CHEK2 I157T associates with familial and sporadic colorectal cancer
CHEK2 I157T associates with familial and sporadic colorectal cancer
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DOI：
10.1136/jmg.2005.038331
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发表时间：
2006-07-01
影响因子：
4
通讯作者：
Nevanlinna, H.
中科院分区：
文献类型：
--
作者：
Kilpivaara, O.;Alhopuro, P.;Nevanlinna, H.
背景：最近，一种功能缺陷的CHEK 2变体I157 T被认为与几种癌症的风险增加有关。我们调查了CHEK 2 I157 T变异结直肠癌（CRC）的易感性在一个大的人口为基础的研究，包括一个显着数量的家族性CRC cases.Methods：我们筛选了CHEK 2 I157 T变异在一个人口为基础的系列1042芬兰CRC患者使用限制性片段长度多态性。结果：CHEK 2 I157 T基因在大肠癌患者中的频率（7.8%，76/972）显著高于健康对照组（5.3%，100/1885）（OR = 1.5，95%CI 1.1 ~ 2.1，p = 0.008）。在具有（10.4%，14/135）和不具有（7.4%，62/837）CRC家族史的患者中观察到CHEK 2 I157 T与CRC的显著关联（分别为OR = 2.1，95%CI 1.1至3.7，p = 0.01; OR= 1.4，95%CI 1.0至2.0，p = 0.03）。一个更高的变异频率的趋势，也注意到在多原发性肿瘤和家族史的任何cancer.Conclusions：CHEK 2 I157 T与CRC的风险增加：协会之间观察到家族性和散发性CRC患者。此外，I157 T在患有多种原发性肿瘤的患者以及具有任何癌症家族史的患者中的较高频率支持CHEK 2 I157 T作为多种癌症类型的易感性等位基因的作用。
Background: Recently, a functionally defective CHEK2 variant I157T has been proposed to associate with an increased risk of several types of cancer. We investigated the CHEK2 I157T variant for colorectal cancer (CRC) predisposition in a large population based study including a significant number of familial CRC cases.Methods: We screened the CHEK2 I157T variant in a population based series of 1042 Finnish CRC patients using restriction fragment length polymorphism. Mutation status was studied for correlation with clinical characteristics and family history of CRC and other cancers.Results: The frequency of CHEK2I157T was significantly higher in CRC patients (7.8%, 76/972) than in healthy population controls (5.3%, 100/1885) (OR = 1.5, 95% CI 1.1 to 2.1, p = 0.008). The significant association of CHEK2 I157T with CRC was observed among patients with ( 10.4%, 14/135) and without (7.4%, 62/837) a family history of CRC (OR = 2.1, 95% CI 1.1 to 3.7, p = 0.01; OR= 1.4, 95% CI 1.0 to 2.0, p = 0.03; respectively). A trend towards higher variant frequency was also noted among patients with multiple primary tumours and a family history of any cancer.Conclusions: CHEK2 I157T associates with an increased risk of CRC: the association was observed both among familial and sporadic CRC patients. Furthermore, the higher frequency of I157T among patients with multiple primary tumours as well as those with a family history of any cancer supports a role for CHEK2 I157T as a susceptibility allele for multiple cancer types.