DOI: 10.1158/1078-0432.ccr-05-1139. <i>p53</i> Codon 72 and <i>MDM2</i> SNP309 Polymorphisms and Age of Colorectal Cancer Onset in Lynch Syndrome

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

10.1158/1078-0432.ccr-05-1139

Crossref journal-article

American Association for Cancer Research (AACR)

Clinical Cancer Research (1086)

Abstract

Abstract 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 χ2 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.

Bibliography

Sotamaa, K., Liyanarachchi, S., Mecklin, J.-P., JaÌrvinen, H., Aaltonen, L. A., PeltomaÌki, P., & de la Chapelle, A. (2005). p53 Codon 72 and MDM2 SNP309 Polymorphisms and Age of Colorectal Cancer Onset in Lynch Syndrome. Clinical Cancer Research, 11(19), 6840â6844.

Authors 7

Kaisa Sotamaa (first)
Sandya Liyanarachchi (additional)
Jukka-Pekka Mecklin (additional)
Heikki Järvinen (additional)
Lauri A. Aaltonen (additional)
Päivi Peltomäki (additional)
Albert de la Chapelle (additional)

References 28 Referenced 69

Dates

Type	When
Created	19 years, 5 months ago (March 21, 2006, 1:43 p.m.)
Deposited	3 years, 2 months ago (June 11, 2022, 3:19 p.m.)
Indexed	1 year, 9 months ago (Nov. 21, 2023, 2:41 p.m.)
Issued	19 years, 10 months ago (Oct. 1, 2005)
Published	19 years, 10 months ago (Oct. 1, 2005)
Published Online	19 years, 10 months ago (Oct. 3, 2005)
Published Print	19 years, 10 months ago (Oct. 1, 2005)

Funders 0

None

BibTeX

@article{Sotamaa_2005, title={p53 Codon 72 and MDM2 SNP309 Polymorphisms and Age of Colorectal Cancer Onset in Lynch Syndrome}, volume={11}, ISSN={1557-3265}, url={http://dx.doi.org/10.1158/1078-0432.ccr-05-1139}, DOI={10.1158/1078-0432.ccr-05-1139}, number={19}, journal={Clinical Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Sotamaa, Kaisa and Liyanarachchi, Sandya and Mecklin, Jukka-Pekka and Järvinen, Heikki and Aaltonen, Lauri A. and Peltomäki, Päivi and de la Chapelle, Albert}, year={2005}, month=oct, pages={6840–6844} }

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  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>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.</jats:p>\n               <jats:p>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 \u03c72 test, Kaplan-Meier statistics, and Cox regression model to analyze the data.</jats:p>\n               <jats:p>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.</jats:p>\n               <jats:p>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.</jats:p>",
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