Association of the C677T polymorphism in the MTHFR gene with breast and/or ovarian cancer risk in Jewish women
Association of the C677T polymorphism in the MTHFR gene with breast and/or ovarian cancer risk in Jewish women
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DOI：
10.1016/s0959-8049(00)00306-3
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发表时间：
2000-12-01
影响因子：
8.4
通讯作者：
Friedman, E
中科院分区：
文献类型：
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作者：
Gershoni-Baruch, R;Dagan, E;Friedman, E
亚甲基四氢叶酸还原酶（MTHFR）基因中的C677 T突变与纯合子中酶活性降低、高同型半胱氨酸血症和动脉粥样硬化风险增加相关。我们检测了491名患有散发性（n = 355; 72%）或遗传性（n = 136; 28%）乳腺癌和/或卵巢癌的犹太妇女和69名无症状BRCA 1/2突变携带者中该突变的频率及其与疾病模式的相关性，对三种主要的犹太人创始人BRCA 1/2突变（185 delAG，5382 insC和6174 delT）进行了基因分型。677 T纯合子在散发性乳腺癌和/或卵巢癌患者（71/355; 20.0%）和BRA 1/2突变携带者（43/205; 21.0%）中分布均匀（P =无显著性）。677 T纯合子在42岁之前（22/122; 18.0%）和42岁之后（42/243; 17.3%）诊断为乳腺癌的女性中均匀分布。在BRCA 1/2携带者中，677 T纯合子在有癌症表现者（32/136; 23.5%）和无症状个体（11/69; 15.9%）中的比例无显著差异。双侧乳腺癌、乳腺癌和卵巢癌患者的677 T纯合子率（24/72; 33.3%）高于单侧乳腺癌患者（64/365; 17.5%）（P = 0.0026）。发病率的差异（一个与多个乳腺/卵巢肿瘤）主要归因于677 T纯合性，部分归因于BRCA 1/2突变。这些数据的证实，即677 T等位基因在双侧乳腺癌或乳腺癌和卵巢癌联合病例中明显更常见，将具有重要的临床意义。(C)2000爱思唯尔科技有限公司版权所有。
The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with reduced enzyme activity, hyperhomocysteinaemia and increased risk for atherosclerosis in homozygotes. We examined the frequency of this mutation and its association with disease pattern in 491 Jewish women with either sporadic (n = 355; 72%) or hereditary (n = 136; 28%) breast and/or ovarian cancer and in 69 asymptomatic BRCA1/2 mutation carriers, genotyped for the three predominant Jewish founder BRCA1/2 mutations (185delAG, 5382insC and 6174delT). 677T homozygotes were equally distributed among women with sporadic breast and/or ovarian cancer (71/355; 20.0%) and among BRA1/2 mutation carriers (43/205; 21.0%) (P = non-significant). 677T homozygotes were equally distributed among women diagnosed with breast cancer prior to (22/122; 18.0%) and after 42 years of age (42/243; 17.3%). Among BRCA1/2 carriers, the rate of 677T homozygotes in manifesting cancer (32/136; 23.5%) and asymptomatic individuals (11/69; 15.9%) was not significantly different. The rate of 677T homozygotes (24/72; 33.3%) was higher (P = 0.0026) among women with bilateral breast cancer and those with both breast and ovarian carcinoma than among those with unilateral breast cancer (64/365; 17.5%). Differences in morbidity (one versus multiple breast/ovarian tumours) are mainly attributed to 677T homozygosity and partly to BRCA1/2 mutations. Confirmation of these data, namely, that the 677T allele is significantly more common in cases of bilateral breast cancer or combined breast and ovarian cancer would have important clinical implications. (C) 2000 Elsevier Science Ltd. All rights reserved.