Department of Surgical Oncology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Jpn J Clin Oncol. 2013 Jul;43(7):706-12. doi: 10.1093/jjco/hyt062. Epub 2013 May 8.
KRAS gene mutations are a useful predictive factor for the efficacy of anti-epidermal growth factor receptor therapeutics. Since there were no large-scale studies among Asian populations, we designed an observational nationwide study in Japan.
Formalin-fixed paraffin-embedded tissue blocks or sections from primary or metastatic lesions were obtained from patients registered between 2009 and 2010 for genomic DNA extraction. KRAS gene was analyzed by direct sequencing or Luminex assay. The primary endpoint was the frequency of KRAS gene mutations and the secondary endpoints were differences in KRAS mutation rates by various stratification factors. Univariate and multivariate analyses were performed to investigate relationships between KRAS mutation rates and patient background factors.
We analyzed 5790 eligible samples out of 5887 registered. The overall KRAS mutation rate was 37.6%, with 29.9% in codon 12 and 7.7% in codon 13, and wild type was 62.4%. A significant relationship with the KRAS mutation rate was found for gender, age, the year that the sample was prepared and the site of the primary lesion.
The KRAS mutation rate of Japanese colorectal cancer patients was 37.6%. Gender, age, the site of the primary lesion and the year that the sample was prepared were independent risk factors for KRAS mutations.
KRAS 基因突变是抗表皮生长因子受体治疗疗效的一个有用的预测因素。由于亚洲人群中没有大规模的研究，我们在日本进行了一项观察性的全国性研究。
从 2009 年至 2010 年期间登记的患者中获取原发或转移病灶的福尔马林固定石蜡包埋组织块或切片，用于提取基因组 DNA。通过直接测序或 Luminex 分析检测 KRAS 基因突变。主要终点是 KRAS 基因突变的频率，次要终点是各种分层因素的 KRAS 突变率差异。进行单因素和多因素分析以研究 KRAS 突变率与患者背景因素之间的关系。
我们分析了 5887 例登记患者中的 5790 例合格样本。总体 KRAS 突变率为 37.6%，密码子 12 中的 29.9%和密码子 13 中的 7.7%，野生型为 62.4%。KRAS 突变率与性别、年龄、样本制备年份和原发灶部位显著相关。
日本结直肠癌患者的 KRAS 突变率为 37.6%。性别、年龄、原发灶部位和样本制备年份是 KRAS 突变的独立危险因素。
