Inherited colorectal polyposis and cancer risk of the APC I1307K polymorphism
Inherited colorectal polyposis and cancer risk of the APC I1307K polymorphism
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DOI：
10.1086/302262
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发表时间：
1999-02-01
影响因子：
9.8
通讯作者：
Redston, M
中科院分区：
文献类型：
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作者：
Gryfe, R;Di Nicola, N;Redston, M
APC基因的生殖系和体细胞截短突变被认为分别在家族性腺瘤性息肉病综合征和散发性结直肠癌发生中启动结直肠肿瘤形成。最近，在6%-7%的德系犹太人中鉴定出APC基因密码子1307（I1307 K）的异亮氨酸->赖氨酸多态性。为了评估这种常见的APC等位基因变异在结直肠癌发生中的风险，我们分析了一个大型队列的患有腺瘤性息肉和/或结直肠癌的德系犹太人的APC I1307 K多态性。476例患者中有48例（10.1%）发现APC I1307 K等位基因。与两个独立的人群对照组的频率相比，APC I1307 K等位基因与结直肠肿瘤的估计相对风险为1.5-1.7相关（均P = 0.01）。此外，与非携带者相比，APC I1307 K携带者每例患者的腺瘤和结直肠癌数量增加（P = 0.03），诊断时年龄更小。我们的结论是APC I1307 K变异导致腺瘤形成增加，并直接导致所有德系犹太人结直肠癌的3%-4%。携带者的估计相对风险可能证明对360，000名预期携带该等位基因的美国人进行特定的临床筛查是合理的，并且在长期结局研究中进行基因检测可能会对该人群的结直肠癌预防产生显着影响。
Germ-line and somatic truncating mutations of the APC gene are thought to initiate colorectal tumor formation in familial adenomatous polyposis syndrome and sporadic colorectal carcinogenesis, respectively, Recently, an isoleucine-->lysine polymorphism at codon 1307 (I1307K) of the APC gene has been identified in 6%-7% of the Ashkenazi Jewish population. To assess the risk of this common APC allelic variant in colorectal carcinogenesis, we have analyzed a large cohort of unselected Ashkenazi Jewish subjects with adenomatous polyps and or colorectal cancer, for the APC I1307K polymorphism. The APC I1307K allele was identified in 48 (10.1%) of 476 patients. Compared with the frequency in two separate population control groups, the APC I1307K allele is associated with an estimated relative risk of 1.5-1.7 for colorectal neoplasia (both P = .01). Furthermore, compared with noncarriers, APC I1307K carriers had increased numbers of adenomas and colorectal cancers per patient (P = .03), as well as a younger age at diagnosis. We conclude that the APC I1307K variant leads to increased adenoma formation and directly contributes to 3%-4% of all Ashkenazi Jewish colorectal cancer. The estimated relative risk for carriers may justify specific clinical screening for the 360,000 Americans expected to harbor this allele, and genetic testing in the setting of long-term-outcome studies may impact significantly on colorectal cancer prevention in this population.