Background: The H-ras locus has been suggested to play an important ro
le in susceptibility to cancer. However, the results remain controvers
ial. Methods: In order to elucidate the potential role of the H-ras lo
cus in colorectal carcinogenesis, 142 colorectal tumors with matched n
ormal samples were studied for genomic instability and loss of heteroz
ygosity (LOH) and 143 healthy samples of white blood cell DNA were exa
mined by PCR, for H-ras allelic polymorphism. Results: Nine percent of
colorectal cancer patients constitutionally presented at least one ra
re allele versus 1.4% of healthy individuals (P = 0.0034). The risk of
developing colorectal cancer increased significantly with the presenc
e of rare H-ras alleles (odds ratio = 7.10 and 95% confidence interval
= 1.92-26.35). The genotype associating one common allele and one rar
e allele was overrepresented in cancer patients (P < 0.01). No associa
tions were observed between the rare alleles and tumor site or with th
e aggressiveness of cancer. Low frequencies of LOH (5%) and genetic in
stability (0.7%) at the H-ras locus were found in our colorectal cance
r set. Conclusions: Consequently, the presence of uncommon alleles at
the H-ras locus appeared to be an informative genetic marker.