UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia.
Dig Dis Sci. 2012 Nov;57(11):2863-72. doi: 10.1007/s10620-012-2240-2. Epub 2012 Jun 6.
Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown.
The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes.
A total of 76 patients were recruited. We used the polymerase chain reaction-denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations.
We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 %) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC).
We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC.
结直肠癌（CRC）是全球第三大常见癌症，每年约有 100 万例确诊病例。在马来西亚，CRC 是女性中第二常见的癌症，在男性中排名第一。CRC 的根本原因尚不清楚。
本研究旨在分析与 CRC 相关的基因（包括 MLH1、MSH2、KRAS 和 APC 基因）的突变。
共招募了 76 名患者。我们使用聚合酶链反应-变性高效液相色谱法检测错配修复（MMR）和 APC 基因的突变，以及 PCR 单链构象多态性筛选 KRAS 基因突变。
我们在 76 名患者中的 38 名患者中发现了 17 种错义突变。在 APC 基因中发现了 9 种突变，在 KRAS 基因中检测到 5 种突变，在 MSH2 基因中发现了 2 种突变。在 MLH1 中只发现了一种突变。在这 17 种突变中，有 8 种（47%）被预测为致病性突变。有 7 名患者被发现存在多种突变（3：MSH2 和 KRAS、1：KRAS 和 APC、1：MLH1 和 APC、2：APC 和 APC）。
我们已经建立了用于筛查 CRC 患者突变的 PCR-DHPLC 和 PCR-SSCP。本研究提供了所分析的四个基因中突变谱的快照。对患者及其家庭成员进行突变筛查将有助于早期发现 CRC，从而降低 CRC 死亡率。
