Somatic mutations, acetylator status, and prognosis in colorectal cancer
| Autor: | Alexander Dobrovic, R B Dymock, R. E. Sage, Jennifer E. Hardingham, David Roder, Ian C. Roberts-Thomson, W J Butler |
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| Rok vydání: | 1998 |
| Předmět: |
Oncology
medicine.medical_specialty Pathology Arylamine N-Acetyltransferase Colorectal cancer Rectum Biology Polymerase Chain Reaction Internal medicine medicine Carcinoma Humans Survival rate Genotyping Polymorphism Single-Stranded Conformational Neoplasm Staging Proportional Hazards Models Cancer Proportional hazards model Gastroenterology Acetylation Single-strand conformation polymorphism Genes p53 Prognosis medicine.disease Survival Rate Log-rank test Genes ras medicine.anatomical_structure Mutation Colorectal Neoplasms |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1468-3288 0017-5749 |
| DOI: | 10.1136/gut.42.5.669 |
| Popis: | Background—Somatic mutations in K-ras and TP53 may be associated with both acetylator status and prognosis in colorectal cancer.Aims—To determine whether cancers with somatic mutations are more frequent in fast acetylators and whether mutations or acetylator status influence prognosis after colorectal surgery.Patients—One hundred consecutive subjects undergoing elective surgery for colorectal cancer.Methods—Acetylator status was determined by polymerase chain reaction (PCR) genotyping for polymorphism in the N-acetyltransferase 2 (NAT2) gene. Mutations in K-ras(codon 12) and TP53 were determined by PCR analysis using restriction enzyme digestion and single strand conformation polymorphism respectively. Survival from colorectal cancer for up to five years after diagnosis was analysed using the Kaplan-Meier product limit estimator. Cox proportional hazards regression was used to compare survival rates after adjusting for tumour stage.Results—Mutations in K-ras andTP53 were independent of acetylator status. By log rank test, survival was significantly reduced in subjects with TP53mutations (p=0.003) but was not significantly related to acetylator status or the presence of K-ras mutations. After adjustment for tumour stage, subjects with both TP53 and K-ras mutations had a 4.2-fold case fatality (95% confidence interval 1.5 to 11.6) when compared with that of aTP53 negative reference group.Conclusion—The presence of both TP53and K-ras mutations in colorectal tumours is an adverse prognostic marker which is independent of tumour stage. |
| Databáze: | OpenAIRE |
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