Inoue Hiroshi, Shibuta Kenji, Matsuyama Ayumi, Yoshinaga Keishi, Sadanaga Noriaki, Ueo Hiroaki, Barnard Graham F, Mori Masaki
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu 874-0838, Japan.
Oncol Rep. 2005 Sep;14(3):707-12.
Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens. It has been reported that COMT polymorphism is a representative genetic trait related to the susceptibility of an individual to breast cancer. However, there is no consensus concerning the association between breast cancer in Japanese patients and COMT polymorphism. To analyze the polymorphism distribution in Japanese patients with breast cancer, a molecular genotyping method using a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used. Based on an analysis of 201 Japanese patients with breast cancer and 352 healthy control subjects, a significant difference was observed in either the distribution of genotypes (p=0.03) or allele frequencies between the two groups (p=0.01). The relative risk of breast cancer for genotypes (COMT(Met/Met) and COMT(Val/Met)) including the variant allele (COMT(Met)) was 1.47 compared to the wild allele (COMT(Val)) and homozygote (COMT(Val/Val)). Furthermore, the distribution of genotypes in post-menopausal patients with breast cancer showed a significant difference with that of healthy subjects of the same menopausal status (p=0.01). No significant difference was found between the distribution of genotypes and clinicopathological features of the cancer. These results suggest that COMT polymorphism may thus be implicated as a genetic trait affecting the susceptibility of an individual to breast cancer in a Japanese population and be an important genetic risk factor in the development of breast cancer in post-menopausal women.
多态性儿茶酚-O-甲基转移酶（COMT）催化儿茶酚雌激素的O-甲基化。据报道，COMT多态性是与个体患乳腺癌易感性相关的代表性遗传特征。然而，关于日本患者乳腺癌与COMT多态性之间的关联尚无共识。为分析日本乳腺癌患者的多态性分布，采用了基于聚合酶链反应的限制性片段长度多态性（PCR-RFLP）分子基因分型方法。基于对201例日本乳腺癌患者和352例健康对照者的分析，两组之间在基因型分布（p = 0.03）或等位基因频率（p = 0.01）上均观察到显著差异。与野生等位基因（COMT(Val)）和纯合子（COMT(Val/Val)）相比，包括变异等位基因（COMT(Met)）的基因型（COMT(Met/Met)和COMT(Val/Met)）患乳腺癌的相对风险为1.47。此外，绝经后乳腺癌患者的基因型分布与相同绝经状态的健康受试者相比存在显著差异（p = 0.01）。在癌症的基因型分布与临床病理特征之间未发现显著差异。这些结果表明，COMT多态性可能是影响日本人群个体患乳腺癌易感性的遗传特征，并且是绝经后女性乳腺癌发生的重要遗传危险因素。
