Case-control studies on the association between breast cancer risk and genetic polymorphisms of estrogen metabolizing enzymes

乳腺癌风险与雌激素代谢酶基因多态性关联的病例对照研究

• 批准号: 12670383
• 负责人: HAMAJIMA Nobuyuki
• 金额: $ 2.18万
• 依托单位: Aichi Cancer Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670383/
• 关键词: Female breast cancer; Hormone metabolizing enzymes; Genetic polymorphisms; Disease risk; Case-control study; PCR-CTPP; INterleukin 1B; Beta-adrenoceptor 2; CYP19; CYP17; catechol-O-methyltranferase

Case-control studies on the association between breast cancer risk and genetic polymorphisms mainly relating to estrogens were conducted for patients (239 breast cancer patients and 186 non-cancer controls) of Aichi Cancer Center Hospital of Aichi Cancer Center Hospital. After written informed consent for genotyping was obtained, the participants were asked to provide lifestyle information and a peripheral blood sample. Genotyping was conducted mainly with PCR-RFLP. In 2000-2001, the association of breast cancer risk with estrogen-related polymorphisms ; cytochrome p450 17 (CYP17) C-34T, cytochrome p450 19 (CYP19) Trp39Arg, catechol-O-methyltransferase (COMT) Val158Met, and interleukin (IL) 1B C-31T, obesity-related polymorphisms! beta-adrenoceptor 2 (BAR2) Gln27Glu and beta-adrenoceptor 3 (BAR3) Trp64Arg, carcinogen-metabolism-related polymorphism ; NAD(P)H:qmnone oxidoreductase 1 (NQO1) C609T, and carcinogenesis-related polymorphisms; p53 Arg72Pro and transforming growth factor (TGf) B1 T29C were examined. No associations were observed for CYP17 C-34T, CYP19 Trp39Arg, COMT Val158Met, BAR3 Trp64Arg, and NQO1 C609T. Concerning BAR2 Gln27Glu, a significant risk reduction was observed among women harboring 27Glu who gave the first birth at age 25 years or younger. The odds ratio for IL-B -31TT genotype relative to -31CC genotype was significantly reduced (OR=0.54, 95 % confidence interval, 0.33-0.90), especially among postmenopausal women (OR=0.29, 0. 14-0.61).

以爱知癌中心医院的患者（239名乳腺癌患者和186名非癌症对照）为对象，对乳腺癌风险与主要与雌激素相关的遗传多态性之间的关联进行了病例对照研究。在获得基因分型的书面知情同意书后，要求参与者提供生活方式信息和外周血样本。基因分型主要采用PCR-RFLP。在2000-2001年，乳腺癌风险与雌激素相关的多态性;细胞色素p450 17（CYP 17）C-34 T，细胞色素p450 19（CYP 19）Trp 39 Arg，儿茶酚-O-甲基转移酶（COMT）Val 158 Met和白细胞介素（IL）1B C-31 T，肥胖相关的多态性！β-肾上腺素受体2（BAR 2）Gln 27 Glu和β-肾上腺素受体3（BAR 3）Trp 64 Arg，致癌物代谢相关多态性; NAD（P）H：qmnone氧化还原酶1（NQO 1）C609 T，以及致癌相关多态性;检查了p53 Arg 72 Pro和转化生长因子（TGf）B1 T29 C。未观察到CYP 17 C-34 T、CYP 19 Trp 39 Arg、COMT Val 158 Met、BAR 3 Trp 64 Arg和NQO 1 C609 T的相关性。关于BAR 2 Gln 27 Glu，在25岁或以下首次生育的携带27 Glu的妇女中观察到显著的风险降低。IL-B-31 TT基因型相对于-31 CC基因型的优势比显著降低（OR=0.54，95%可信区间，0.33-0.90），尤其是在绝经后妇女中（OR=0.29，0.95）。14-0.61）。

项目成果

Hamajima N: "Limited association between a catechol-O-methyltransferase (COMT) polymorphism and breast cancer risk in Japan"International Journal Clinical Oncology. (印刷中).

Hamajima N：“儿茶酚-O-甲基转移酶 (COMT) 多态性与日本乳腺癌风险之间的有限关联”《国际临床肿瘤学杂志》（出版中）。

浜島信之: "乳がんリスクと遺伝子多型"乳がんの臨床. 15・2. 123-135 (2000)

Nobuyuki Hamashima：“乳腺癌风险和遗传多态性”临床乳腺癌15・2（2000）。

Hamajima N, et al: "NAD(P)H : quinone oxidoreductase 1 (NQO1) C609T polymorphism and risk of eight cancers for Japanese"Int J Clin Oncol. (in press).

Hamajima N 等人：“NAD(P)H：醌氧化还原酶 1 (NQO1) C609T 多态性和日本人患八种癌症的风险”Int J Clin Oncol。

Hamajima N, et al: "No association of the 5' promotor region polymorphism of CYP17 with breast cancer risk in Japan"Jpn J Cancer Res. 91(9). 880-885 (2000)

Hamajima N 等人：“CYP17 的 5 启动子区域多态性与日本乳腺癌风险没有关联”Jpn J Cancer Res。

Huang X-E: "Possible association of β2-and β3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer"Breast Cancer Research. 3・4. 264-269 (2001)

黄X-E：“β2-和β3-肾上腺素能受体基因多态性与乳腺癌易感性的可能关联”《乳腺癌研究》3・4（2001）。