A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2
A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2
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DOI：
10.1073/pnas.2132286100
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发表时间：
2003-10-28
影响因子：
11.1
通讯作者：
Markowitz, SD
中科院分区：
文献类型：
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作者：
Wiesner, GL;Daley, D;Markowitz, SD
结直肠癌是美国成年人癌症死亡的第二大原因。家族性腺瘤性息肉病和遗传性非息肉病性结直肠癌这两种常染色体显性遗传形式的疾病可能占所有病例的5%。然而，在大约20%的额外结肠癌病例中，受影响的个体报告了一级亲属的结肠癌家族史。类似的家族性结肠癌和早发性结肠腺瘤也有报道。为了确定这种家族聚集性是偶然出现的还是反映了遗传性结肠癌易感性，我们进行了全基因组扫描，以检测53个家族中的遗传连锁，其中两个或多个兄弟姐妹在65岁或更年轻时患有结肠癌或患有尺寸>1 cm或显示高度异型增生的晚期结肠腺瘤。在该队列中，我们发现疾病与染色体区域9q22.2-31.2的遗传连锁[P = 0.00045]，其模式与常染色体显性疾病等位基因一致。这些数据表明，一个单一的基因座可以有助于疾病的易感性，在一个子集的患者与非综合征形式的家族性结直肠肿瘤。
Colorectal cancer is the second most leading cause of cancer death among adult Americans. Two autosomal dominant hereditary forms of the disease, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, together account for perhaps 5% of all cases. However, in approximate to20% of additional colon cancer cases, the affected individuals report a family history of colon cancer in a first-degree relative. Similar familial clusters of colon cancer and early-onset colon adenomas have also been reported. To determine whether such familial aggregations arise by chance or reflect a hereditary colon cancer susceptibility, we conducted a whole genome scan to test for genetic linkage in 53 kindreds in which two or more siblings were affected by age 65 or younger with colon cancer or with advanced colon adenomas that were >1 cm in size or that showed high-grade dysplasia. In this cohort we found genetic linkage of disease [P = 0.00045) to chromosomal region 9q22.2-31.2 in a pattern consistent with autosomal dominant disease alleles. These data suggest that a single locus can contribute to disease susceptibility in a subset of patients with nonsyndromic forms of familial colorectal neoplasia.