甲基代谢基因多态性作为意大利BRCA1/2携带者乳腺癌风险的修饰因素
Methyl group metabolism gene polymorphisms as modifier of breast cancer risk in Italian BRCA1/2 carriers.
作者信息
Pepe C, Guidugli L, Sensi E, Aretini P, D'Andrea E, Montagna M, Manoukian S, Ottini L, Radice P, Viel A, Bevilacqua G, Caligo M A
机构信息
Section of Oncogenetics, Division of Pathology, Department of Oncology, University of Pisa, Via Roma, 57, PI,, I-56126 Pisa, Italy.
出版信息
Breast Cancer Res Treat. 2007 May;103(1):29-36. doi: 10.1007/s10549-006-9349-y. Epub 2006 Dec 7.
BRCA1 and 2 are major cancer susceptibility genes but their penetrance is highly variable. The folate metabolism plays an important role in DNA methylation and its alterated metabolism is associated with cancer risk. The role of allele variants 677T and 1298C (MTHFR gene) and 2756G (MS gene) has been investigated as potentially modifying factors of BRCA gene penetrance, evaluated as age at first diagnosis of cancer, in 484 BRCA1/BRCA2 carriers and in 108 sporadic breast cancer cases as a control group. The genotype analysis has been performed by means of PCR/RFLP's. The analysis of association between a particular genotype and disease risk was performed using Cox Regression with time to breast or ovarian cancer onset as the end-point. The presence of 677T allele confers an increased risk of breast cancer in BRCA1 carriers (P = 0.007) and the presence of 1298C allele confers an increased risk of breast cancer in sporadic cases (P = 0.015).
BRCA1和BRCA2是主要的癌症易感基因，但其外显率高度可变。叶酸代谢在DNA甲基化中起重要作用，其代谢改变与癌症风险相关。等位基因变体677T和1298C（MTHFR基因）以及2756G（MS基因）的作用已被研究，作为BRCA基因外显率的潜在修饰因素，以首次诊断癌症的年龄来评估，研究对象为484名BRCA1/BRCA2携带者以及作为对照组的108例散发性乳腺癌病例。基因型分析通过PCR/RFLP方法进行。使用Cox回归分析特定基因型与疾病风险之间的关联，以乳腺癌或卵巢癌发病时间作为终点。677T等位基因的存在使BRCA1携带者患乳腺癌的风险增加（P = 0.007），1298C等位基因的存在使散发性病例患乳腺癌的风险增加（P = 0.015）。
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