早发型和普通型结直肠癌的全面比较。

A Comprehensive Comparison of Early-Onset and Average-Onset Colorectal Cancers.

机构信息

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

出版信息

J Natl Cancer Inst. 2021 Nov 29;113(12):1683-1692. doi: 10.1093/jnci/djab124.

DOI:10.1093/jnci/djab124

PMID:34405229

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8634406/

Abstract

BACKGROUND

The causative factors for the recent increase in early-onset colorectal cancer (EO-CRC) incidence are unknown. We sought to determine if early-onset disease is clinically or genomically distinct from average-onset colorectal cancer (AO-CRC).

METHODS

Clinical, histopathologic, and genomic characteristics of EO-CRC patients (2014-2019), divided into age 35 years and younger and 36-49 years at diagnosis, were compared with AO-CRC (50 years and older). Patients with mismatch repair deficient tumors, CRC-related hereditary syndromes, and inflammatory bowel disease were excluded from all but the germline analysis. All statistical tests were 2-sided.

RESULTS

In total, 759 patients with EO-CRC (35 years, n = 151; 36-49 years, n = 608) and AO-CRC (n = 687) were included. Left-sided tumors (35 years and younger = 80.8%; 36-49 years = 83.7%; AO = 63.9%; P < .001 for both comparisons), rectal bleeding (35 years and younger = 41.1%; 36-49 years = 41.0%; AO = 25.9%; P = .001 and P < .001, respectively), and abdominal pain (35 years and younger = 37.1%; 36-49 years = 34.0%; AO = 26.8%; P = .01 and P = .005, respectively) were more common in EO-CRC. Among microsatellite stable tumors, we found no differences in histopathologic tumor characteristics. Initially, differences in TP53 and Receptor Tyrosine Kinase signaling pathway (RTK-RAS)alterations were noted by age. However, on multivariate analysis including somatic gene analysis and tumor sidedness, no statistically significant differences at the gene or pathway level were demonstrated. Among advanced microsatellite stable CRCs, chemotherapy response and survival were equivalent by age cohorts. Pathogenic germline variants were identified in 23.3% of patients 35 years and younger vs 14.1% of AO-CRC (P = .01).

CONCLUSIONS

EO-CRCs are more commonly left-sided and present with rectal bleeding and abdominal pain but are otherwise clinically and genomically indistinguishable from AO-CRCs. Aggressive treatment regimens based solely on the age at CRC diagnosis are not warranted.

摘要

背景

近期早发性结直肠癌（EO-CRC）发病率上升的原因尚不清楚。我们试图确定早发性疾病在临床或基因组学上是否与普通发病的结直肠癌（AO-CRC）不同。

方法

将 2014 年至 2019 年期间诊断为 EO-CRC（年龄 35 岁及以下和 36-49 岁）的患者的临床、组织病理学和基因组学特征与 AO-CRC（50 岁及以上）进行比较。排除所有除种系分析以外的错配修复缺陷肿瘤、CRC 相关遗传性综合征和炎症性肠病患者。所有统计检验均为双侧检验。

结果

共纳入 759 例 EO-CRC（年龄 35 岁及以下，n=151；36-49 岁，n=608）和 AO-CRC（n=687）患者。左侧肿瘤（35 岁及以下=80.8%；36-49 岁=83.7%；AO=63.9%；两者比较 P<0.001）、直肠出血（35 岁及以下=41.1%；36-49 岁=41.0%；AO=25.9%；P=0.001 和 P<0.001）和腹痛（35 岁及以下=37.1%；36-49 岁=34.0%；AO=26.8%；P=0.01 和 P=0.005）在 EO-CRC 中更为常见。在微卫星稳定肿瘤中，我们没有发现组织病理学肿瘤特征的差异。最初，年龄差异导致 TP53 和受体酪氨酸激酶信号通路（RTK-RAS）改变。然而，在包括体细胞基因分析和肿瘤侧别在内的多变量分析中，基因或通路水平没有显示出统计学上的显著差异。在高级微卫星稳定 CRC 中，化疗反应和生存情况按年龄组相当。35 岁及以下的患者中发现致病性种系变异的比例为 23.3%，而 AO-CRC 为 14.1%（P=0.01）。