Gastroenterology Department, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Catalonia, Barcelona, Spain.
Fam Cancer. 2009;8(4):525-31. doi: 10.1007/s10689-009-9282-4. Epub 2009 Aug 15.
Colorectal cancer (CRC) risk associated with germline monoallelic MUTYH mutations remains controversial, although a slightly increased risk for this disease has been suggested. MUTYH and MSH6 proteins act in cooperation during the DNA repair process. Based on this interaction, it was hypothesized that the combination of heterozygote germline mutations in both genes could result in an increased CRC risk. To further clarify the interaction between MUTYH and MSH6, we analyzed the prevalence of MSH6 mutations in a cohort of CRC patients and controls previously tested for MUTYH mutations: CRC patients with and without a monoallelic MUTYH mutation (group I, n = 26; group II, n = 50, respectively), and healthy carriers with a monoallelic MUTYH mutation (group III, n = 21). In group I, we found three patients (11.5%) with MSH6 mutations, a missense mutation (p.R635G), a change in the 3'UTR region (c.*4098A > C) and a nonsense mutation (p.Q982X). In group II and III, no mutations were detected. In CRC patients, MSH6 mutations were more frequently found in MUTYH mutation carriers than in noncarriers (11.5% vs. 0%, P = 0.037). CRC patients carrying monoallelic MUTYH mutations harbor more frequently concomitant MSH6 mutations than patients without them, thus suggesting that both genes could act cooperatively and confer together an increased CRC risk.
结直肠癌（CRC）与种系单等位基因突变 MUTYH 相关的风险仍然存在争议，尽管已经提出这种疾病的风险略有增加。MUTYH 和 MSH6 蛋白在 DNA 修复过程中协同作用。基于这种相互作用，假设这两个基因的杂合种系突变的组合可能导致 CRC 风险增加。为了进一步阐明 MUTYH 和 MSH6 之间的相互作用，我们分析了先前测试 MUTYH 突变的 CRC 患者和对照队列中 MSH6 突变的患病率：具有单等位基因突变 MUTYH 的 CRC 患者和无单等位基因突变 MUTYH 的患者（分别为组 I，n = 26；组 II，n = 50），以及具有单等位基因突变 MUTYH 的健康携带者（组 III，n = 21）。在组 I 中，我们发现三名患者（11.5%）存在 MSH6 突变，包括错义突变（p.R635G）、3'UTR 区域改变（c.*4098A > C）和无义突变（p.Q982X）。在组 II 和组 III 中，未检测到突变。在 CRC 患者中，MUTYH 突变携带者中 MSH6 突变的频率高于非携带者（11.5% vs. 0%，P = 0.037）。携带单等位基因突变 MUTYH 的 CRC 患者比不携带的患者更频繁地携带 MSH6 突变，这表明这两个基因可以协同作用并共同增加 CRC 的风险。
