Alleles of polymorphic sites that correspond to hyperactive variants of CYP1B1 protein are significantly less frequent in Japanese as compared to American and German populations^†‡

CYP1B1 metabolites receive particular attention because of their causative role in malignant transformation of various steroid-related organs. Rare variants at residues c.701, c.1294 and c.1358 of CYP1B1 gene result in hyper-activity of protein and can lead to a higher susceptibility to estrogen-related cancers. However, in Japan, the incidences of estrogen-related cancers are remarkably lower than in Western countries. We hypothesize that polymorphisms of CYP1B1 gene can relate to lower incidence of estrogen-related diseases in the Japanese population. To test this hypothesis, the genetic distributions of six different CYP1B1 gene polymorphisms were evaluated among 200 Japanese, 200 Americans and 112 Germans by an allele-specific PCR (ASP) technique. The frequencies of rare variants at residues c.701 and c.1294 were significantly lower in the Japanese population compared to that of other populations. 5.5% of Japanese showed the genotype 701T/T (versus 9.0% in Americans and 10.7% in Germans). 6.5% of Japanese showed the genotype 1294G/G (versus 14.5% in Americans and 12.5% in Germans). The polymorphism at residue c.1358 was not detected in the Japanese population although other populations showed the variant genotypes. This report clearly demonstrates rare variants that correspond to hyper-activity of CYP1B1 protein are significantly 1ess frequent in the Japanese population. © 2003 Wiley-Liss, Inc.