Gynecological tumors revealing hereditary nonpolyposis colorectal cancer: analysis of a large Lebanese pedigree
Gynecological tumors revealing hereditary nonpolyposis colorectal cancer: analysis of a large Lebanese pedigree
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DOI：
10.1111/j.1525-1438.2006.00621.x
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发表时间：
2006-07-01
影响因子：
4.8
通讯作者：
Abou Atme, J.
中科院分区：
文献类型：
--
作者：
Akoum, R.;Ghaoui, A.;Abou Atme, J.
这项研究的目的是评估一个患有遗传性非息肉病性结直肠癌(HNPCC)的黎巴嫩大家庭中结直肠癌(CRC)和遗传性非息肉病性结直肠癌(HNPCC)相关的结肠癌的聚集性。这是一项家系分析和为期8年的前瞻性随访。采用变性高效液相色谱、短荧光片段聚合酶链式反应和DNA直接测序的方法对致病菌株突变进行检测。结直肠癌外显率高，约占发病年龄较早(21岁)的风险携带者的三分之二。结肠癌包括卵巢癌、子宫内膜癌、小肠癌、皮肤癌和脑癌，发病年龄最早可达30岁。错配修复基因突变是一个MSH2点突变，涉及内含子3的剪接供体位点(G->；A)。在对35名同意成员的基因组DNA进行仔细检查后，在其中18名成员中发现了该基因，并与该家族的癌症表型一致。早发性卵巢癌和子宫内膜癌可能是中东地区的HNPCC家族，带有MSH2胚系突变。我们建议一年两次的筛查计划，从20-25岁开始，等待有关这一主题的更多数据。
The objective of this study was to evaluate the aggregation of colorectal cancer (CRC) and hereditary nonpolyposis colorectal cancer (HNPCC)-related extracolonic cancers in an extended Lebanese family with HNPCC. This was a pedigree analysis and a prospective follow-up over an 8-year period. The causative germ line mutation was detected using denaturing high-performance liquid chromatography, polymerase chain reaction (PCR) of short fluorescent fragments, and direct DNA sequencing of purified PCR products. The penetrance of CRC is high and accounts for approximately two thirds of risk carriers with an early age of onset (21 years). The extracolonic cancer spectrum includes ovary, endometrium, small bowel, skin, and brain, with an age of onset as early as 30 years. The causative mismatch repair gene mutation is an MSH2 point mutation involving the splice donor site of intron 3 (G -> A). Scrutinized in genomic DNA from 35 consented members, it was found in 18 of them and cosegregates with the cancer phenotype in the family. Early-onset ovarian and endometrial carcinomas may reveal HNPCC families in the Middle Eastern region, with MSH2 germ line mutation. We propose a biannual screening program, starting around the age of 20-25 years, pending additional data on this topic.