p53 Polymorphism and Age of Onset of Hereditary Nonpolyposis Colorectal Cancer in a Caucasian Population
| Autor: | Christopher I. Amos, Xuedong Chi, Patrick M. Lynch, J. Shawn Jones, Marsha L. Frazier, Xiangjun Gu |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty DNA Repair Genotype Colorectal cancer DNA Mutational Analysis Polymerase Chain Reaction White People Risk Factors Proto-Oncogene Proteins Internal medicine Genetic predisposition medicine Humans Genetic variability Age of Onset Allele Polymorphism Single-Stranded Conformational Survival analysis Adaptor Proteins Signal Transducing Aged Aged 80 and over Genetics Polymorphism Genetic business.industry Nuclear Proteins DNA Neoplasm Middle Aged Genes p53 medicine.disease Colorectal Neoplasms Hereditary Nonpolyposis Neoplasm Proteins DNA-Binding Proteins Genetics Population MutS Homolog 2 Protein Mutation Female DNA mismatch repair Age of onset Carrier Proteins MutL Protein Homolog 1 business |
| Zdroj: | Clinical Cancer Research. 10:5845-5849 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome of familial malignancies. Colorectal and endometrial cancers are most frequently observed. The syndrome results mainly from germ-line mutations in DNA mismatch repair genes. A common G-to-C polymorphism at codon 72 in the p53 gene has been associated with increased risk for lung, nasopharyngeal, oral, prostate, and breast cancers and may be a marker for genetic susceptibility to colorectal cancer. We studied the influence of this p53 polymorphism on HNPCC age of onset. Experimental Design: We determined the p53 genotype of 92 Caucasian mismatch repair mutation carriers, of which, 47 had colorectal cancer. The subjects were genotyped by single-strand conformational polymorphism analysis. We tested the association between age of onset and the p53 genotypes by comparing Kaplan-Meier survival curves, evaluating the homogeneity of the curves using the log-rank test and Wilcoxon’s test, and estimating the association using the Cox proportional hazards regression model to adjust for potential demographic confounding factors. Results: The HNPCC patients who were heterozygous developed their colorectal cancer 13 years earlier than HNPCC patients who were homozygous for the wild-type allele. Conclusions: Combining knowledge of an individual’s p53 genotype with information on other genetic and environmental risk factors may improve risk estimates and help to identify individuals who are genetically susceptible to developing HNPCC at an earlier age. |
| Databáze: | OpenAIRE |
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