期刊
CLINICAL CANCER RESEARCH
卷 11, 期 19, 页码 6840-6844出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-05-1139
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- NCI NIH HHS [CA67941, CA16058] Funding Source: Medline
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 polymorphisms on age of onset in Lynch syndrome and of the p53 polymorphism both 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 x(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.
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