This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sotamaa, K. Articles by de la Chapelle, A. Search for Related Content PubMed PubMed Citation Articles by Sotamaa, K. Articles by de la Chapelle, A.

p53 Codon 72 and MDM2 SNP309 Polymorphisms and Age of Colorectal Cancer Onset in Lynch Syndrome

Authors' Affiliations: ¹ Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio; ² Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland; ³ Department of Surgery, Helsinki University Central Hospital; and ⁴ Department of Medical Genetics, University of Helsinki, Helsinki, Finland

Requests for reprints: Albert de la Chapelle, Human Cancer Genetics, 646 Tzagournis Medical Research Facility, 420 West 12th Avenue, Columbus, OH 43210. Phone: 614-688-4781; Fax: 1-614-688-4772; E-mail: delachapelle-1{at}medctr.osu.edu.

Purpose: The Arg/Pro polymorphism in codon 72 of p53 was recently associated with age of onset of colorectal cancer in Lynch syndrome. A novel polymorphism in the promoter region of MDM2 was associated with age of cancer onset in Li-Fraumeni syndrome. We studied the influence of both polymorphisms on age of onset in Lynch syndrome and of the p53 polymorphism also in sporadic colorectal cancer.

Experimental Design: We genotyped p53 codon 72 in 193 individuals with Lynch syndrome mutations, 93 patients with sporadic microsatellite unstable colorectal cancer, and 93 patients with sporadic microsatellite stable colorectal cancer from Finland and 323 Finnish controls. We genotyped 30 colorectal cancer patients with Lynch syndrome mutations from Ohio and 118 U.S. controls. We genotyped SNP309 of MDM2 in the Lynch syndrome groups. We used ² test, Kaplan-Meier statistics, and Cox regression model to analyze the data.

Results: Allele frequencies of both polymorphisms were similar in subjects and controls from both populations and showed Hardy-Weinberg equilibrium. Neither polymorphism was associated with age of colorectal cancer onset in any of the subject groups.

Conclusions: This study failed to show any role of the p53 polymorphism on age of colorectal cancer onset in Lynch syndrome and sporadic colorectal cancer. The polymorphism in the MDM2 promoter had no affect on age of onset in Lynch syndrome. Accurate information about age of onset is important in clinical practice, especially in high-risk conditions. As association studies are vulnerable to biologically insignificant variation, both positive and negative findings need to be reported to enable unbiased assessment of the significance of putative risk variants.

This article has been cited by other articles:

				S. Cattelani, R. Defferrari, S. Marsilio, R. Bussolari, O. Candini, F. Corradini, G. Ferrari-Amorotti, C. Guerzoni, L. Pecorari, C. Menin, et al. Impact of a Single Nucleotide Polymorphism in the MDM2 Gene on Neuroblastoma Development and Aggressiveness: Results of a Pilot Study on 239 Patients Clin. Cancer Res., June 1, 2008; 14(11): 3248 - 3253. [Abstract] [Full Text] [PDF]

				S. Wilkening, J. L. Bermejo, and K. Hemminki MDM2 SNP309 and cancer risk: a combined analysis Carcinogenesis, November 1, 2007; 28(11): 2262 - 2267. [Abstract] [Full Text] [PDF]

				M. K. Schmidt, S. Reincke, A. Broeks, L. M. Braaf, F. B.L. Hogervorst, R. A.E.M. Tollenaar, N. Johnson, O. Fletcher, J. Peto, J. Tommiska, 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., October 1, 2007; 67(19): 9584 - 9590. [Abstract] [Full Text] [PDF]

				H. Hirata, Y. Hinoda, N. Kikuno, K. Kawamoto, Y. Suehiro, Y. Tanaka, and R. Dahiya MDM2 SNP309 Polymorphism as Risk Factor for Susceptibility and Poor Prognosis in Renal Cell Carcinoma Clin. Cancer Res., July 15, 2007; 13(14): 4123 - 4129. [Abstract] [Full Text] [PDF]

				P. T. Campbell, L. Edwards, J. R. McLaughlin, J. Green, H. B. Younghusband, and M. O. Woods Cytochrome P450 17A1 and Catechol O-Methyltransferase Polymorphisms and Age at Lynch Syndrome Colon Cancer Onset in Newfoundland Clin. Cancer Res., July 1, 2007; 13(13): 3783 - 3788. [Abstract] [Full Text] [PDF]

				M. Sanchez-Carbayo, N. D. Socci, T. Kirchoff, N. Erill, K. Offit, B. H. Bochner, and C. Cordon-Cardo A Polymorphism in HDM2 (SNP309) Associates with Early Onset in Superficial Tumors, TP53 Mutations, and Poor Outcome in Invasive Bladder Cancer Clin. Cancer Res., June 1, 2007; 13(11): 3215 - 3220. [Abstract] [Full Text] [PDF]

				G. Zhou, Y. Zhai, Y. Cui, X. Zhang, X. Dong, H. Yang, Y. He, K. Yao, H. Zhang, L. Zhi, et al. MDM2 Promoter SNP309 Is Associated with Risk of Occurrence and Advanced Lymph Node Metastasis of Nasopharyngeal Carcinoma in Chinese Population Clin. Cancer Res., May 1, 2007; 13(9): 2627 - 2633. [Abstract] [Full Text] [PDF]

				U. Tabori, S. Nanda, H. Druker, J. Lees, and D. Malkin Younger Age of Cancer Initiation Is Associated with Shorter Telomere Length in Li-Fraumeni Syndrome Cancer Res., February 15, 2007; 67(4): 1415 - 1418. [Abstract] [Full Text] [PDF]

				H. Alazzouzi, G. Suriano, A. Guerra, A. Plaja, E. Espin, M. Armengol, P. Alhopuro, S. Velho, Y. Shinomura, J. J. Gonzalez-Aguilera, et al. Tumour selection advantage of non-dominant negative P53 mutations in homozygotic MDM2-SNP309 colorectal cancer cells J. Med. Genet., January 1, 2007; 44(1): 75 - 80. [Abstract] [Full Text] [PDF]

				S. Wilkening, J. L. Bermejo, B. Burwinkel, R. Klaes, C. R. Bartram, A. Meindl, P. Bugert, R. K. Schmutzler, B. Wappenschmidt, M. Untch, et al. The Single Nucleotide Polymorphism IVS1+309 in Mouse Double Minute 2 Does Not Affect Risk of Familial Breast Cancer Cancer Res., January 15, 2006; 66(2): 646 - 648. [Abstract] [Full Text] [PDF]