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No significant association between the TP53 codon 72 polymorphism and breast cancer risk: a meta-analysis of 21 studies involving 24,063 subjects

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

Abstract

Conflicting data have been published as to the possible association between polymorphism in codon 72 of the TP53 tumor suppressor gene and the risk of developing breast cancer. In order to address this question, we carried out a meta-analysis of 21 studies of and this polymorphism and breast cancer risk, which collectively included 12,601 cases and 11,462 controls. Studies were identified by searching the Medline, PubMed, Embase, and ISI Web of Knowledge databases. The strength of association between the TP53 codon 72 polymorphism and breast cancer risk was assessed by calculating crude OR values with 95% CIs, with pooled OR values calculated separately for three genetic inheritance models. We found no significant association between TP53 codon 72 polymorphism and breast cancer risk for either the codominant inheritance model (Pro/Arg vs. Pro/Pro: OR = 1.063, 95% CI = 0.967–1.169; Arg/Arg vs. Pro/Pro: OR = 1.245, 95% CI = 0.997–1.554), the dominant model (OR = 1.146, 95% CI = 0.979–1.340), or the recessive model (OR = 1.179, 95% CI = 1.020–1.362). Stratified analysis by ethnicity and source of controls similarly revealed no significant association for any of the genetic models. In summary, this meta-analysis provides strong evidence that the TP53 codon 72 polymorphism is not associated with the risk of developing breast cancer.

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References

  1. Berns EM, van Staveren IL, Look MP, Smid M, Klijn JGM, Foekens JA (1998) Mutations in residues of TP53 that directly contact DNA predict poor outcome in human primary breast cancer. Br J Cancer 77:1130–1136

    CAS  PubMed  Google Scholar 

  2. Goldhirsch A (2000) Breast cancer. In: Cavalli F, Hansen H, Kaye SB (eds) Textbook of medical oncology. Martin Dunitz, London, pp 137–183

    Google Scholar 

  3. Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P et al (1989) Mutations in the p53 gene occur in diverse human tumour types. Nature 342:705–708

    Article  CAS  PubMed  Google Scholar 

  4. Oren M (2003) Decision making by p53: life, death and cancer. Cell Death 10:431–442

    Article  CAS  Google Scholar 

  5. Donehower LA (2005) p53 guardian and suppressor of longevity? Exp Gerontol 40:7–9

    Article  CAS  PubMed  Google Scholar 

  6. Wang-Gohrke S, Rebbeck TR, Besenfelder W, Kreienberg R, Runnebaum IB (1998) p53 germline polymorphisms are associated with an increased risk for breast cancer in German women. Anticancer Res 18:2095–2099

    CAS  PubMed  Google Scholar 

  7. Papadakis EN, Dokianakis DN, Spandidos DA (2000) p53 codon 72 polymorphisms as a risk factor in the development of breast cancer. Mol Cell Bio Res Comm 3:389–392

    Article  CAS  Google Scholar 

  8. Kalemi TG, Lambropoulos AF, Gueorguiev M, Chrisafi S, Papazisis KT, Kotsis A (2005) The association of p53 mutations and p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms with breast cancer in Northern Greece. Cancer Lett 222:57–65

    Article  CAS  PubMed  Google Scholar 

  9. Själander A, Birgander R, Hallmans G, Cajander S, Lenner P, Athlin L, Beckman G, Beckman L (1996) p53 polymorphisms and haplotypes in breast cancer. Carcinogenesis 17:1313–1316

    Article  PubMed  Google Scholar 

  10. Akkiprik M, Sonmez O, Gulluoglu BM, Caglar HB, Kaya H, Demirkalem P, Abacioglu U, Sengoz M, Sav A, Ozer A (2009) Analysis of p53 gene polymorphisms and protein over-expression in patients with breast cancer. Pathol Oncol Res 15:359–368

    Article  CAS  PubMed  Google Scholar 

  11. Damin AP, Frazzon AP, Damin DC, Roehe A, Hermes V, Zettler C, Alexandre CO (2006) Evidence for an association of TP53 codon 72 polymorphism with breast cancer risk. Cancer Detect Prev 30:523–529

    Article  CAS  PubMed  Google Scholar 

  12. Aoki MN, da Silva AHAC, Amarante MK, do Val Carneiro JL, Fungaro MH, Watanabe MA (2009) CCR5 and p53 codon 72 gene polymorphisms: implications in breast cancer development. Int J Mol Med 23:429–435

    CAS  PubMed  Google Scholar 

  13. Baynes C, Healey CS, Pooley KA, Scollen S, Luben RN, Thompson DJ, Pharoah PD, Easton DF, Ponder BA, Dunning AM (2007) SEARCH breast cancer study: common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk. Breast Cancer Res 9(2):R27

    Article  PubMed  Google Scholar 

  14. Buyru N, Tigli H, Dalay N (2003) P53 codon 72 polymorphism in breast cancer. Oncol Rep 10:711–714

    CAS  PubMed  Google Scholar 

  15. Gochhait S, Bukhari SI, Bairwa N, Vadhera S, Darvishi K, Raish M, Gupta P, Husain SA, Bamezai RN (2007) Implication of BRCA2–26G>A 5′ untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by p53 codon 72 Arg>Pro polymorphism. Breast Cancer Res 9:R71

    Article  PubMed  Google Scholar 

  16. Henríquez-Hernández LA, Murias-Rosales A, Hernández GA, Cabrera DLA, Díaz-Chico BN, Mori DSM, Fernández PL (2009) Gene polymorphisms in TYMS, MTHFR, p53 and MDR1 as risk factors for breast cancer: a case-control study. Oncol Rep 22:1425–1433

    Article  PubMed  Google Scholar 

  17. Huang XE, Hamajima N, Katsuda N, Matsuo K, Hirose K, Mizutani M, Iwata H, Miura S, Xiang J, Tokudome S, Tajima K (2003) Association of p53 codon Arg72Pro and p73 G4C14-to-A4T14 at exon 2 genetic polymorphisms with the risk of Japanese breast cancer. Breast Cancer 10:307–311

    Article  PubMed  Google Scholar 

  18. Katiyar S, Thelma BK, Murthy NS, Hedau S, Jain N, Gopalkrishna V, Husain SA, Das BC (2003) Polymorphism of the p53 codon 72 Arg/Pro and the risk of HPV type 16/18-associated cervical and oral cancer in India. Mol Cell Biochem 252:117–124

    Article  CAS  PubMed  Google Scholar 

  19. Khadang B, Fattahi MJ, Talei A, Dehaghani AS, Ghaderi A (2007) Polymorphism of TP53 codon 72 showed no association with breast cancer in Iranian women. Cancer Genet Cytogenet 173:38–42

    Article  CAS  PubMed  Google Scholar 

  20. Li T, Lu ZM, Guo M, Wu QJ, Chen KN, Xing HP, Mei Q, Ke Y (2002) p53 codon 72 polymorphism (C/G) and the risk of human papillomavirus-associated carcinomas in China. Cancer 95:2571–2576

    Article  CAS  PubMed  Google Scholar 

  21. Mabrouk I, Baccouche S, El-Abed R, Mokdad-Gargouri R, Mosbah A, Saïd S, Daoud J, Frikha M, Jlidi R, Gargouri A (2003) No evidence of correlation between p53 codon 72 polymorphism and risk of bladder or breast carcinoma in Tunisian patients. Ann N Y Acad Sci 1010:764–770

    Article  CAS  PubMed  Google Scholar 

  22. Schmidt MK, Reincke S, Broeks A, Braaf LM, Hogervorst FB, Tollenaar RA, Johnson N, Fletcher O, Peto J, Tommiska J, Blomqvist C, Nevanlinna HA, Healey CS, Dunning AM, Pharoah PD, Easton DF, Dörk T, Van’t Veer LJ (2007) Breast cancer association consortium: do MDM2 SNP309 and TP53 R72P interact in breast cancer susceptibility? A large pooled series from the breast cancer association consortium. Cancer Res 67:9584–9590

    Article  CAS  PubMed  Google Scholar 

  23. Sprague BL, Trentham-Dietz A, Garcia-Closas M, Newcomb PA, Titus-Ernstoff L, Hampton JM, Chanock SJ, Haines JL, Egan KM (2007) Genetic variation in TP53 and risk of breast cancer in a population-based case control study. Carcinogenesis 28:1680–1686

    Article  CAS  PubMed  Google Scholar 

  24. Tommiska J, Eerola H, Heinonen M, Salonen L, Kaare M, Tallila J, Ristimäki A, von Smitten K, Aittomäki K, Heikkilä P, Blomqvist C, Nevanlinna H (2005) Breast cancer patients with p53 Pro72 homozygous genotype have a poorer survival. Clin Cancer Res 11:5098–5103

    Article  CAS  PubMed  Google Scholar 

  25. Wang-Gohrke S, Becher H, Kreienberg R, Runnebaum IB, Chang-Claude J (2003) Intron 3 16 bp duplication polymorphism of p53 is associated with an increased risk for breast cancer by the age of 50 years. Pharmacogenetics 12:269–272

    Article  Google Scholar 

  26. Weston A, Pan CF, Ksieski HB, Wallenstein S, Berkowitz GS, Tartter PI, Bleiweiss IJ, Brower ST, Senie RT, Wolff MS (1997) p53 haplotype determination in breast cancer. Cancer Epidemiol Biomarkers Prev 6:105–112

    CAS  PubMed  Google Scholar 

  27. Zhang W, Jin MJ, Chen K (2007) Association of p53 polymorphisms and its haplotypes with susceptibility of breast cancer. Zhejiang Da Xue Xue Bao Yi Xue Ban 36:561–566

    CAS  PubMed  Google Scholar 

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

    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 22:719–748

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  32. 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 

  33. Qiu LX, Yao L, Mao C, Yu KD, Zhan P, Chen B, Yuan H, Zhang J, Xue K, Hu XC (2010) Lack of association of CYP1A2-164 A/C polymorphism with breast cancer susceptibility: a meta-analysis involving 17,600 subjects. Breast Cancer Res Treat. doi:10.1007/s10549-009-0731-4

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Conflicts of interest

None of the authors of this study has any applicable conflict of interest.

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Authors and Affiliations

  1. Evidence-Based Medicine Group, Department of Surgery, The Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China

    Yanlei Ma, Jianjun Yang, Zhihua Liu, Peng Zhang, Zhe Yang, Yu Wang & Huanlong Qin

  2. Department of Surgery, The Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, 600 Yishan Road, Shanghai, 200233, People’s Republic of China

    Yanlei Ma, Jianjun Yang, Peng Zhang, Zhe Yang & Huanlong Qin

Authors
  1. Yanlei Ma
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  2. Jianjun Yang
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  3. Zhihua Liu
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  4. Peng Zhang
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  5. Zhe Yang
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  6. Yu Wang
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  7. Huanlong Qin
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Corresponding authors

Correspondence to Zhe Yang, Yu Wang or Huanlong Qin.

Additional information

Y. Ma and J. Yang are equally contributed to this study.

Z. Yang, Y. Wang, and H. Qin are the co-corresponding author for this article.

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Ma, Y., Yang, J., Liu, Z. et al. No significant association between the TP53 codon 72 polymorphism and breast cancer risk: a meta-analysis of 21 studies involving 24,063 subjects. Breast Cancer Res Treat 125, 201–205 (2011). https://doi.org/10.1007/s10549-010-0920-1

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  • DOI: https://doi.org/10.1007/s10549-010-0920-1

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