Affiliations of authors: Division of Hematology/Division of Medical Oncology (WIG), Division of Biomedical Statistics & Informatics (MRM, GDN), Cancer Center Statistics (DJS), Division of Medical Oncology (SRA, AG, JMH, RRM), Division of Gastroenterology & Hepatology/Division of Medical Oncology (FAS), Division of Gastroenterology & Hepatology (PJL), Molecular Genetics (SNT), Mayo Clinic, Rochester, MN; Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH (RMG); Division of Hematology/Oncology, Vanderbilt University, Nashville, TN (EC); Section of Hematology/Medical Oncology, Lehigh Valley Health Network, Allentown, PA (SN); Cancer Prevention & Control Program, University of Hawaii Cancer Center, Honolulu, HI (JLB).
J Natl Cancer Inst. 2014 Jun 12;106(7). doi: 10.1093/jnci/dju106. Print 2014 Jul.
KRAS and BRAF (V600E) mutations are important predictive and prognostic markers, respectively, in colon cancer, but little is known about patient and clinical factors associated with them.
Two thousand three hundred twenty-six of 3397 patients in the N0147 phase III adjuvant trial for stage III colon cancer completed a patient questionnaire. Primary tumors were assessed for KRAS and BRAF (V600E) mutations and defective mismatch repair (dMMR) status. Logistic regression models and categorical data analysis were used to identify associations of patient and tumor characteristics with mutation status. All statistical tests were two-sided.
KRAS (35%) and BRAF (V600E) (14%) mutations were nearly mutually exclusive. KRAS mutations were more likely to be present in patients without a family history of colon cancer and never smokers. Tumors with KRAS mutations were less likely to have dMMR (odds ratio [OR] = 0.21; 95% confidence interval [CI] = 0.15 to 0.31; P < .001) and high-grade histology (OR = 0.73; 95% CI = 0.59 to 0.92; P < .001) but were more often right-sided. Among KRAS-mutated tumors, those with a Gly13Asp mutation tended to have dMMR and high-grade histology. Tumors with BRAF (V600E) mutations were more likely to be seen in patients who were aged 70 years or older (OR = 3.33; 95% CI = 2.50 to 4.42; P < .001) and current or former smokers (OR = 1.64; 95% CI = 1.26 to 2.14; P < .001) but less likely in non-whites and men. Tumors with BRAF (V600E) mutations were more likely to be right-sided and to have four or more positive lymph nodes, high-grade histology, and dMMR.
Specific patient and tumor characteristics are associated with KRAS and BRAF (V600E) mutations.
KRAS 和 BRAF（V600E）突变分别是结直肠癌的重要预测性和预后标志物，但人们对与之相关的患者和临床因素知之甚少。
在 III 期 N0147 辅助试验中，对 3397 例 III 期结肠癌患者中的 2326 例完成了患者问卷调查。对原发性肿瘤进行 KRAS 和 BRAF（V600E）（14%）突变和错配修复缺陷（dMMR）状态评估。使用逻辑回归模型和分类数据分析来确定患者和肿瘤特征与突变状态的关联。所有统计检验均为双侧检验。
KRAS（35%）和 BRAF（V600E）（14%）突变几乎是相互排斥的。KRAS 突变更可能发生在无结肠癌家族史和从不吸烟的患者中。KRAS 突变的肿瘤 dMMR 发生率较低（比值比[OR] = 0.21；95%置信区间[CI] = 0.15 至 0.31；P <.001）和高级别组织学（OR = 0.73；95% CI = 0.59 至 0.92；P <.001），但更倾向于右侧。在 KRAS 突变的肿瘤中，具有 Gly13Asp 突变的肿瘤倾向于具有 dMMR 和高级别组织学。BRAF（V600E）突变的肿瘤更可能发生在 70 岁或以上的患者（OR = 3.33；95% CI = 2.50 至 4.42；P <.001）和当前或曾经吸烟的患者（OR = 1.64；95% CI = 1.26 至 2.14；P <.001），但在非白人和男性中较少见。具有 BRAF（V600E）突变的肿瘤更可能位于右侧，且具有四个或更多阳性淋巴结、高级别组织学和 dMMR。
特定的患者和肿瘤特征与 KRAS 和 BRAF（V600E）突变相关。
