Somatic mutations, acetylator status, and prognosis in colorectal cancer

被引:31
作者
Hardingham, JE
Butler, WJ
Roder, D
Dobrovic, A
Dymock, RB
Sage, RE
Roberts-Thomson, IC
机构
[1] Queen Elizabeth Hosp, Dept Gastroenterol, Woodville, SA 5011, Australia
[2] Queen Elizabeth Hosp, Dept Haematol Oncol, Woodville, SA 5011, Australia
[3] Queen Elizabeth Hosp, Dept Histopathol, Woodville, SA 5011, Australia
[4] S Australian Hlth Commiss, Epidemiol Unit, Adelaide, SA, Australia
关键词
colorectal cancer; TP53 and K-ras mutations; acetylator status; prognosis;
D O I
10.1136/gut.42.5.669
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 and TP53 were independent of acetylator status. By log rank test, survival was significantly reduced in subjects with TP53 mutations (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 a TP53 negative reference group. Conclusion-The presence of both TP53 and K-ras mutations in colorectal tumours is an adverse prognostic marker which is independent of tumour stage.
引用
收藏
页码:669 / 672
页数:4
相关论文
共 27 条
[1]  
ARMITAGE P, 1988, STAT METHODS MED RES, P421
[2]   FAST AND SENSITIVE SILVER STAINING OF DNA IN POLYACRYLAMIDE GELS [J].
BASSAM, BJ ;
CAETANOANOLLES, G ;
GRESSHOFF, PM .
ANALYTICAL BIOCHEMISTRY, 1991, 196 (01) :80-83
[3]   PROGNOSTIC VALUE OF P53 OVEREXPRESSION AND C-KI-RAS GENE-MUTATIONS IN COLORECTAL-CANCER [J].
BELL, SM ;
SCOTT, N ;
CROSS, D ;
SAGAR, P ;
LEWIS, FA ;
BLAIR, GE ;
TAYLOR, GR ;
DIXON, MF ;
QUIRKE, P .
GASTROENTEROLOGY, 1993, 104 (01) :57-64
[4]   PROGNOSTIC-SIGNIFICANCE OF K-RAS MUTATIONS IN COLORECTAL-CARCINOMA [J].
BENHATTAR, J ;
LOSI, L ;
CHAUBERT, P ;
GIVEL, JC ;
COSTA, J .
GASTROENTEROLOGY, 1993, 104 (04) :1044-1048
[5]   CANCER CASE-SURVIVAL RATES FOR SOUTH-AUSTRALIA - A COMPARISON WITH UNITED-STATES RATES AND A PRELIMINARY INVESTIGATION OF TIME TRENDS [J].
BONETT, A ;
RODER, D ;
ESTERMAN, A .
MEDICAL JOURNAL OF AUSTRALIA, 1988, 148 (11) :556-&
[6]   PREVALENCE OF RAS GENE-MUTATIONS IN HUMAN COLORECTAL CANCERS [J].
BOS, JL ;
FEARON, ER ;
HAMILTON, SR ;
VERLAANDEVRIES, M ;
VANBOOM, JH ;
VANDEREB, AJ ;
VOGELSTEIN, B .
NATURE, 1987, 327 (6120) :293-297
[7]  
Cohen Alfred M., 1997, P1144
[8]  
Freedman L S, 1982, Stat Med, V1, P121, DOI 10.1002/sim.4780010204
[9]  
GOH HS, 1995, CANCER RES, V55, P5217
[10]  
HARDINGHAM JE, 1993, CANCER RES, V53, P3455