Skip to main content

Advertisement

SpringerLink
Log in

Murine double-minute 2 homolog single nucleotide polymorphism 309 and the risk of gynecologic cancer

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

A functional T to G germline polymorphism in the promoter region of murine double-minute 2 homolog single nucleotide polymorphism 309 (MDM2-SNP309) has been reported to profoundly accelerate tumor formation, suggesting that it may also represent a powerful cancer predisposing allele. In this study, MDM2-SNP309 was examined in a total of 400 blood samples from 108 normal, 88 cervical, 119 endometrial and 85 ovarian cancer cases using two independent polymerase chain reaction assays for each allele. When the MDM2-SNP309 genotype was classified into two subgroups of TT+TG and GG, the GG genotype was associated with an increased risk for the development of endometrial cancer (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.05 to 3.47) compared with the TT+TG genotype (P = 0.0353). The G allele also increased the risk of endometrial cancer (OR = 1.20, 95% CI = 0.83 to 1.74) compared with the T allele, but no statistical difference was found (P = 0.3333). The homozygous GG genotype was also associated with postmenopausal status and type I endometrial cancer (P = 0.0306 and 0.0326, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and cervical or ovarian cancer patients. These results suggest that homozygous GG genotype of MDM2-SNP309 may be a risk factor for postmenopausal and type I endometrial cancer in a Japanese population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Tsigris C, Chatzitheofylaktou A, Xiromeritis C et al. Genetic association studies in digestive system malignancies. Anticancer Res 2007; 27: 3577–87.

    PubMed  CAS  Google Scholar 

  2. Ueda M, Hung YC, Terai Y et al. Glutathione S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in human tumor cells. Hum Cell 2003; 16: 241–51.

    Article  PubMed  Google Scholar 

  3. Ueda M, Toji E, Nunobiki O et al. Germline polymorphism of cancer susceptibility genes in gynecologic cancer. Hum Cell 2008; 21: 95–104.

    Article  PubMed  Google Scholar 

  4. Dulic V, Kaufmann WK, Wilson SJ et al. p53 dependent inhibition of cyclin-dependent kinase activities in human fibroblast during radiation-induced G1 arrest. Cell 1994; 76: 1013–23.

    Article  PubMed  CAS  Google Scholar 

  5. Woods DB, Vousden KH. Regulation of p53 function. Exp Cell Res 2001; 264: 56–66.

    Article  PubMed  CAS  Google Scholar 

  6. Greenblatt MS, Bennett WP, Hollstein M et al. Mutations in the p53 gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 1994; 55: 4855–78.

    Google Scholar 

  7. Chen J, Wu X, Lin J et al. mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein. Mol. Cell. Biol. 1996; 16: 2445–52.

    PubMed  CAS  Google Scholar 

  8. Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature 1997; 387: 299–303.

    Article  PubMed  CAS  Google Scholar 

  9. Rayburn E, Zhang R, He J et al. MDM2 and human malignancies: expression, clinical pathology, prognostic markers, and implications for chemotherapy. Curr Cancer Drug Targets 2005; 5: 27–41.

    Article  PubMed  CAS  Google Scholar 

  10. Bond GL, Hu W, Bond EE et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 2004; 119: 591–602.

    Article  PubMed  CAS  Google Scholar 

  11. Menin C, Scaini MC, De Salvo GL et al. Association between MDM2-SNP309 and age at colorectal cancer diagnosis according to p53 mutation status. J Natl Cancer Inst 2006; 98: 285–8.

    Article  PubMed  CAS  Google Scholar 

  12. Dharel N, Kato N, Muroyama R et al. MDM2 promoter SNP309 is associated with the risk of hepatocellular carcinoma in patients with chronic hepatitis C. Clin Cancer Res 2006; 12: 4867–71.

    Article  PubMed  CAS  Google Scholar 

  13. Lum SS, Chua HW, Li H et al. 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 2008; 29: 754–61.

    Article  PubMed  CAS  Google Scholar 

  14. Meissner Rde V, Barbosa RN, Fernandes JV et al. No association between SNP309 promoter polymorphism in the MDM2 and cervical cancer in a study from northeastern Brazil. Cancer Detect Prev 2007; 31: 371–4.

    Article  PubMed  CAS  Google Scholar 

  15. Walsh CS, Miller CW, Karlan BY et al. Association between a functional single nucleotide polymorphism in the MDM2 gene and sporadic endometrial cancer risk. Gynecol Oncol 2007; 104: 660–4.

    Article  PubMed  CAS  Google Scholar 

  16. Terry K, McGrath M, Lee IM et al. MDM2 SNP309 is associated with endometrial cancer risk. Cancer Epidemiol. Biomarkers. Prev 2008; 17: 983–6.

    Article  PubMed  CAS  Google Scholar 

  17. Campbell IG, Eccles DM, Choong DY. No association of the MDM2 SNP309 polymorphism with risk of breast or ovarian cancer. Cancer Lett 2006; 240: 195–7.

    Article  PubMed  CAS  Google Scholar 

  18. Galic V, Willner J, Wollan M et al. Common polymorphisms in TP53 and MDM2 and the relationship to TP53 mutations and clinical outcomes in women with ovarian and peritoneal carcinomas. Genes Chromosomes Cancer 2007; 46: 239–47.

    Article  PubMed  CAS  Google Scholar 

  19. Bartel F, Jung J, Böhnke A et al. Both germ line and somatic genetics of the p53 pathway affect ovarian cancer incidence and survival. Clin Cancer Res 2008; 14: 89–96.

    Article  PubMed  CAS  Google Scholar 

  20. Yarden RI, Friedman E, Metsuyanim S et al. MDM2 SNP309 accelerates breast and ovarian carcinogenesis in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent. Breast Cancer Res Treat 2008; 111: 497–504.

    Article  PubMed  CAS  Google Scholar 

  21. Ueda M, Terai Y, Kanda K et al. Germline polymorphism of p53 codon 72 in gynecological cancer. Gynecol Oncol 2006; 100: 173–8.

    Article  PubMed  CAS  Google Scholar 

  22. Ueda M, Gemmill RM, West J et al. Mutations of the β- and γ-catenin genes are uncommon in human lung, breast, kidney, cervical and ovarian carcinomas. Br J Cancer 2001; 85: 64–8.

    Article  PubMed  CAS  Google Scholar 

  23. Bond GL, Hirshfield KM, Kirchhoff T et al. MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner. Cancer Res 2006; 66: 5104–10.

    Article  PubMed  CAS  Google Scholar 

  24. Lax SF. Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch 2004; 444: 213–23.

    Article  PubMed  CAS  Google Scholar 

  25. Honda T, Kato H, Imamura T et al. Involvement of p53 gene mutations in human endometrial carcinomas. Int. J. Cancer 1993; 53: 963–7.

    Article  PubMed  CAS  Google Scholar 

  26. Kihana T, Hamada K, Inoue Y et al. Mutation and allelic loss of the p53 gene in endometrial carcinoma. Incidence and outcome in 92 surgical patients. Cancer 1995; 76: 72–8.

    Article  PubMed  CAS  Google Scholar 

  27. Niwa K, Murase T, Morishita S et al. p53 overexpression and mutation in endometrial carcinoma: inverted relation with estrogen and progesterone receptor status. Cancer Detect Prev 1999; 23: 147–54.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cytopathology and Gynecology, Osaka Cancer Prevention and Detection Center, 1-6-107, Morinomiya, Joto-ku, 536-8588, Osaka, Japan

    Masatsugu Ueda, Michiko Yamamoto, Osamu Nunobiki, Eisaku Toji, Naomi Sato, Shinji Izuma, Yoshiaki Okamoto, Kiyo Torii & Sadamu Noda

Authors
  1. Masatsugu Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michiko Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Osamu Nunobiki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eisaku Toji
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naomi Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shinji Izuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoshiaki Okamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kiyo Torii
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sadamu Noda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masatsugu Ueda.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ueda, M., Yamamoto, M., Nunobiki, O. et al. Murine double-minute 2 homolog single nucleotide polymorphism 309 and the risk of gynecologic cancer. Hum Cell 22, 49–54 (2009). https://doi.org/10.1111/j.1749-0774.2009.00068.x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1111/j.1749-0774.2009.00068.x

Key words

Search

Navigation