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XPD Lys751Gln polymorphism and breast cancer susceptibility: a meta-analysis involving 28,709 subjects

  • Epidemiology
  • Published:
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Abstract

Published data on the association between Xeroderma Pigmentosum complementation group D (XPD) Lys751Gln polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 30 studies including 14,283 cases and 14,426 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with XPD 751Gln allele when all studies were pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR = 1.13, 95% CI = 1.02–1.25; Gln/Gln vs. Lys/Lys: OR = 1.21, 95% CI = 1.06–1.38; dominant model: OR = 1.16, 95% CI = 1.05–1.29; and recessive model: OR = 1.14, 95% CI = 1.02–1.27). In the subgroup analysis by ethnicity, borderline significantly increased risks were found for Caucasians (Lys/Gln vs. Lys/Lys: OR = 1.09, 95% CI = 0.98–1.22; dominant model: OR = 1.10, 95% CI = 0.99–1.22) and significantly increased risks were found for Africans in dominant model (OR = 1.10, 95% CI = 1.04–1.15). When stratified by study design, statistically significantly elevated risk was found in population-based studies (Lys/Gln vs. Lys/Lys: OR = 1.10, 95% CI = 1.01–1.20; Gln/Gln vs. Lys/Lys: OR = 1.15, 95% CI = 1.01–1.31; dominant model: OR = 1.12, 95% CI = 1.03–1.23). In conclusion, this meta-analysis suggests that the XPD 751Gln allele is a low-penetrant risk factor for developing breast cancer.

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References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  2. Lichtenstein P, Holm NV, Verkasalo PK (2000) Environmental and heritable factors in the causation of cancer. N Engl J Med 343:78–85

    Article  CAS  PubMed  Google Scholar 

  3. Flejter WL, McDaniel LD, Johns DR (1992) Correction of xeroderma pigmentosum complementation group D mutant cell phenotypes by chromosome and gene transfer: involvement of the human ERCC2 DNA repair gene. Proc Natl Acad Sci USA 89:261–265

    Article  CAS  PubMed  Google Scholar 

  4. Clarkson SG, Wood RD (2005) Polymorphisms in the human XPD (ERCC2) gene, DNA repair capacity and cancer susceptibility: an appraisal. DNA Repair 4:1068–1074

    Article  CAS  PubMed  Google Scholar 

  5. Justenhoven C, Hamann U, Pesch B (2004) ERCC2 genotypes and a corresponding haplotype are linked with breast cancer risk in a German population. Cancer Epidemiol Biomarkers Prev 13:2059–2064

    CAS  PubMed  Google Scholar 

  6. Shen MR, Jones IM, Mohrenweiser H (1998) Non-conservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 58:604–608

    CAS  PubMed  Google Scholar 

  7. Tang D, Cho S, Rundle A, Chen S, Phillips D, Zhou J, Hsu Y, Schnabel F, Estabrook A, Perera FP (2002) Polymorphisms in the DNA repair enzyme XPD are associated with increased levels of PAH-DNA adducts in a case-control study of breast cancer. Breast Cancer Res Treat 75:159–166

    Article  CAS  PubMed  Google Scholar 

  8. Brewster AM, Alberg AJ, Strickland PT, Hoffman SC, Helzlsouer K (2004) XPD polymorphism and risk of subsequent cancer in individuals with nonmelanoma skin cancer. Cancer Epidemiol Biomark Prev 13:1271–1275

    CAS  Google Scholar 

  9. 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 11:917–922

    PubMed  Google Scholar 

  10. Justenhoven C, Hamann U, Pesch B, Harth V, Rabstein S, Baisch C, Vollmert C, Illig T, Ko YD, Brüning T, Brauch H (2004) ERCC2 genotypes and a corresponding haplotype are linked with breast cancer risk in a German population. Cancer Epidemiol Biomark Prev 13:2059–2064

    CAS  Google Scholar 

  11. Shi Q, Wang LE, Bondy ML, Brewster A, Singletary SE, Wei Q (2004) Reduced DNA repair of benzo[a]pyrene diol epoxide-induced adducts and common XPD polymorphisms in breast cancer patients. Carcinogenesis 25:1695–1700

    Article  CAS  PubMed  Google Scholar 

  12. Terry MB, Gammon MD, Zhang FF, Eng SM, Sagiv SK, Paykin AB, Wang Q, Hayes S, Teitelbaum SL, Neugut AI, Santella RM (2004) Polymorphism in the DNA repair gene XPD, polycyclic aromatic hydrocarbon-DNA adducts, cigarette smoking, and breast cancer risk. Cancer Epidemiol Biomark Prev 13:2053–2058

    CAS  Google Scholar 

  13. Dufloth RM, Costa S, Schmitt F, Zeferino LC (2005) DNA repair gene polymorphisms and susceptibility to familial breast cancer in a group of patients from Campinas, Brazil. Genet Mol Res 4:771–782

    CAS  PubMed  Google Scholar 

  14. Kuschel B, Chenevix-Trench G, Spurdle AB, Chen X, Hopper JL, Giles GG (2005) Common polymorphisms in ERCC2 (Xeroderma pigmentosum D) are not associated with breast cancer risk. Cancer Epidemiol Biomark Prev 14:1828–1831

    Article  CAS  Google Scholar 

  15. Metsola K, Kataja V, Sillanp 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  CAS  PubMed  Google Scholar 

  16. Zhang L, Zhang Z, Yan W (2005) Single nucleotide polymorphisms for DNA repair genes in breast cancer patients. Clin Chim Acta 359:150–155

    Article  CAS  PubMed  Google Scholar 

  17. 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  CAS  PubMed  Google Scholar 

  18. Debniak T, Scott RJ, Huzarski T, Byrski T, Masoj B, van de Wetering T (2006) XPD common variants and their association with melanoma and breast cancer risk. Breast Cancer Res Treat 98:209–215

    Article  CAS  PubMed  Google Scholar 

  19. Mechanic LE, Millikan RC, Player J, de Cotret AR, Winkel S, Worley K (2006) Polymorphisms in nucleotide excision repair genes, smoking and breast cancer in African Americans and whites: a population-based case–control study. Carcinogenesis 27:1377–1385

    Article  CAS  PubMed  Google Scholar 

  20. Onay VU, Briollais L, Knight JA, Shi E, Wang Y, Wells S, Li H, Rajendram I, Andrulis IL, Ozcelik H (2006) SNP–SNP interactions in breast cancer susceptibility. BMC Cancer 6:114

    Article  PubMed  Google Scholar 

  21. Shen J, Desai M, Agrawal M, Kennedy DO, Senie RT, Santella RM, Terry MB (2006) Polymorphisms in nucleotide excision repair genes and DNA repair capacity phenotype in sisters discordant for breast cancer. Cancer Epidemiol Biomark Prev 15:1614–1619

    Article  CAS  Google Scholar 

  22. Costa S, Pinto D, Pereira D, Rodrigues H, Cameselle-Teijeiro J, Medeiros R, Schmitt F (2007) DNA repair polymorphisms might contribute differentially on familial and sporadic breast cancer susceptibility: a study on a Portuguese population. Breast Cancer Res Treat 103:209–217

    Article  CAS  PubMed  Google Scholar 

  23. Romanowicz-Makowska H, Sobczuk A, Smolarz B, Fiks T, Kulig A (2007) XPD Lys751Gln polymorphism analysis in women with sporadic breast cancer. Pol J Pathol 58:245–249

    CAS  PubMed  Google Scholar 

  24. Bernard-Gallon D, Bosviel R, Delort L, Fontana L, Chamoux A, Rabiau N, Kwiatkowski F, Chalabi N, Satih S, Bignon YJ (2008) DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk. Mol Cancer 7:36

    Article  PubMed  Google Scholar 

  25. Kipikasová L, Wolaschka T, Bohus P, Baumohlová H, Bober J, Blazejová J (2008) Polymorphisms of the XRCC1 and XPD genes and breast cancer risk: a case–control study. Pathol Oncol Res 14:131–135

    Article  PubMed  Google Scholar 

  26. Li J, Jin W, Chen Y, Di G, Wu J, Shao ZM (2008) Genetic polymorphisms in the DNA repair enzyme ERCC2 and breast tumour risk in a Chinese population. J Int Med Res 36:479–488

    CAS  PubMed  Google Scholar 

  27. Rajaraman P, Bhatti P, Doody MM, Simon SL, Weinstock RM, Linet MS (2008) Nucleotide excision repair polymorphisms may modify ionizing radiation-related breast cancer risk in US radiologic technologists. Int J Cancer 123:2713–2716

    Article  CAS  PubMed  Google Scholar 

  28. Shore RE, Zeleniuch-Jacquotte A, Currie D, Mohrenweiser H, Afanasyeva Y, Koenig KL, Arslan AA, Toniolo P, Wirgin I (2008) Polymorphisms in XPC and ERCC2 genes, smoking and breast cancer risk. Int J Cancer 122:2101–2105

    Article  CAS  PubMed  Google Scholar 

  29. Smith TR, Levine EA, Freimanis RI, Akman SA, Allen GO, Hoang KN, Liu-Mares W, Hu JJ (2008) Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis 29:2132–2138

    Article  CAS  PubMed  Google Scholar 

  30. Synowiec E, Stefanska J, Morawiec Z, Blasiak J, Wozniak K (2008) Association between DNA damage, DNA repair genes variability and clinical characteristics in breast cancer patients. Mutat Res 648:65–72

    CAS  PubMed  Google Scholar 

  31. Hsu MS, Yu JC, Wang HW, Chen ST, Hsiung CN, Ding SL, Wu PE, Shen CY, Cheng CW (2009) Synergistic effects of polymorphisms in dna repair genes and endogenous estrogen exposure on female breast cancer risk. Ann Surg Oncol. doi:10.1245/s10434-009-0802-0

  32. Mitra AK, Singh N, Garg VK, Chaturvedi R, Sharma M, Rath SK (2009) Statistically significant association of the single nucleotide polymorphism (SNP) rs13181 (ERCC2) with predisposition to Squamous Cell Carcinomas of the Head and Neck (SCCHN) and Breast cancer in the north Indian population. J Exp Clin Cancer Res 28:104

    Article  PubMed  Google Scholar 

  33. Syamala VS, Syamala V, Sreedharan H, Raveendran PB, Kuttan R, Ankathil R (2009) Contribution of XPD (Lys751Gln) and XRCC1 (Arg399Gln) polymorphisms in familial and sporadic breast cancer predisposition and survival: an Indian report. Pathol Oncol Res 15:389–397

    Article  CAS  PubMed  Google Scholar 

  34. Jakubowska A, Gronwald J, Menkiszak J, Górski B, Huzarski T, Byrski T (2010) BRCA1-associated breast and ovarian cancer risks in Poland: no association with commonly studied polymorphisms. Breast Cancer Res Treat 119:201–211

    Article  PubMed  Google Scholar 

  35. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129

    Article  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  38. Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 8:15–17

    Google Scholar 

  39. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    CAS  PubMed  Google Scholar 

  40. Taylor SJ, Tweedie RI (1998) Practical estimates of the effect of publication bias in meta-analysis. Australas Epidemiol 5:14–17

    CAS  Google Scholar 

  41. Cleaver JE (2000) Common pathways for ultraviolet skin carcinogenesis in the repair and replication defective groups of xeroderma pigmentosum. J Dermatol Sci 23:1–11

    Article  CAS  PubMed  Google Scholar 

  42. Coin F, Marinoni JC, Rodolfo C (1998) Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH. Nat Genet 20:184–188

    Article  CAS  PubMed  Google Scholar 

  43. Au WW, Navasumrit P, Ruchirawat M (2004) Use of biomarkers to characterize functions of polymorphic DNA repair genotypes. Int J Hyg Environ Health 207:301–313

    Article  CAS  PubMed  Google Scholar 

  44. Vodicka P, Kumar R, Stetina R (2004) Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA. Carcinogenesis 25:757–763

    Article  CAS  PubMed  Google Scholar 

  45. Pavanello S, Pulliero A, Siwinska E (2005) Reduced nucleotide excision repair and GSTM1-null genotypes influence anti-β [α] PDE-DNA adduct levels in mononuclear white blood cells of highly PAH-exposed coke oven workers. Carcinogenesis 26:169–175

    Article  CAS  PubMed  Google Scholar 

  46. Hirschhorn JN, Lohmueller K, Byrne E (2002) A comprehensive review of genetic association studies. Genet Med 4:45–61

    Article  CAS  PubMed  Google Scholar 

  47. Wacholder S, Chanock S, Garcia-Closas M (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst 96:434–442

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Cancer Hospital, Fudan University, Shanghai, China

    Li-Xin Qiu, Jian Zhang, Xiao-Dong Zhu, Xin-Min Zhao, Kai Xue & Xi-Chun Hu

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Li-Xin Qiu, Jian Zhang, Xiao-Dong Zhu, Xin-Min Zhao, Kai Xue & Xi-Chun Hu

  3. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China

    Lei Yao

  4. Department of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China

    Chen Mao

  5. Department of Geriatrics, First Affiliated Hospital, Nanjing Medical University, Nanjing, China

    Bo Chen

  6. Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China

    Ping Zhan

  7. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui, China

    Hui Yuan

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  1. Li-Xin Qiu
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Correspondence to Li-Xin Qiu or Xi-Chun Hu.

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Qiu, LX., Yao, L., Zhang, J. et al. XPD Lys751Gln polymorphism and breast cancer susceptibility: a meta-analysis involving 28,709 subjects. Breast Cancer Res Treat 124, 229–235 (2010). https://doi.org/10.1007/s10549-010-0813-3

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