Racial Differences in BRAF/KRAS Mutation Rates and Survival in Stage III Colon Cancer Patients
Racial Differences in BRAF/KRAS Mutation Rates and Survival in Stage III Colon Cancer Patients
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DOI：
10.1093/jnci/djv186
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发表时间：
2015-10-01
影响因子：
10.3
通讯作者：
Sinicrope, Frank A.
中科院分区：
文献类型：
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作者：
Yoon, Harry H.;Shi, Qian;Sinicrope, Frank A.
背景：在控制了临床病理变量和治疗后，结肠癌预后中的种族差异是否持续存在尚不清楚。在北美患者中比较亚洲人和其他种族的分子标记分析尚未见报道。方法：在一项辅助试验(Alliance N0147)中，对3305例接受FOLFOX为基础的化疗的结肠癌患者进行了BRAF(V600E)和KRAS突变分析。种族类别包括亚洲人、黑人或白人。用COX模型估计无病生存期(DFS)和复发时间(TTR)。结果：白人肿瘤的BRAF突变频率(13.9%)是亚洲人和黑人肿瘤的两倍。黑人肿瘤中KRAS基因突变率最高(44.1%)。KRAS/BRAF野生型肿瘤在亚洲人中最常见(66.7%)(P-all<；.001)。种族对预后的影响因年龄和N分期不同而不同(均为P交互作用和0.02)。与白人相比，黑人在年龄小于50岁(危险比[HR]=2.84，95%可信区间[CI]=1.73至4.66)或患有N1疾病(HR=1.54，95%CI=1.04至2.29)的患者中有较短的DFS，独立于BRAF、KRAS和其他协变量。使用TTR值作为结果，结果是一致的。结论：亚洲人结肠癌患者的BRAF和KRAS基因突变率低于黑人和白人。我们报道了在结节阳性疾病中种族与年龄和N分期的新的交互作用，表明尽管在III期试验中相同的分期和治疗，种族在存活率上的差异仍然存在。
Background: It is unknown if, after controlling for clinicopathologic variables and treatment, racial disparities in colon cancer outcomes persist. Molecular marker analysis in North American patients comparing Asians with other races has not been reported.Methods: BRAF(V600E) and KRAS mutations were analyzed in node-positive colon cancer patients (n = 3305) treated with FOLFOX-based chemotherapy in an adjuvant trial (Alliance N0147). Race categories included Asian, black, or white. Cox models were used to estimate disease-free survival (DFS) and time to recurrence (TTR). All statistical tests were two-sided.Results: BRAF mutation frequency in tumors from whites (13.9%) was twice that of tumors from Asians or blacks. KRAS mutation rates were highest in tumors from blacks (44.1%). KRAS/BRAF wild-type tumors were most common among Asians (66.7%) (P-overall < .001). The prognostic impact of race differed by age and N stage (both P-interaction < .02). Compared with whites, blacks had shorter DFS among patients younger than age 50 years (hazard ratio [HR] = 2.84, 95% confidence interval [CI] = 1.73 to 4.66) or with N1 disease (HR = 1.54, 95% CI = 1.04 to 2.29), independent of BRAF, KRAS, and other covariates. Findings were consistent using TTR as the outcome. Asians had longer DFS among N2 tumors that was partly mediated by less frequent BRAF mutation.Conclusions: Colon cancers from Asians have a lower rate of BRAF and KRAS mutations than blacks or whites. We report a novel interaction of race with age and N stage in node-positive disease, indicating that racial disparities in survival persist despite uniform stage and treatment in a phase III trial.