Patient and Tumor Characteristics and BRAF and KRAS Mutations in Colon Cancer, NCCTG/Alliance N0147
Patient and Tumor Characteristics and BRAF and KRAS Mutations in Colon Cancer, NCCTG/Alliance N0147
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DOI：
10.1093/jnci/dju106
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发表时间：
2014-07-01
影响因子：
10.3
通讯作者：
McWilliams, Robert R.
中科院分区：
文献类型：
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作者：
Gonsalves, Wilson I.;Mahoney, Michelle R.;McWilliams, Robert R.
背景 KRAS 和 BRAF(V600E) 突变分别是结肠癌重要的预测和预后标志物，但对其相关的患者和临床因素知之甚少。 方法 N0147 III 期结肠癌 III 期辅助试验中的 3397 名患者中有 2326 名患者完成了患者问卷调查。评估原发性肿瘤的 KRAS 和 BRAF(V600E) 突变以及缺陷错配修复 (dMMR) 状态。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。所有统计检验都是双向的。结果 KRAS (35%) 和 BRAF(V600E) (14%) 突变几乎是相互排斥的。 KRAS 突变更有可能出现在没有结肠癌家族史且从不吸烟的患者中。具有 KRAS 突变的肿瘤不太可能出现 dMMR（优势比 [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），但更常见于右侧。在 KRA 突变肿瘤中，具有 Gly13Asp 突变的肿瘤往往具有 dMMR 和高级别组织学。携带 BRAF(V600E) 突变的肿瘤更有可能出现在 70 岁或以上的患者 (OR = 3.33; 95% CI = 2.50 至 4.42; P < .001) 和当前或曾经吸烟者 (OR = 1.64; 95% CI = 1.26 至 2.14; P < .001) 中，但在非白人和白人中出现的可能性较小。男人。具有 BRAF(V600E) 突变的肿瘤更有可能位于右侧，并且有四个或更多阳性淋巴结、高级别组织学和 dMMR。 结论 特定的患者和肿瘤特征与 KRAS 和 BRAF(V600E) 突变相关。
Background 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.Methods 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.Results 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 KRA-Smutated 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.Conclusions Specific patient and tumor characteristics are associated with KRAS and BRAF(V600E) mutations.