Venugopal Anand, Stoffel Elena M
Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
Rogel Cancer Center, University of Michigan, Ann Arbor, USA.
Curr Treat Options Gastroenterol. 2019 Mar;17(1):89-98. doi: 10.1007/s11938-019-00219-4.
Routine screening for colorectal cancer (CRC) in adults > 50 years of age has led to overall reductions in CRC incidence and CRC-related mortality. Yet CRC incidence among young adults age < 50 continues to increase without a clear explanation. This review examines the changing epidemiology of CRC and emerging evidence regarding the influence of genetic and lifestyle factors on risk for colorectal neoplasia.
Young-onset CRC (yCRC), defined as CRC diagnosed in individuals younger than age 50, is a heterogeneous disease. Approximately, one in every five individuals affected with yCRC carries a pathogenic germline variant in genes associated with predisposition to cancer. However, most have no clinically identifiable risk factors. Analyses of birth cohorts estimate CRC risk among millennials to be 2-4 times higher than their grandparents', suggesting that changes in health behaviors and environmental factors are having an impact on CRC risk. Young individuals with CRC tend to be diagnosed at later stages and often present with metastatic disease. yCRC tumors arise predominantly in the distal colon and are more likely than older-onset tumors to exhibit microsatellite and chromosome stable (MACS) phenotypes. Although yCRC patients are more likely than their older counterparts to be treated with multimodality chemotherapy regimens, more aggressive treatments have not yielded measurable survival gains. Since one in ten new CRC diagnoses involve individuals age < 50, recent guidelines have proposed lowering the age for average risk CRC screening from 50 to 45; however, further studies are needed to evaluate testing strategies based on individuals' age and risk. Significant shifts in CRC epidemiology and diversity of tumor phenotypes support genetic and environmental factors as modifiers of cancer risk. Emerging data correlating tumor molecular features with outcomes justify further investigation into mechanisms of carcinogenesis to elucidate how specific factors (inherited and/or acquired) might stimulate young-onset colorectal neoplasia.
对50岁以上成年人进行结直肠癌（CRC）的常规筛查已使CRC发病率和CRC相关死亡率总体下降。然而，50岁以下年轻人的CRC发病率持续上升，原因尚不明确。本综述探讨了CRC流行病学的变化以及关于遗传和生活方式因素对结直肠肿瘤发生风险影响的新证据。
青年发病的CRC（yCRC）定义为在50岁以下个体中诊断出的CRC，是一种异质性疾病。约五分之一的yCRC患者携带与癌症易感性相关基因的致病性种系变异。然而，大多数患者没有临床可识别的风险因素。对出生队列的分析估计，千禧一代患CRC的风险比他们的祖父母高2至4倍，这表明健康行为和环境因素的变化正在影响CRC风险。患有CRC的年轻人往往在较晚阶段被诊断出来，且常表现为转移性疾病。yCRC肿瘤主要发生在结肠远端，比老年发病的肿瘤更可能表现出微卫星和染色体稳定（MACS）表型。尽管yCRC患者比老年患者更可能接受多模式化疗方案治疗，但更积极的治疗并未带来可衡量的生存获益。由于十分之一的新CRC诊断涉及50岁以下个体，最近的指南建议将平均风险CRC筛查的年龄从50岁降至45岁；然而，需要进一步研究以评估基于个体年龄和风险的检测策略。CRC流行病学的显著变化和肿瘤表型的多样性支持遗传和环境因素作为癌症风险的调节因素。将肿瘤分子特征与预后相关的新数据证明有必要进一步研究致癌机制，以阐明特定因素（遗传和/或获得性）如何可能刺激青年发病的结直肠肿瘤形成。
