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基于芬兰结直肠癌患者群体的MYH相关结直肠肿瘤的比例和表型

Proportion and phenotype of MYH-associated colorectal neoplasia in a population-based series of Finnish colorectal cancer patients.

作者信息

Enholm Susa, Hienonen Tuija, Suomalainen Anu, Lipton Lara, Tomlinson Ian, Kärjä Vesa, Eskelinen Matti, Mecklin Jukka-Pekka, Karhu Auli, Järvinen Heikki J, Aaltonen Lauri A

机构信息

Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 3, Helsinki, FIN-00014, Finland.

出版信息

Am J Pathol. 2003 Sep;163(3):827-32. doi: 10.1016/S0002-9440(10)63443-8.

Abstract

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.

摘要

碱基切除修复基因MYH的隐性遗传突变最近与在因多发腺瘤而入选的人群中患结直肠腺瘤和癌症的易感性相关。特别是,已证明Y165C和G382D变异在白种人患者中起作用。为了在人群水平上评估MYH突变对结直肠癌负担的影响,并在未经选择的一系列结直肠癌患者中检查与MYH相关的表型,我们在一项基于人群的1042例芬兰结直肠癌患者系列中确定了Y165C和G382D MYH突变的频率。4例(0.4%)患者的两个MYH等位基因均发生突变。尽管所有这些患者都有多个腺瘤性息肉,但表型往往不如先前对选定病例的研究中那么严重。癌症诊断时结直肠腺瘤的最少数量为5个。对具有一个突变MYH等位基因的病例进行了所有外显子的测序,以检测可能的芬兰始祖突变,但未检测到其他变化。424名芬兰无癌对照中不存在Y165C和G382D变异,这表明MYH突变在人群中并未富集。根据芬兰国家息肉病登记数据评估,与MYH相关的结直肠癌似乎与与家族性腺瘤性息肉病相关的结直肠癌一样常见。

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