:127–135

    PubMed  Google Scholar 

  38. Sangrajrang S, Schmezer P, Burkholder I, Waas P, Boffetta P, Brennan P, Bartsch H, Wiangnon S, Popanda O (2008) Polymorphisms in three base excision repair genes and breast cancer risk in Thai women. Breast Cancer Res Treat 111:279–288

    Article  PubMed  CAS  Google Scholar 

  39. Saadat M, Kohan L, Saadat I, Omidvari S (2009) Haplotype analysis of XRCC1 (at codons 194 and 399) and breast cancer risk, a case-control study. Comp Clin Path. doi: 10.1007/s00580-009-0875-y

  40. Sterpone S, Mastellone V, Padua L, Novelli F, Patrono C, Cornetta T, Giammarino D, Donato V, Testa A, Cozzi R (2010) Single-nucleotide polymorphisms in BER and HRR genes, XRCC1 haplotypes and breast cancer risk in Caucasian women. J Cancer Res Oncol 136:631–636

    Article  CAS  Google Scholar 

  41. Jin MJ, Chen K, Zhang SS, Zhang YJ, Ren YJ, Xu H, Yao KY, Li QL, Ma XY (2006) Association of single nucleotide polymorphisms and haplotypes in DNA repair gene XRCC1 with susceptibility of breast cancer. Zhejiang Da Xue Xue Bao Yi Xue Ban 35:370–376 [Chinese]

    PubMed  CAS  Google Scholar 

  42. Saadat M, Ansari-Lari M (2008) Polymorphism of XRCC1 (at codon 399) and susceptibility to breast cancer, a meta-analysis of the literatures. Breast Cancer Res Treat 115:137–144

    Article  PubMed  CAS  Google Scholar 

  43. Huang Y, Li L, Yu L (2009) XRCC1 Arg399Gln, Arg194Trp and Arg280His polymorphisms in breast cancer risk: a meta-analysis. Mutagenesis 24:331–339

    Article  PubMed  CAS  Google Scholar 

  44. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Controlled Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  45. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

  46. Mohamadynejad P, Saadat M (2008) Genetic polymorphisms of XRCC1 (at codons 194 and 399) in Shiraz population (Fars province, southern Iran). Mol Biol Rep 35:669–672

    Article  PubMed  CAS  Google Scholar 

  47. Yin M, Tan D, Wei Q (2009) Genetic variants of the XRCC1 gene and susceptibility to esophageal cancer: a meta-analysis. Int J Clin Exp Med 2:26–35

    PubMed  CAS  Google Scholar 

  48. Geng J, Zhang Q, Zhu C, Wang J, Chen L (2009) XRCC1 genetic polymorphism Arg399Gln and prostate cancer risk: a meta-analysis. Urology 74:648–653

    Article  PubMed  Google Scholar 

  49. Hu Z, Ma H, Chen F, Wei Q, Shen H (2005) XRCC1 polymorphisms and cancer risk: a meta-analysis of 38 case-control studies. Cancer Epidemiol Biomarkers Prev 14:1810–1818

    Article  PubMed  CAS  Google Scholar 

  50. Kiyohara C, Takayama K, Nakanishi Y (2006) Association of genetic polymorphisms in the base excision repair pathway with lung cancer risk: a meta-analysis. Lung Cancer 54:267–283

    Article  PubMed  Google Scholar 

  51. Moore DJ, Taylor RM, Clements P, Caldecott KW (2000) Mutation of a BRCT domain selectively disrupts DNA single strand break repair in noncycling Chinese hamster ovary cells. Proc Natl Acad Sci USA 97:13649–13654

    Article  PubMed  CAS  Google Scholar 

  52. Masoudi M, Saadat I, Omidvari S, Saadat M (2010) Additive effects of genetic variants of xenobiotic detoxification enzymes and DNA repair gene XRCC1 on the susceptibility to breast cancer. Breast Cancer Res Treat 120:263–265

    Article  PubMed  Google Scholar 

  53. Masoudi M, Saadat I, Omidvari S, Saadat M (2009) Genetic polymorphisms of GSTO2, GSTM1, and GSTT1 and risk of gastric cancer. Mol Biol Rep 36:781–784

    Article  PubMed  CAS  Google Scholar 

  54. Saadat M (2006) Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and susceptibility to gastric cancer: a meta-analysis. Cancer Sci 97:505–509

    Article  PubMed  CAS  Google Scholar 

  55. Saadat I, Saadat M (2001) Glutathione S-transferase M1 and T1 null genotypes and the risk of gastric and colorectal cancers. Cancer Lett 169:21–26

    Article  PubMed  CAS  Google Scholar 

  56. Saadat M, Saadat I, Saboori Z, Emad A (2004) Combination of CC16, GSTM1 and GSTT1 polymorphisms is associated with asthma. J Allergy Clin Immunol 113:996–998

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The author is indebted to Dr. Maryam Ansari-Lari for critical reading of the manuscript and for her contribution in discussion. This study was supported by Shiraz University. The authors have no conflict of interest in relation to this study.

Author information

Authors and Affiliations

  1. Department of Biology, College of Sciences, Shiraz University, Shiraz, 71454, Iran

    Mostafa Saadat

Authors
  1. Mostafa Saadat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mostafa Saadat.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saadat, M. Haplotype analysis of XRCC1 (at codons 194 and 399) and susceptibility to breast cancer, a meta-analysis of the literatures. Breast Cancer Res Treat 124, 785–791 (2010). https://doi.org/10.1007/s10549-010-0895-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-010-0895-y

Keywords

Search

Navigation