Allelic loss of chromosome 2p21-16.3 is associated with reduced survival in sporadic colorectal cancer.
BACKGROUND
Since allelic loss of genes involved in the development of colorectal cancer could serve as prognostic markers, we examined the correlation between loss of markers linked to the hMSH2/hMSH6 (2p21-16.3), hMLH1 (3p21.3), APC (5q21-22), p53 (17p13.1) and DCC (18q21.3) loci and survival in a series of 64 consecutively collected colorectal cancers.


METHODS
The association between allelic loss and survival was analysed by univariate and multivariate tests to identify independent variables of survival.


RESULTS
Loss of chromosome 2p21-16.3 reduced the overall 5-year survival from 52% to 15% (P = 0.0003). The prognostic significance was evident in patients with Dukes' A + B as well as Dukes' C tumours. A multivariate analysis comparing Dukes' staging, age at diagnosis, tumour localization, sex, loss of chromosome 2p21-16.3, 3p21.3, 5q21-22, 17p13.1 or 18q21.3 and microsatellite instability showed that only Dukes' staging (hazard ratio 3.0; 1.4-6.5 with 95% confidence interval, P = 0.0065) and loss of 2p21-16.3 (hazard ratio 6.2; 2.3-16.8 with 95% confidence interval, P = 0.0006) were independent variables of survival. Loss of 2p21-16.3 was, moreover, associated with increased loss of the other tumour suppressor loci (P = 0.012).


CONCLUSIONS
The results show that loss of 2p21-16.3 is an independent indicator of survival in patients with colorectal cancer.
Bisgaard
M L
ML
Dept. of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Jäger
A C
AC
Dalgaard
P
P
Søndergaard
J O
JO
Rehfeld
J F
JF
Nielsen
F C
FC
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D000483:Alleles; D000704:Analysis of Variance; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D005819:Genetic Markers