Dietary isoflavone intake, polymorphisms in the CYP17, CYP19, 17beta-HSD1, and SHBG genes, and risk of breast cancer in case-control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians.
We tested the hypothesis that polymorphisms in cytochrome P450c17alpha (CYP17), aromatase (CYP19), 17beta-hydroxysteroid dehydrogenase type I (17beta-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 Sao 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), 17beta-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 17beta-HSD1 and SHBG genes may modify the association between isoflavone intake and breast cancer risk.
Iwasaki
Motoki
M
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan. moiwasak@ncc.go.jp
Hamada
Gerson Shigeaki
GS
Nishimoto
Ines Nobuko
IN
Netto
Mario Mourão
MM
Motola
Juvenal
J
Laginha
Fábio Martins
FM
Kasuga
Yoshio
Y
Yokoyama
Shiro
S
Onuma
Hiroshi
H
Nishimura
Hideki
H
Kusama
Ritsu
R
Kobayashi
Minatsu
M
Ishihara
Junko
J
Yamamoto
Seiichiro
S
Hanaoka
Tomoyuki
T
Tsugane
Shoichiro
S
D000154:Aconitate Hydratase / Q000235:genetics; D000328:Adult; D000368:Aged; D001141:Aromatase / Q000235:genetics; D001938:Brazil / Q000453:epidemiology; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000517:prevention & control*; D016022:Case-Control Studies; D004032:Diet; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage*; D007564:Japan / Q000453:epidemiology / Q000208:ethnology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012738:Sex Hormone-Binding Globulin / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics*; D011795:Surveys and Questionnaires; D055815:Young Adult
D012739:Gonadal Steroid Hormones; D007529:Isoflavones; D012738:Sex Hormone-Binding Globulin; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; D013250:Steroid Hydroxylases; D001141:Aromatase; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D000154:Aconitate Hydratase