Breast Cancer Research and Treatment

, Volume 120, Issue 2, pp 509–517

P53 codon 72 polymorphism contributes to breast cancer risk: a meta-analysis based on 39 case–control studies

  • Zhizhong Zhang
  • Meilin Wang
  • Dongmei Wu
  • Miaomiao Wang
  • Na Tong
  • Yuanyuan Tian
  • Zhengdong Zhang
Epidemiology

Abstract

P53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies revealing conflicting results on the role of p53 codon 72 polymorphism (G>C) on breast cancer risk led us to perform a meta-analysis to investigate this relationship. Thirty-nine published studies, including 26,041 breast cancer cases and 29,679 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results suggested that the variant genotypes were associated with a significantly reduced breast cancer risk (GC vs. GG: OR = 0.91, 95% CI: 0.83–1.00; CC/GC vs. GG: OR = 0.90, 95% CI: 0.82–0.99). In the stratified analyses, significantly decreased risks were also found among European populations (GC vs. GG: OR = 0.89, 95% CI: 0.80–0.99; CC/GC vs. GG: OR = 0.88, 95% CI: 0.80–0.98) and studies with population-based controls (GC vs. GG: OR = 0.88, 95% CI: 0.78–0.98; CC/GC vs. GG: OR = 0.87, 95% CI: 0.78–0.97). The results suggested that p53 codon 72 polymorphism may contribute to susceptibility to breast cancer, especially in Europeans. Additional well-designed large studies were required to validate this association in different populations.

Keywords

P53 Breast cancer Meta-analysis Molecular epidemiology Genetic variation 

Supplementary material

10549_2009_480_MOESM1_ESM.doc (90 kb)
Supplementary material 1 (DOC 89 kb)

References

  1. 1.
    Parkin DM, Bray F, Ferlay J et al (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156CrossRefPubMedGoogle Scholar
  2. 2.
    Yager JD, Davidson NE (2006) Estrogen carcinogenesis in breast cancer. N Engl J Med 354:270–282CrossRefPubMedGoogle Scholar
  3. 3.
    Veronesi U, Boyle P, Goldhirsch A et al (2005) Breast cancer. Lancet 365:1727–1741CrossRefPubMedGoogle Scholar
  4. 4.
    Bartkova J, Lukas J, Strauss M et al (1995) Cyclin D1 oncoprotein aberrantly accumulates in malignancies of diverse histogenesis. Oncogene 10:775–778PubMedGoogle Scholar
  5. 5.
    Porter-Jordan K, Lippman ME (1994) Overview of the biologic markers of breast cancer. Hematol Oncol Clin North Am 8:73–100PubMedGoogle Scholar
  6. 6.
    Callahan R, Cropp CS, Merlo GR et al (1992) Somatic mutations and human breast cancer. A status report. Cancer 69:1582–1588CrossRefPubMedGoogle Scholar
  7. 7.
    Hollstein M, Sidransky D, Vogelstein B et al (1991) p53 mutations in human cancers. Science 253:49–53CrossRefPubMedGoogle Scholar
  8. 8.
    Petitjean A, Achatz MI, Borresen-Dale AL et al (2007) TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene 26:2157–2165CrossRefPubMedGoogle Scholar
  9. 9.
    Harris N, Brill E, Shohat O et al (1986) Molecular basis for heterogeneity of the human p53 protein. Mol Cell Biol 6:4650–4656PubMedGoogle Scholar
  10. 10.
    Dumont P, Leu JI, Della Pietra ACIII et al (2003) The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 33:357–365CrossRefPubMedGoogle Scholar
  11. 11.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMedGoogle Scholar
  12. 12.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRefPubMedGoogle Scholar
  13. 13.
    Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedGoogle Scholar
  14. 14.
    Kawajiri K, Nakachi K, Imai K et al (1993) Germ line polymorphisms of p53 and CYP1A1 genes involved in human lung cancer. Carcinogenesis 14:1085–1089CrossRefPubMedGoogle Scholar
  15. 15.
    Sjalander A, Birgander R, Hallmans G et al (1996) p53 polymorphisms and haplotypes in breast cancer. Carcinogenesis 17:1313–1316CrossRefPubMedGoogle Scholar
  16. 16.
    Weston A, Pan CF, Ksieski HB et al (1997) p53 haplotype determination in breast cancer. Cancer Epidemiol Biomarkers Prev 6:105–112PubMedGoogle Scholar
  17. 17.
    Wang-Gohrke S, Rebbeck TR, Besenfelder W et al (1998) p53 germline polymorphisms are associated with an increased risk for breast cancer in German women. Anticancer Res 18:2095–2099PubMedGoogle Scholar
  18. 18.
    Khaliq S, Hameed A, Khaliq T et al (2000) P53 mutations, polymorphisms, and haplotypes in Pakistani ethnic groups and breast cancer patients. Genet Test 4:23–29CrossRefPubMedGoogle Scholar
  19. 19.
    Papadakis EN, Dokianakis DN, Spandidos DA (2000) p53 codon 72 polymorphism as a risk factor in the development of breast cancer. Mol Cell Biol Res Commun 3:389–392CrossRefPubMedGoogle Scholar
  20. 20.
    Li T, Lu ZM, Guo M et al (2002) p53 codon 72 polymorphism (C/G) and the risk of human papillomavirus-associated carcinomas in China. Cancer 95:2571–2576CrossRefPubMedGoogle Scholar
  21. 21.
    Wang-Gohrke S, Becher H, Kreienberg R et al (2002) Intron 3 16 bp duplication polymorphism of p53 is associated with an increased risk for breast cancer by the age of 50 years. Pharmacogenetics 12:269–272CrossRefPubMedGoogle Scholar
  22. 22.
    Buyru N, Tigli H, Dalay N (2003) P53 codon 72 polymorphism in breast cancer. Oncol Rep 10:711–714PubMedGoogle Scholar
  23. 23.
    Huang XE, Hamajima N, Katsuda N et al (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 10:307–311CrossRefPubMedGoogle Scholar
  24. 24.
    Mabrouk I, Baccouche S, El-Abed R et al (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 1010:764–770CrossRefPubMedGoogle Scholar
  25. 25.
    Suspitsin EN, Buslov KG, Grigoriev MY et al (2003) Evidence against involvement of p53 polymorphism in breast cancer predisposition. Int J Cancer 103:431–433CrossRefPubMedGoogle Scholar
  26. 26.
    Mahasneh AA, Abdel-Hafiz SS (2004) Polymorphism of p53 gene in Jordanian population and possible associations with breast cancer and lung adenocarcinoma. Saudi Med J 25:1568–1573PubMedGoogle Scholar
  27. 27.
    Noma C, Miyoshi Y, Taguchi T et al (2004) Association of p53 genetic polymorphism (Arg72Pro) with estrogen receptor positive breast cancer risk in Japanese women. Cancer Lett 210:197–203CrossRefPubMedGoogle Scholar
  28. 28.
    Kalemi TG, Lambropoulos AF, Gueorguiev M et al (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 222:57–65CrossRefPubMedGoogle Scholar
  29. 29.
    Ohayon T, Gershoni-Baruch R, Papa MZ et al (2005) The R72P P53 mutation is associated with familial breast cancer in Jewish women. Br J Cancer 92:1144–1148CrossRefPubMedGoogle Scholar
  30. 30.
    Siddique MM, Balram C, Fiszer-Maliszewska L et al (2005) Evidence for selective expression of the p53 codon 72 polymorphs: implications in cancer development. Cancer Epidemiol Biomarkers Prev 14:2245–2252CrossRefPubMedGoogle Scholar
  31. 31.
    Tommiska J, Eerola H, Heinonen M et al (2005) Breast cancer patients with p53 Pro72 homozygous genotype have a poorer survival. Clin Cancer Res 11:5098–5103CrossRefPubMedGoogle Scholar
  32. 32.
    Damin AP, Frazzon AP, Damin DC et al (2006) Evidence for an association of TP53 codon 72 polymorphism with breast cancer risk. Cancer Detect Prev 30:523–529CrossRefPubMedGoogle Scholar
  33. 33.
    Ma H, Hu Z, Zhai X et al (2006) Joint effects of single nucleotide polymorphisms in P53BP1 and p53 on breast cancer risk in a Chinese population. Carcinogenesis 27:766–771CrossRefPubMedGoogle Scholar
  34. 34.
    Baynes C, Healey CS, Pooley KA et al (2007) Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk. Breast Cancer Res 9:R27CrossRefPubMedGoogle Scholar
  35. 35.
    Buyru N, Altinisik J, Demokan S et al (2007) p53 genotypes and haplotypes associated with risk of breast cancer. Cancer Detect Prev 31:207–213CrossRefPubMedGoogle Scholar
  36. 36.
    Cox DG, Deer D, Guo Q et al (2007) The p53 Arg72Pro and MDM2-309 polymorphisms and risk of breast cancer in the nurses’ health studies. Cancer Causes Control 18:621–625CrossRefPubMedGoogle Scholar
  37. 37.
    Franekova M, Zubor P, Stanclova A et al (2007) Association of p53 polymorphisms with breast cancer: a case–control study in Slovak population. Neoplasma 54:155–161PubMedGoogle Scholar
  38. 38.
    Garcia-Closas M, Kristensen V, Langerod A et al (2007) Common genetic variation in TP53 and its flanking genes, WDR79 and ATP1B2, and susceptibility to breast cancer. Int J Cancer 121:2532–2538CrossRefPubMedGoogle Scholar
  39. 39.
    Gochhait S, Bukhari SI, Bairwa N et al (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:R71CrossRefPubMedGoogle Scholar
  40. 40.
    Johnson N, Fletcher O, Palles C et al (2007) Counting potentially functional variants in BRCA1, BRCA2 and ATM predicts breast cancer susceptibility. Hum Mol Genet 16:1051–1057CrossRefPubMedGoogle Scholar
  41. 41.
    Khadang B, Fattahi MJ, Talei A et al (2007) Polymorphism of TP53 codon 72 showed no association with breast cancer in Iranian women. Cancer Genet Cytogenet 173:38–42CrossRefPubMedGoogle Scholar
  42. 42.
    Pharoah PD, Tyrer J, Dunning AM et al (2007) Association between common variation in 120 candidate genes and breast cancer risk. PLoS Genet 3:e42CrossRefPubMedGoogle Scholar
  43. 43.
    Samson M, Swaminathan R, Rama R et al (2007) Role of GSTM1 (Null/Present), GSTP1 (Ile105Val) and P53 (Arg72Pro) genetic polymorphisms and the risk of breast cancer: a case control study from South India. Asian Pac J Cancer Prev 8:253–257PubMedGoogle Scholar
  44. 44.
    Schmidt MK, Reincke S, Broeks A et al (2007) Do MDM2 SNP309 and TP53 R72P interact in breast cancer susceptibility? A large pooled series from the breast cancer association consortium. Cancer Res 67:9584–9590CrossRefPubMedGoogle Scholar
  45. 45.
    Sprague BL, Trentham-Dietz A, Garcia-Closas M et al (2007) Genetic variation in TP53 and risk of breast cancer in a population-based case control study. Carcinogenesis 28:1680–1686CrossRefPubMedGoogle Scholar
  46. 46.
    Cavallone L, Arcand SL, Maugard C et al (2008) Haplotype analysis of TP53 polymorphisms, Arg72Pro and Ins16, in BRCA1 and BRCA2 mutation carriers of French Canadian descent. BMC Cancer 8:96CrossRefPubMedGoogle Scholar
  47. 47.
    Costa S, Pinto D, Pereira D et al (2008) Importance of TP53 codon 72 and intron 3 duplication 16 bp polymorphisms in prediction of susceptibility on breast cancer. BMC Cancer 8:32CrossRefPubMedGoogle Scholar
  48. 48.
    De Vecchi G, Verderio P, Pizzamiglio S et al (2008) The p53 Arg72Pro and Ins16 bp polymorphisms and their haplotypes are not associated with breast cancer risk in BRCA-mutation negative familial cases. Cancer Detect Prev 32:140–143CrossRefPubMedGoogle Scholar
  49. 49.
    Gaudet MM, Gammon MD, Bensen JT et al (2008) Genetic variation of TP53, polycyclic aromatic hydrocarbon-related exposures, and breast cancer risk among women on Long Island, New York. Breast Cancer Res Treat 108:93–99CrossRefPubMedGoogle Scholar
  50. 50.
    Lum SS, Chua HW, Li H et al (2008) MDM2 SNP309 G allele increases risk but the T allele is associated with earlier onset age of sporadic breast cancers in the Chinese population. Carcinogenesis 29:754–761CrossRefPubMedGoogle Scholar
  51. 51.
    Nordgard SH, Alnaes GI, Hihn B et al (2008) Pathway based analysis of SNPs with relevance to 5-FU therapy: relation to intratumoral mRNA expression and survival. Int J Cancer 123:577–585CrossRefPubMedGoogle Scholar
  52. 52.
    Singh V, Rastogi N, Mathur N et al (2008) Association of polymorphism in MDM-2 and p53 genes with breast cancer risk in Indian women. Ann Epidemiol 18:48–57CrossRefPubMedGoogle Scholar
  53. 53.
    Storey A, Thomas M, Kalita A et al (1998) Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 393:229–234CrossRefPubMedGoogle Scholar
  54. 54.
    Damin AP, Karam R, Zettler CG et al (2004) Evidence for an association of human papillomavirus and breast carcinomas. Breast Cancer Res Treat 84:131–137CrossRefPubMedGoogle Scholar
  55. 55.
    Akil N, Yasmeen A, Kassab A et al (2008) High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-1 expression: a tissue microarray study. Br J Cancer 99:404–407CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Zhizhong Zhang
    • 1
    • 2
  • Meilin Wang
    • 1
    • 2
  • Dongmei Wu
    • 2
  • Miaomiao Wang
    • 2
  • Na Tong
    • 3
  • Yuanyuan Tian
    • 2
  • Zhengdong Zhang
    • 1
    • 2
    • 3
  1. 1.Key Laboratory of Reproductive MedicineNanjing Medical UniversityNanjingChina
  2. 2.Department of Molecular & Genetic Toxicology, School of Public HealthNanjing Medical UniversityNanjingChina
  3. 3.Epidemiology & BiostatisticsCancer Center of Nanjing Medical UniversityNanjingChina

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