Department of Public Health, Sapporo Medical University School of Medicine, Hokkaido, Japan.
Eur J Cancer Prev. 2010 Mar;19(2):131-7. doi: 10.1097/CEJ.0b013e328333fbe2.
Soy isoflavones and estrogen related genes may play a major role in the etiology of prostate cancer. This study examined whether the genetic polymorphisms of estrogen receptors (ESR-alpha and ESR-beta) and cytochrome P450 19A1 (CYP19A1) modified the protective effect of isoflavones against prostate cancer. One hundred and eighty cases and 177 controls were selected from three geographic areas of Japan. The odds ratio for more than or equal to 60 versus less than 60 mg/day of the intake of isoflavones was 0.63 (95% confidence interval=0.41-0.96). The TTTA long repeat was significantly associated with an increased risk (odds ratio=1.76, 95% confidence interval=1.15-5.70). The interaction between the polymorphisms and the intake of isoflavones on prostate cancer risk was analyzed by the multifactor dimensionality reduction method. The combination of the TTTA long repeats and the minor alleles of rs10046 in CYP19A1 and rs2077647 in ESR-alpha was a high risk for prostate cancer despite greater than or equal to 60 mg isoflavones/day. The combination of the TTTA short repeat and those homozygous for the major allele of rs10046 in CYP19A1 was low risk despite less than 60 mg isoflavones/day. In conclusion, the findings of this case-control study suggest that the protective effect of isoflavones may differ between the genotypes of estrogen related genes.
大豆异黄酮和与雌激素相关的基因可能在前列腺癌的病因学中起主要作用。本研究探讨了雌激素受体（ESR-α和 ESR-β）和细胞色素 P45019A1（CYP19A1）的遗传多态性是否改变了异黄酮对前列腺癌的保护作用。从日本的三个地理区域中选择了 180 例病例和 177 例对照。每天摄入异黄酮量大于或等于 60 毫克与小于 60 毫克的比值比为 0.63（95%置信区间为 0.41-0.96）。TTTA 长重复与风险增加显著相关（比值比=1.76，95%置信区间为 1.15-5.70）。采用多因素降维法分析了多态性与异黄酮摄入对前列腺癌风险的相互作用。尽管每天摄入异黄酮量大于或等于 60 毫克，但 CYP19A1 中的 rs10046 多态性的 TTTA 长重复和 minor 等位基因以及 ESR-α 中的 rs2077647 的组合仍是前列腺癌的高危因素。尽管每天摄入异黄酮量小于 60 毫克，但 CYP19A1 中的 rs10046 多态性的 TTTA 短重复和 major 等位基因的纯合子是低危因素。总之，这项病例对照研究的结果表明，异黄酮的保护作用可能因与雌激素相关的基因的基因型而异。
