■观察到的早发性结直肠癌(EOCRC)发病率的增加是由散发性病例驱动的,但是这些肿瘤的分子特征还没有完全了解。我们的目的是调查微卫星不稳定性(MSI)的患病率和在零星的EOCRC中选择的突变,以及他们与生存的联系。
■首先,我们在一项基于人群的队列研究中比较了北爱尔兰652例II期和III期结肠癌患者的分子特征和生存率,比较散发性早发(<50岁,n=35)年龄较大(60-69岁,n=179)患者。其次,对报告MSI患病率的研究的系统评价,错配修复缺陷(dMMR),或者BRAF,KRAS,NRAS,PIK3CA,并在散发性EOCRC中进行TP53突变。进行荟萃分析以计算散发性EOCRC中分子特征患病率的汇总估计值。
■首先,在队列研究中,与60至69岁的患者相比,EOCRC患者的结直肠癌特异性死亡风险没有显着增加(调整后的风险比1.20;95%置信区间[CI]0.61-2.39)。第二,32项研究纳入系统评价。汇总分析估计,零星EOCRC中MSI高/dMMR的患病率为10%(95%CI7%-14%)。BRAF和KRAS突变的患病率分别为1%(95%CI0%-3%)和32%(95%CI23%-40%),分别。
■散发性EOCRC的分子特征不同于老年人的癌症,特别是关于降低BRAF突变的患病率。百分之十的零星EOCRC显示MSI高/dMMR。需要进一步的研究来解决散发性EOCRC病例的生存以及分子谱是否影响该患者组的EOCRC结局。
UNASSIGNED: The observed increase in the incidence of early-onset colorectal cancer (EOCRC) is being driven by sporadic cases, but the molecular characteristics of these tumors are not fully understood. Our objective was to investigate the prevalence of microsatellite instability (MSI) and selected mutations in sporadic EOCRC, and their association with survival.
UNASSIGNED: Firstly, we compared the prevalence of molecular characteristics and survival within a population-based cohort study of 652 stage II and III colon cancer patients in Northern Ireland, comparing sporadic early-onset (<50 years, n = 35) with older (60-69 years, n = 179) patients. Secondly, a systematic review for studies reporting the prevalence of MSI, mismatch repair deficiency (dMMR), or BRAF, KRAS, NRAS, PIK3CA, and TP53 mutations in sporadic EOCRC was conducted. A meta-analysis was performed to calculate pooled estimates of the prevalence of molecular features in sporadic EOCRC.
UNASSIGNED: Firstly, within the cohort study, EOCRC patients did not have a significantly increased risk of colorectal cancer-specific death (adjusted hazard ratio 1.20; 95% confidence interval [CI] 0.61-2.39) compared with 60- to 69-year-olds. Second, 32 studies were included in the systematic review. The pooled analysis estimated a prevalence of 10% (95% CI 7%-14%) for MSI high/dMMR in sporadic EOCRC. BRAF and KRAS mutations had a prevalence of 1% (95% CI 0%-3%) and 32% (95% CI 23%-40%), respectively.
UNASSIGNED: The molecular characteristics of sporadic EOCRC differ from those of cancers in older adults, particularly regarding reduced prevalence of BRAF mutations. Ten percent of sporadic EOCRC display MSI high/dMMR. Further studies are needed to address survival in sporadic EOCRC cases and whether molecular profiles influence EOCRC outcomes in this patient group.