Proportion and phenotype of MYH-associated colorectal neoplasia in a population-based series of Finnish colorectal cancer patients
Proportion and phenotype of MYH-associated colorectal neoplasia in a population-based series of Finnish colorectal cancer patients
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DOI：
10.1016/s0002-9440(10)63443-8
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发表时间：
2003-09-01
影响因子：
6
通讯作者：
Aaltonen, LA
中科院分区：
文献类型：
--
作者：
Enholm, S;Hienonen, T;Aaltonen, LA
碱基切除修复基因MYH的隐性遗传突变最近被发现与发生多发性腺瘤的材料中结肠直肠腺瘤和癌症的易感性相关。特别是，变异Y165C和G382D已被证明在高加索患者中发挥作用。为了评估MYH突变在人群水平上对结直肠癌负担的贡献，并在未选择的结直肠癌患者系列中检查MYH相关表型，我们确定了1042名芬兰结直肠癌患者中Y165C和G382D MYH突变的频率。4例（0.4%）患者同时存在MYH等位基因突变。虽然所有这些患者都有多发性腺瘤性息肉，但其表型往往不像以前对选定病例的研究那样极端。在癌症诊断时，结直肠腺瘤的最低数量为5个。有一个突变MYH等位基因的病例对所有外显子进行测序，以检测可能的芬兰创始人突变，但没有检测到额外的变化。在424名芬兰无癌对照中不存在Y165C和G382D变异，这表明MYH突变在人群中不富集。根据芬兰国家息肉病登记处的数据评估，myh相关的结直肠癌似乎与家族性腺瘤性息肉病相关的结直肠癌一样常见。
Recessively inherited mutations in the base excision repair gene MYH have recently been associated with predisposition to colorectal adenomas and cancer in materials selected for occurrence of multiple adenomas. In particular, variants Y165C and G382D have been shown to play a role in Caucasian patients. To evaluate the contribution of MYH mutations to colorectal cancer burden on the population level, and to examine the MYH-associated phenotype in an unselected series of colorectal cancer patients, we determined the frequencies of Y165C and G382D MYH mutations in a population-based series of 1042 Finnish colorectal cancer patients. Four (0.4%) patients had both MYH alleles mutated. Although all these patients had multiple adenomatous polyps, the phenotypes tended to be less extreme than in previous studies on selected cases. The lowest number of colorectal adenomas at the time of cancer diagnosis was five. Cases with one mutant MYH allele were subjected to sequencing of all exons to detect possible Finnish founder mutations, but no additional changes were detected. The Y165C and G382D variants were not present in 424 Finnish cancer-free controls showing that MYH mutations are not enriched in the population. As evaluated against national Finnish Polyposis Registry data MYH-associated colorectal cancer appears to be as common as colorectal cancer associated with familial adenomatous polyposis.