Winder Thomas, Mündlein Axel, Rhomberg Simone, Dirschmid Klaus, Hartmann Bernd L, Knauer Michael, Drexel Heinz, Wenzl Etienne, De Vries Alexander, Lang Alois
Department of Medicine, Academic Teaching Hospital Feldkirch, A-6807 Feldkirch, Austria.
Oncol Rep. 2009 May;21(5):1283-7. doi: 10.3892/or_00000352.
A glycine to valine substitution at codon 12 (G12V) in Kirsten-Ras (K-Ras) gene has been associated with reduced overall survival in colorectal cancer patients; however, the effect of other K-Ras mutations than G12V still remains unclear. Therefore, we investigated the role of different K-Ras mutations on overall survival in a homogeneous, large patient cohort with standardized therapy and uniform analysis of K-Ras mutation status. The study included 342 patients with histopathologically proven colorectal cancer. Survival data were provided by the federal agency for statistics in Austria. Occurrence of K-Ras mutations at codons 12, 13 and 61 were determined by capillary sequencing. The overall K-Ras mutation frequency in carcinoma tissue was 28%. Carriers of the G12V mutation at the K-Ras gene showed a significantly decreased overall survival compared to carriers of the wild-type [HR=2.56 (1.15-5.69)]. Other mutations than G12V were associated with better overall survival compared to wild-type [HR=0.44 (0.2-0.99)]. In conclusion, for the first time, our study showed clearly that different types of K-Ras mutations are conversely associated with overall survival in patients with colorectal cancer.
Kirsten - Ras（K - Ras）基因第12密码子处的甘氨酸到缬氨酸替换（G12V）与结直肠癌患者的总生存期缩短有关；然而，除G12V之外的其他K - Ras突变的影响仍不清楚。因此，我们在一个接受标准化治疗且K - Ras突变状态分析统一的同质大型患者队列中，研究了不同K - Ras突变对总生存期的作用。该研究纳入了342例经组织病理学证实的结直肠癌患者。生存数据由奥地利联邦统计机构提供。通过毛细管测序确定第12、13和61密码子处K - Ras突变的发生情况。癌组织中K - Ras的总体突变频率为28%。与野生型携带者相比，K - Ras基因G12V突变携带者的总生存期显著缩短[风险比（HR）=2.56（1.15 - 5.69）]。与野生型相比，除G12V之外的其他突变与更好的总生存期相关[HR = 0.44（0.2 - 0.99）]。总之，我们的研究首次明确表明，不同类型的K - Ras突变与结直肠癌患者的总生存期呈相反相关。
