Genetic polymorphisms in estrogen metabolism and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians

Abstract

Although many studies have examined associations between single nucleotide polymorphisms (SNPs) in the CYP1A1, CYP1A2 and CYP1B1 genes and breast cancer risk, no study has examined functional SNPs in the CYP3A5 gene and only a small number of studies have been investigated in Japanese populations. To examine the association between six SNPs, CYP1A1 2A, CYP1A1 2C, CYP1A2 1F, CYP1B1 Arg 48 Gly, CYP1B1 Leu 432 Val and CYP3A53 and breast cancer risk, therefore, we conducted hospital-based case-control studies in Nagano, Japan and So Paulo, Brazil including 873 pairs (403 Japanese (JJ), 81 Japanese Brazilians (JB) and 389 non-Japanese Brazilians (NJB)). Although we found no significant association in the three populations combined, subgroup analyses revealed statistically significant associations of CYP1A21F in NJB, and CYP1B1 Leu 432 Val and CYP3A53 in JJ with breast cancer risk. Compared to women with the AA genotype in CYP1A21F, the odds ratio (OR) (95% confidence interval (CI)) for NJB with the CC genotype was 0.54 (0.32-0.90); that for JJ with Leu/ValVal/Val versus Leu/Leu genotype in CYP1B1 Leu 432 Val was 0.68 (0.48-0.97); and that for JJ with 3/ 1 1/ 1 versus 3/ 3 genotype in CYP3A53 was 1.49 (1.10-2.04). Our findings provide further evidence that genetic polymorphisms related to estrogen metabolism may play a role in the development of breast cancer. © 2009 The Japan Society of Human Genetics All rights reserved.