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Lack of association between ATM C.1066-6T > G mutation and breast cancer risk: a meta-analysis of 8,831 cases and 4,957 controls

  • Epidemiology
  • Published:
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Abstract

Epidemiological studies have evaluated the association between ATM C.1066-6T > G (IVS10-6T > G) mutation and breast cancer risk. However, the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of 11 studies including 8,831 cases and 4,957 controls were identified. The carrier frequency of the ATM C.1066-6T > G mutation was 0.5% (45/8,831) in patients with breast cancer and 0.7% (38/4,957) in healthy controls. When all the 11 studies were pooled into the meta-analysis, there was no evidence for significant association between C.1066-6T > G mutation and breast cancer risk (OR 0.87, 95% CI 0.55–1.37). In the subgroup analyses by source of controls and family history with BRCA1/2 status, no significant association were found in any subgroup of population. When sensitivity analyses were performed, all the results were not materially altered. In summary, the meta-analysis strongly suggests that ATM C.1066-6T > G mutation is not associated with increased breast cancer risk.

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References

  1. Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y (1995) A single ataxia-telangiectasia gene with a product similar to PI-3 kinase. Science 268(5218):1749–1753

    Article  CAS  PubMed  Google Scholar 

  2. Lavin MF, Shiloh Y (1997) The genetic defect in ataxia-telangiectasia. Annu Rev Immunol 15:177–202

    Article  CAS  PubMed  Google Scholar 

  3. Swift M, Reitnauer P, Morrell D, Chase C (1987) Breast and other cancers in families with ataxia-telangiectasia. N Engl J Med 316(21):1289–1294

    Article  CAS  PubMed  Google Scholar 

  4. Borresen A, Andersen T, Tretli S, Heilberg A, Moller P (1990) Breast cancer and other cancers in Norwegian families with ataxia-telangiectasia. Genes Chromosom Cancer 2(4):339–340

    Article  CAS  PubMed  Google Scholar 

  5. Swift M, Morrell D, Massey R, Chase C (1991) Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 325(26):1831–1836

    Article  CAS  PubMed  Google Scholar 

  6. Athma P, Rappaport R, Swift M (1996) Molecular genotyping shows that ataxia-telangiectasia heterozygotes are predisposed to breast cancer. Cancer Genet Cytogenet 92(2):130–134

    Article  CAS  PubMed  Google Scholar 

  7. Inskip H, Kinlen L, Taylor A, Woods C, Arlett C (1999) Risk of breast cancer and other cancers in heterozygotes for ataxia telangiectasia. Br J Cancer 79(7–8):1304–1307

    Article  CAS  PubMed  Google Scholar 

  8. Janin N, Andrieu N, Ossaian K, Lauge A, Croquette M, Griscelli C, Debre M, Bressac-de-Paillertes B, Aurias A, Stoppa-Lyonnet D (1999) Breast cancer risk in ataxia telangiectasia (AT) heterozygotes: haplotype study in French AT families. Br J Cancer 80(7):1042–1045

    Article  CAS  PubMed  Google Scholar 

  9. Geoffroy-Perez B, Janin N, Ossian K, Lauge A, Croquette MF, Griscelli C, Debre M, Bressac-de-Paillerets B, Aurias A, Stoppa-Lyonnet D, Andrieu N (2001) Cancer risk in heterozygotes for ataxia-telangiectasia. Int J Cancer 93(2):288–293

    Article  CAS  PubMed  Google Scholar 

  10. Olsen JH, Hahnemann JM, Borresen-Dale AL, Brondum-Nielsen K, Hammarstrom L, Kleinerman R, Kaariainen H, Lonnqvist T, Sankila R, Seersholm N, Tretli S, Yuen J, Boice JD Jr, Tucker M (2001) Cancer in patients with ataxia-telangiectasia and in their relatives in the Nordic countries. J Natl Cancer Inst 93(2):121–127

    Article  CAS  PubMed  Google Scholar 

  11. Vorechovsky I, Rasio D, Luo L, Monaco C, Hammarstrom L, Webster AD, Zaloudik J, Barbanti-Brodani G, James M, Russo G (1996) The ATM gene and susceptibility to breast cancer: analysis of 38 breast tumors reveals no evidence for mutation. Cancer Res 56(12):2726–2732

    CAS  PubMed  Google Scholar 

  12. FitzGerald MG, Bean JM, Hegde SR, Unsal H, MacDonald DJ, Harkin DP, Finkelstein DM, Isselbacher KJ, Haber DA (1997) Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nat Genet 15(3):307–310

    Article  CAS  PubMed  Google Scholar 

  13. Chen J, Birkholtz GG, Lindblom P, Rubio C, Lindblom A (1998) The role of ataxia-telangiectasia heterozygotes in familial breast cancer. Cancer Res 58(7):1376–1379

    CAS  PubMed  Google Scholar 

  14. Tavtigian SV, Oefner PJ, Babikyan D, Hartmann A, Healey S, Le Calvez-Kelm F, Lesueur F, Byrnes GB, Chuang SC, Forey N, Feuchtinger C, Gioia L, Hall J, Hashibe M, Herte B, McKay-Chopin S, Thomas A, Vallée MP, Voegele C, Webb PM, Whiteman DC, Australian Cancer Study, Breast Cancer Family Registries (BCFR), Kathleen Cuningham Foundation Consortium for Research into Familial Aspects of Breast Cancer (kConFab), Sangrajrang S, Hopper JL, Southey MC, Andrulis IL, John EM, Chenevix-Trench G (2009) Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. Am J Hum Genet 85(4):427–446

    Article  CAS  PubMed  Google Scholar 

  15. Chenevix-Trench G, Spurdle AB, Gatei M, Kelly H, Marsh A, Chen X, Donn K, Cummings M, Nyholt D, Jenkins MA, Scott C, Pupo GM, Dörk T, Bendix R, Kirk J, Tucker K, McCredie MR, Hopper JL, Sambrook J, Mann GJ, Khanna KK (2002) Dominant negative ATM mutations in breast cancer families. J Natl Cancer Inst 94(3):205–215

    PubMed  Google Scholar 

  16. Broeks A, Urbanus JH, Floore AN, Dahler EC, Klijn JG, Rutgers EJ, Devilee P, Russell NS, van Leeuwen FE, van’t Veer LJ (2000) ATM-heterozygous germline mutations contribute to breast cancer-susceptibility. Am J Hum Genet 66(2):494–500

    Article  CAS  PubMed  Google Scholar 

  17. Dörk T, Bendix R, Bremer M, Rades D, Klöpper K, Nicke M, Skawran B, Hector A, Yamini P, Steinmann D, Weise S, Stuhrmann M, Karstens JH (2001) Spectrum of ATM gene mutations in a hospital-based series of unselected breast cancer patients. Cancer Res 61(20):7608–7615

    PubMed  Google Scholar 

  18. Lei H, Pospisilova D, Lindblom A, Vorechovsky I (2002) Re: dominant negative ATM mutations in breast cancer families. J Natl Cancer Inst 94(12):951–952

    PubMed  Google Scholar 

  19. Sommer SS, Buzin CH, Jung M, Zheng J, Liu Q, Jeong SJ, Moulds J, Nguyen VQ, Feng J, Bennett WP, Dritschilo A (2002) Elevated frequency of ATM gene missense mutations in breast cancer relative to ethnically matched controls. Cancer Genet Cytogenet 134(1):25–32

    Article  CAS  PubMed  Google Scholar 

  20. Bernstein JL, Bernstein L, Thompson WD, Lynch CF, Malone KE, Teitelbaum SL, Olsen JH, Anton-Culver H, Boice JD, Rosenstein BS, Borresen-Dale AL, Gatti RA, Concannon P, Haile RW (2003) ATM variants 7271T>G and IVS10-6T>G among women with unilateral and bilateral breast cancer. Br J Cancer 89(8):1513–1516

    Article  CAS  PubMed  Google Scholar 

  21. Broeks A, Urbanus JH, de Knijff P, Devilee P, Nicke M, Klöpper K, Dörk T, Floore AN, van’t Veer LJ (2003) IVS10-6T>G, an ancient ATM germline mutation linked with breast cancer. Hum Mutat 21(5):521–528

    Article  CAS  PubMed  Google Scholar 

  22. Lindeman GJ, Hiew M, Visvader JE, Leary J, Field M, Gaff CL, Gardner RJ, Trainor K, Cheetham G, Suthers G, Kirk J (2004) Frequency of the ATM IVS10-6T>G variant in Australian multiple-case breast cancer families. Breast Cancer Res 6(4):401–407

    Article  Google Scholar 

  23. Szabo CI, Schutte M, Broeks A, Houwing-Duistermaat JJ, Thorstenson YR, Durocher F, Oldenburg RA, Wasielewski M, Odefrey F, Thompson D, Floore AN, Kraan J, Klijn JG, van den Ouweland AM, Wagner TM, Devilee P, Simard J, van’t Veer LJ, Goldgar DE, Meijers-Heijboer H (2004) Are ATM mutations 7271T → G and IVS10–6T → G really high-risk breast cancer-susceptibility alleles? Cancer Res 64(3):840–843

    Article  CAS  PubMed  Google Scholar 

  24. Thompson D, Antoniou AC, Jenkins M, Marsh A, Chen X, Wayne T, Tesoriero A, Milne R, Spurdle A, Thorstenson Y, Southey M, Giles GG, Khanna KK, Sambrook J, Oefner P, Goldgar D, Hopper JL, Easton D, Chenevix-Trench G, KConFab Investigators (2005) Two ATM variants and breast cancer risk. Hum Mutat 25(6):594–595

    Article  PubMed  Google Scholar 

  25. Balleine RL, Murali R, Bilous AM, Farshid G, Waring P, Provan P, Byth K, Thorne H, kConFab Investigators, Kirk JA (2006) Histopathological features of breast cancer in carriers of ATM gene variants. Histopathology 49(5):523–532

    Article  CAS  PubMed  Google Scholar 

  26. Bernstein JL, Teraoka S, Southey MC, Jenkins MA, Andrulis IL, Knight JA, John EM, Lapinski R, Wolitzer AL, Whittemore AS, West D, Seminara D, Olson ER, Spurdle AB, Chenevix-Trench G, Giles GG, Hopper JL, Concannon P (2006) Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the breast cancer family registry. Hum Mutat 27(11):1122–1128

    Article  CAS  PubMed  Google Scholar 

  27. Soukupova J, Dundr P, Kleibl Z, Pohlreich P (2008) Contribution of mutations in ATM to breast cancer development in the Czech population. Oncol Rep 19(6):1505–1510

    CAS  PubMed  Google Scholar 

  28. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10(1):101–129

    Article  Google Scholar 

  29. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748

    CAS  PubMed  Google Scholar 

  30. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  31. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    CAS  PubMed  Google Scholar 

  32. Martin A-M, Weber BL (2000) Genetic and hormonal risk factors in breast cancer. J Natl Cancer Inst (Bethesda) 92(14):1126–1135

    Article  CAS  Google Scholar 

  33. Goss PE, Sierra S (1998) Current perspectives on radiation-induced breast cancer. J Clin Oncol 16(1):338–347

    CAS  PubMed  Google Scholar 

  34. Nathanson KN, Wooster R, Weber BL (2001) Breast cancer genetics: what we know and what we need. Nat Med 7(5):552–556

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

This study was supported by Guangdong province “211” project (Grant No. 201004).

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Authors and Affiliations

  1. Longgang Center for Disease Control and Prevention of Shenzhen, Shenzhen, China

    Hong Ding, Shui-Ming Li, Qu Liu & Lin Lin

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

    Chen Mao & Qing Chen

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  1. Hong Ding
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Correspondence to Qing Chen.

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Ding, H., Mao, C., Li, SM. et al. Lack of association between ATM C.1066-6T > G mutation and breast cancer risk: a meta-analysis of 8,831 cases and 4,957 controls. Breast Cancer Res Treat 125, 473–477 (2011). https://doi.org/10.1007/s10549-010-0977-x

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  • DOI: https://doi.org/10.1007/s10549-010-0977-x

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