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Dietary Isoflavone Intake, Polymorphisms in the CYP17, CYP19, 17β-HSD1, and SHBG Genes, and Risk of Breast Cancer in Case-Control Studies in Japanese, Japanese Brazilians, and Non-Japanese Brazilians

2010; Routledge; Volume: 62; Issue: 4 Linguagem: Inglês

10.1080/01635580903441279

1532-7914

Motoki Iwasaki, Gerson Shigeaki Hamada, Inês Nobuko Nishimoto, Mário Mourão Netto, Juvenal Motola, Fábio Martins Laginha, Yoshio Kasuga, Shiro Yokoyama, Hiroshi Onuma, Hideki Nishimura, Ritsu Kusama, Minatsu Kobayashi, Junko Ishihara, Seiichiro Yamamoto, Tomoyuki Hanaoka, Shoichiro Tsugane,

Nutritional Studies and Diet

We tested the hypothesis that polymorphisms in cytochrome P450c17α (CYP17), aromatase (CYP19), 17β-hydroxysteroid dehydrogenase type I (17β-HSD1) and sex hormone-binding globulin (SHBG) genes may modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based, case-control studies in Nagano, Japan and São Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians, and 379 non-Japanese Brazilians) completed validated food frequency questionnaires. Four single nucleotide polymorphisms (SNPs) in CYP17 (rs743572), CYP19 (rs10046), 17β-HSD1 (rs605059), and SHBG (rs6259) genes were genotyped. We found no association between the 4 SNPs and breast cancer risk. In combination analyses of isoflavone intake and SNPs, an inverse association between intake and risk was limited to women with at least one A allele of the rs605059 polymorphism for all 3 populations, albeit without statistical significance. For the rs6259 polymorphism, the inverse association was limited to postmenopausal Japanese with the GG genotype (odds ratio [OR] for highest vs. lowest tertile = 0.50, 95% confidence interval [CI] = 0.29–0.87; P for trend < 0.01), and to non-Japanese Brazilians with at least one A allele (OR for consumers vs. nonconsumer = 0.21, 95% CI = 0.06–0.77). We found no remarkable difference for the rs743572 and rs10046 polymorphisms. Our findings suggest that polymorphisms in the 17β-HSD1 and SHBG genes may modify the association between isoflavone intake and breast cancer risk.