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

Abstract

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.

ACKNOWLEDGMENTS

This study was supported by a Grant-in-Aid for Research on Risk of Chemical Substances from the Ministry of Health, Labour and Welfare of Japan and Grants-in-Aid for Scientific Research on Priority Areas (17015049) and for Young Scientists (B) (17790378 and 19790415) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Japan Society for the Promotion of Science. We are grateful to the members of the “São Paulo-Japan Breast Cancer Study Group”: S. Ikeda and C. Nishimoto (Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo); C. I. Yamaguchi, C. M. Kunieda, and S. S. Sugama (Nikkei Disease Prevention Center, São Paulo); C. K. Taniguchi and J. A. Marques (Departamento de Ginecologia, Hospital Pérola Byington, São Paulo); M. R. Eichhorn (Departamento de Nutrição, Hospital Pérola Byington, São Paulo); H. Iyeyasu, M. S. Maciel, S. M. T. Carvalho, J. B. D. Collins, and C. E. M. Fontes (Departamento de Mastologia, Hospital A.C. Camargo, São Paulo); L. P. Kowalski and J. M. F. Toyota (Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia, A. C. Camargo Hospital, São Paulo); E. M. Barbosa (Departamento de Mastologia, Instituto Brasileiro de Controle ao Câncer, São Paulo); O. Ferraro (Departamento de Mastologia, Hospital do Servidor Público Estadual Francisco Morato de Oliveira, São Paulo); R. Anzai (Departamento de Mastologia, Hospital Santa Cruz); E. H. Hotta and D. A. Petti (Instituto de Ginecologia e Mastologia, Hospital Beneficencia Portuguesa); and S. Mendes (Instituto Brasileiro de Mastologia e Ginecologia, Hospital Beneficencia Portuguesa).

Notes

^aAbbreviations are as follows: CYP, cytochrome P450, 17β-HSD1, 17β-hydroxysteroid dehydrogenase type I; SHBG, sex hormone-binding globulin.

^bConditional model adjusting for menopausal status (premenopausal, postmenopausal), number of births (0, 1, 2, 3, 4, 5+), family history of breast cancer (yes, no), smoking status (never, past, current smokers), moderate physical activity in the past 5 yr (no, less than 3 days/mo, 1–4 days/wk, more than 5 days/wk), and vitamin supplement use (yes, no).

^aAbbreviations are as follows: CYP, cytochrome P450, 17β-HSD1, 17β-hydroxysteroid dehydrogenase type I; SHBG, sex hormone-binding globulin.

^bNo. of cases/No. of controls.

^cConditional model adjusting for menopausal status (premenopausal, postmenopausal), number of births (0, 1, 2, 3, 4, 5+), family history of breast cancer (yes, no), smoking status (never, past, current smokers), moderate physical activity in the past 5 yr (no, less than 3 days/mo, 1–4 days/wk, more than 5 days/wk), and vitamin supplement use (yes, no). For stratified analyses according to menopausal status, an unconditional model adjusting for age, area, number of births (0, 1, 2, 3, 4, 5+), family history of breast cancer (yes, no), smoking status (never, past, current smokers), moderate physical activity in the past 5 yr (no, less than 3 days/mo, 1–4 days/wk, more than 5 days/wk), and vitamin supplement use (yes, no).

^dORs and 95% CIs with statistical significance are written in bold.