Single nucleotide change in the cannabinoid receptor-1 (CNR1) gene in colorectal cancer outcome

Abstract

The cannabinoid receptor-1 (CNR-1) and endogenous agonists of this receptor are present in the central and peripheral nervous systems including the gastrointestinal nervous system. The surgically rejected specimens of human colorectal cancers and paired normal tissues were studied to detect mutations in the CNR1 gene by sequencing method. The results were compared to clinicopathological parameters and correlated with overall survival time. Sixty-three colorectal cancer patients, who underwent surgical excision of colorectal carcinoma, were included in this study. The coding region of the CNR1 gene was studied: a nucleotide change (G-->A) at position 1359 was identified by direct sequencing of PCR. Thirty-eight patients had the G/G genotype (wild type) in tumor areas and 25 patients had G/A heterozygous or A/A homozygous genotype. Univariate analysis revealed 2 independent variables associated with CNR1 gene mutation. The results show that the patients with Dukes stage C and D had a 2.9 times (p = 0.04) and patients that were lymph node positive had 2.8 times (p = 0.05) greater probability of nucleotide change in CNR1 gene. Genotype G/A plus A/A had a shorter overall survival time than G/G wild-type patients (p < 0.05). Indeed nontumor paired colorectal tissues showed nucleotide change. A large number of patients with mutation in the CNR1 gene were observed. These preliminary findings highlight the importance of further studies in the use of cannabinoid analogs as receptor ligands to analyze potential therapeutic effects.