Breast Cancer Research and Treatment

, Volume 111, Issue 3, pp 549–553 | Cite as

Genetic polymorphisms of XRCC1 (codon 399) and susceptibility to breast cancer in Iranian women, a case–control study



The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. In the present study, we specifically investigated whether common genetic variant in XRCC1 (exon 10, codon Arg399Gln) was associated with an altered risk of breast cancer. The eligible cases were patients at chemotherapy unit of Nemazi hospital, Shiraz Iran, from October 1999 to August 2000 and from July 2004 to July 2005. The present study included 186 females with breast cancer. Age frequency-matched controls were randomly selected from the healthy females blood donor, according to the age distribution of the cases. A total of 187 healthy females included in the study. Using PCR-based method, the XRCC1 Arg399Gln polymorphism was determined. In control group the 399Gln allele frequency was 32.6%. The genotypic frequencies of the control subjects did not show significant deviation from Hardy-Weinberg equilibrium (χ2 = 1.683, df = 1, P > 0.05). A statistically significant association was observed in comparison between Gln/Gln and Arg/Arg genotype (OR = 2.01, 95% CI:1.02–3.94, P = 0.041). There was no linear trend for presence of 0, 1, and 2 of the 399Gln allele and risk of breast cancer (χ2 = 1.212, P = 0.271). In the recessive effect of the Gln allele (comparison between Gln/Gln vs. Arg/Arg+Arg/Gln), Gln/Gln genotype significantly increased the risk of breast cancer (OR = 2.31, 95% CI:1.21–4.35, P = 0.010). In the dominant effect of the Gln allele (comparison between Gln/Gln+Arg/Gln vs. Arg/Arg), Gln/Gln+Arg/Gln genotypes was not associated with the risk of breast cancer (OR = 0.95, 95% CI:0.63–1.42, P = 0.799). It is concluded that 399Gln allele may act as a recessive allele and increase the breast cancer risk.


Breast cancer Genetic polymorphism Iran Risk XRCC1 



The authors are indebted to the participants for their close cooperation. The authors are indebted to Dr. Maryam Ansari-Lari and Dr. Hassan Mohabtkar for critical reading of the manuscript and for their contribution in discussion.


  1. 1.
    Hung RJ, Hall J, Bernnan P, Boffestta P (2005) Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review. Am J Epidemiol 162:925–942PubMedCrossRefGoogle Scholar
  2. 2.
    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 21:965–971PubMedCrossRefGoogle Scholar
  3. 3.
    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 519:93–101PubMedGoogle Scholar
  4. 4.
    Matullo G, Palli D, Peluso M, Guarrera S, Carturan S, Celentano E, Krogh V, Munnia A, Tumino R, Polidoro S, Piazza A, Vineis P (2001) XRCC1, XRCC3, XPD gene polymorphisms, smoking and 32P-DNA adducts in a sample of healthy subjects. Carcinogenesis 22:1437–1445PubMedCrossRefGoogle Scholar
  5. 5.
    Relton CL, Daniel CP, Fisher A, Chase DS, Burn J, Tawn EJ (2002) Polymorphisms of the DNA repair gene XRCC1 and the frequency of somatic mutations of the glycophorin A locus in newborns. Mutat Res 502:61–68PubMedGoogle Scholar
  6. 6.
    Hu Z, Ma H, Chen F, Wei Q, Shen H (2001) XRCC1 polymorphisms and cancer risk: a meta-analysis of 38 case–control studies. Cancer Epidemiol Biomarkers Prev 14:1810–1818CrossRefGoogle Scholar
  7. 7.
    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 10:217–222PubMedGoogle Scholar
  8. 8.
    Kim SU, Park SK, Yoo KY, Yoon KS, Choi JY, Seo JS, Park WY, Kim JH, Noh DY, Ahn SH, Choe KJ, Strickland PT, Hiryonen A, Kang D (2002) XRCC1 genetic polymorphism and breast cancer risk. Pharmacogenetics 12:335–338PubMedCrossRefGoogle Scholar
  9. 9.
    Moullan N, Cox DG, Angele S, Romestaing P, Gerard JP, Hall J (2003) Polymorphisms in the DNA repair gene XRCC1, breast cancer risk, and response to radiotherapy. Cancer Epidemiol Biomarkers Prev 12:1168–1174PubMedGoogle Scholar
  10. 10.
    Figueiredo JC, Knight JA, Briollais L, Andrulis IL, Ozcelik H (2004) Polymorphisms XRCC1-R399Q and XRCC3-T241M and the risk of breast cancer at the Ontario site of the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev 13:583–591PubMedGoogle Scholar
  11. 11.
    Forsti A, Angelini S, Festa F, Sanyal S, Zhang Z, Grzybowska E, Pamula J, Pekala W, Zientek H, Hemminki K, Kumar R (2004) Single nucleotide polymorphisms in breast cancer. Oncol Rep 11:917–922PubMedGoogle Scholar
  12. 12.
    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 89:15–21PubMedCrossRefGoogle Scholar
  13. 13.
    Thyagarajan B, Anderson KE, Folsom AR, Jacobs DR Jr, Lynch CF, Bargaje A, Khalig W, Gross MD (2006) No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa Women’s Health Study. Cancer Detect Prev 30:313–321PubMedCrossRefGoogle Scholar
  14. 14.
    Abdel-Rahman SZ, El-Zein RA (2000) The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by tobacco-specific nitrosamine NNK. Cancer Lett 159:63–71PubMedCrossRefGoogle Scholar
  15. 15.
    Saadat M (2006) Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and susceptibility to gastric cancer: a meta-analysis. Cancer Sci 97:505–509PubMedCrossRefGoogle Scholar
  16. 16.
    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 54:267–283PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • Mostafa Saadat
    • 1
    • 2
  • Leila Kohan
    • 1
    • 3
  • Shahpour Omidvari
    • 4
  1. 1.Department of Biology, College of SciencesShiraz UniversityShirazIran
  2. 2.Institute of BiotechnologyShiraz UniversityShirazIran
  3. 3.Department of BiologyKhatam UniversityTehranIran
  4. 4.Department of ChemotherapyShiraz University of Medical SciencesShirazIran

Personalised recommendations