Objective: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations (TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods: Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated. Results: (1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC. A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion: Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.
全球早发性结直肠癌（EOCRC）的发病率呈现逐年升高趋势，但散发EOCRC的分子特征及预后风险尚不清楚。本研究利用Meta分析的方法，选择了6种常见基因突变（TP53、BRAF、KRAS、NRAS、PTEN及APC），旨在探究基因突变在散发EOCRC中的发生率及其与癌症生存的关联。 方法： 本研究利用Ovid Embase和Ovid Medline电子数据库进行检索，被研究人群为散发EOCRC患者（即确诊结直肠癌的年龄<50周岁，且未发现易患结直肠癌的遗传综合征）。利用质量评价工具对纳入的文章进行评价，利用随机效应模型和固定效应模型进行Meta分析，利用Cochran Q统计量和I2指标对异质性进行检验，以评价6种常见基因突变在散发EOCRC中的发生率以及其与癌症生存的关联。 结果： （1）散发EOCRC中特定基因突变发生率：共有34篇文献被纳入本Meta分析。APC基因突变的发生率为36%（来自13篇文献，95%CI：19%~55%，P=0.043）；KRAS基因突变的发生率为30%（来自26篇文献，95%CI：24%~35%，P=0.190）；BRAF基因突变的发生率为7%（来自18篇文献，95%CI：5%~11%，P=0.422）；NRAS基因突变的发生率为4%（来自5篇文献，95%CI：3%~5%，P=0.586）；PTEN基因突变的发生率为6%（来自6篇文献，95%CI：4%~10%，P=0.968）；TP53基因突变的发生率为59%（来自13篇文献，95%CI：49%~68%，P=0.164）。（2）基因突变与散发EOCRC的生存关联：共有6篇文献被纳入本Meta分析。EOCRC中，与野生型BRAF相比，突变型BRAF与EOCRC患者的全因死亡风险升高相关，差异有统计学意义（pooled HR=2.85，95%CI：1.45~5.60，P=0.002）。亚组分析显示，与西方人群相比，东方人群中的BRAF基因突变发生率更高，TP53、KRAS、NRAS和APC基因突变发生率更低；PTEN基因突变的发生率在不同地区人群中未见明显差异。 结论： 与总体人群发生的CRC相比，EOCRC中APC和KRAS突变的发生率更低，TP53突变的发生率基本一致。BRAF突变的EOCRC患者全因死亡风险升高。.