Association of polymorphisms in the beta-2 and beta-3 adrenoceptor genes with risk of colorectal cancer in Japanese

Background. The adrenergic receptor system is involved in thermogenesis and in the activation of lipid mobilization in fat cells, and polymorphisms in the beta-2 and beta-3 adrenoceptor genes (BAR2 and BAR3) have been reported to be associated with obesity and insulin resistance. To examine links between polymorphisms in these genes and the risk of colorectal cancer in Japanese, we conducted the present hospital-based case-referent study. Methods. Mutations of the BAR2 gene at codon 27 (Gln27Glu) and of the BAR3 gene at codon 64 (Trp64Arg) were examined in 131 patients with colorectal cancer (cases) and in 239 cancer-free referents. We also collected information on environmental factors, using a questionnaire approach. Odds ratios (ORs) were estimated with an unconditional logistic model, after adjustment for potential confounding factors. Results. The proportional distribution of the mutations in BAR2 and BAR3 did not differ between cases and referents. Analysis of a subgroup with a higher body mass index showed that the Trp64Arg variant increased the OR (2.63; 95% confidence interval, 1.13–6.11) for colon cancer, but not for rectal cancer, compared with the Trp64 geno-type. Altered ORs for colon and rectal cancers with the Gln27Glu variant were not observed in either the subgroup with the lower body mass index or the subgroup with the higher body mass index. Conclusion. These findings suggest that the BAR3 polymorphism may alter the susceptibility to colon cancer risk in obese subjects. To confirm this finding, a further study with a larger number of subjects is now required. Received: December 11, 2000 / Accepted: March 26, 2001