Abstract
Genetic polymorphisms of p53 and its negative regulator murine double minute 2 homolog (MDM2) have been shown to be closely associated with tumorigenesis in a variety of human cancers. In the present study, single nucleotide polymorphism (SNP) at p53 codon 72 and MDM2 promoter 309 was examined for germline DNA samples from 102 endometrial cancer cases and 95 controls using polymerase chain reaction-based fragment analysis. There were no significant differences in the genotype and allele prevalence between control subjects and endometrial cancer patients for p53 codon 72. The GG genotype frequency of MDM2-SNP309 was statistically higher in endometrial cancer patients than that in normal healthy women when compared with the TG genotype (P = 0.0088). However, no statistically significant differences were found between the TT and TG or GG genotype frequencies and allele prevalence. Interestingly, the combination of the homozygous Arg/Arg genotype of p53 codon 72 and homozygous GG genotype of MDM2 SNP309 polymorphisms was significantly associated with the risk of endometrial cancer (odds ratio = 3.28, 95% confidence interval = 1.13 to 9.53, P = 0.0212). The homozygous variants of wild p53 codon 72 and mutant MDM2 promoter 309 may cooperatively increase the risk of endometrial cancer in a Japanese population.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Tsigris C, Chatzitheofylaktou A, Xiromeritis C et al. Genetic association studies in digestive system malignancies. Anticancer Res 2007; 27: 3577–87.
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.
Ueda M, Toji E, Nunobiki O et al. Germline polymorphism of cancer susceptibility genes in gynecologic cancer. Hum Cell 2008; 21: 95–104.
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.
Woods DB, Vousden KH. Regulation of p53 function. Exp Cell Res 2001; 264: 56–66.
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.
Ara S, Lee PS, Hansen MF, Saya H. Codon 72 polymorphism of the TP53 gene. Nucleic Acids Res 1990; 18: 4961.
Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature 1997; 387: 299–303.
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.
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.
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.
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.
Buchynska LG, Nesina IP, Kashuba EV. Different trends of p53, MDM2 and p14 ARF expression patterns in endometrial adenocarcinomas versus hyperplasia. Exp Oncol 2007; 29: 287–94.
Horrée N, an Diest PJ, van der Groep P, Sie-Go DM, Heintz AP. Progressive derailment of cell cycle regulators in endometrial carcinogenesis. J Clin Pathol 2008; 61: 36–42.
Walsh CS, Miller CW, Karlan BY, Koeffler HP. Association between a functional single nucleotide polymorphism in the MDM2 gene and sporadic endometrial cancer risk. Gynecol Oncol 2007; 104: 660–4.
Terry K, McGrath M, Lee IM, Buring J, De Vivo I. MDM2 SNP309 is associated with endometrial cancer risk. Cancer Epidemiol Biomarkers Prev 2008; 17: 983–6.
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.
Matlashewski GJ, Tuck S, Pim D, Lamb P, Schneider J, Crawford LV. Primary structure polymorphism at amino acid residue 72 of human p53. Mol Cell Biol 1987; 7: 961–3.
Roh JW, Kim JW, Park NH et al. p53 and p21 genetic polymorphisms and susceptibility to endometrial cancer. Gynecol Oncol 2004; 93: 499–505.
Esteller M, Garcia A, Martinez-Palones JM, Xercavins J, Reventos J. Susceptibility to endometrial cancer: influence of allelism at p53, glutathione S-transferase (GSTM1 and GSTT1) and cytochrome P-450 (CYP1A1) loci. Br J Cancer 1997; 75: 1385–8.
Peller S, Halperin R, Schneider D, Kopilova Y, Rotter V. Polymorphisms of the p53 gene in women with ovarian or endometrial carcinoma. Oncol Rep 1999; 6: 193–7.
Agorastos T, Masouridou S, Lambropoulos AF et al. P53 codon 72 polymorphism and correlation with ovarian and endometrial cancer in Greek women. Eur J Cancer Prev 2004; 13: 277–80.
Ashton KA, Proietto A, Otton G et al. Polymorphisms in TP53 and MDM2 combined are associated with high grade endometrial cancer. Gynecol Oncol 2009; 113: 109–14.
Boersma BJ, Howe TM, Goodman JE et al. Association of breast cancer outcome with status of p53 and MDM2 SNP309. J Natl Cancer Inst 2006; 98: 911–19.
Schmidt MK, Reincke S, Broeks A et al. Do MDM2 SNP309 and TP53 R72P interact in breast cancer susceptibility? A large pooled series from the breast cancer association consortium. Cancer Res 2007; 67: 9584–90.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nunobiki, O., Ueda, M., Yamamoto, M. et al. Polymorphisms of p53 codon 72 and MDM2 promoter 309 and the risk of endometrial cancer. Hum Cell 22, 101–106 (2009). https://doi.org/10.1111/j.1749-0774.2009.00075.x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1111/j.1749-0774.2009.00075.x