Beta3-adrenergic receptor (beta3AR) stimulates lipolysis in human fat cells, so its gene can constitute a candidate to explain a part of genetic predisposition to human obesity and related disorders. The Trp64Arg polymorphism in the beta3AR gene has been reported to be associated with insulin resistance, obesity and type 2 diabetes; little is known about its possible association with cancer. To check this association we determined the distribution of its genotypes and frequency of alleles in endometrial cancer patients with or without overweight/obesity as compared to appropriate controls. The Trp64Arg polymorphism was determined by PCR-based MspI restriction fragment length polymorphism in DNA of peripheral blood leukocytes. The study population consisted of 169 subjects, among them were 79 endometrial cancer patients and 90 controls without cancer. There were 34 obese (BMI > or = 30 kg/m2) and 22 overweight (30 BMI > or = BMI > or = 27 kg/m2) individuals among endometrial cancer patients. There was a significant (p < 0.001) difference in genotype distribution and allele frequency between endometrial cancer patients and controls without cancer. The odds ratios for the Trp/Arg and Arg/Arg genotypes as well as for the Arg allele were considerably higher than 1. Analysis of the polymorphism in the cancer group patients due to BMI revealed that the distribution of genotypes and the frequency of alleles in obese/overweight patients differed significantly from those in patients with normal weight with an odds ratio for the Trp/Arg genotype and the Arg allele of about 4. The prevalence of the Arg allele of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene may contribute to the susceptibility to endometrial cancer among obese/overweight individuals.