A genotype study of the c-Ha-ras-1 locus in human bladder tumors.
OBJECTIVE
To clarify the role of the c-Ha-ras-1 gene in bladder cancer predisposition and prognosis.


METHODS
The c-Ha-ras-1 locus was studied by Southern blotting in white blood cells and tumor samples obtained from 126 patients with bladder cancer (74 Ta-T1 and 52 T2-T4). A comparison with 84 unaffected patients and a survival analysis were performed.


RESULTS
The patients with bladder cancer presented 7 different c-Ha-ras-1 alleles, 12 different genotypes, heterozygosity in 49% of cases and a loss of heterozygosity (in the tumor) in 13 cases. The most frequent allele (a1, 6.6 kb) was present in 83% of patients. Heterozygosity correlated with vascular invasion in the tumor (p < 0.0001). In the small subgroup of 11 patients with rare alleles and genotypes, these alleles and genotypes occurred more often in patients with T2-T4 tumors (p < 0.01 for alleles and genotypes), aneuploid tumors (p < 0.001, p < 0.005) and tumors with vascular invasion (p < 0.01, p < 0.005). However, in this study, the majority of patients with high risk tumors possessed common alleles and genotypes. Survival analysis showed that neither the c-Ha-ras-1 genotype nor allelomorphism was an independent prognostic factor. Elsewhere, no rare allele occurred more frequently in bladder cancer affected patients than in unaffected patients.


CONCLUSIONS
This study confirms c-Ha-ras-1 gene polymorphism in a bladder cancer affected population and, in some cases, a loss of genetic material in the vicinity of this locus. No specific genotype can be implicated in the predisposition to bladder carcinoma, and c-Ha-ras-1 genotyping appears of limited value in the clinical management of these patients.
Bittard
H
H
Servide d'Urologie, CHU Besançon, France.
Descotes
F
F
Billerey
C
C
Lamy
B
B
Adessi
G R
GR
D002874:Chromosome Mapping; D011905:Genes, ras / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality