Stigliano Vittoria, Sanchez-Mete Lupe, Martayan Aline, Anti Marcello
Vittoria Stigliano, Lupe Sanchez-Mete, Marcello Anti, Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, 00144 Rome, Italy.
World J Gastroenterol. 2014 Sep 21;20(35):12420-30. doi: 10.3748/wjg.v20.i35.12420.
Colorectal cancer is the third most common cancer diagnosed worldwide. Although epidemiology data show a marked variability around the world, its overall incidence rate shows a slow but steady decrease, mainly in developed countries. Conversely, early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%. Colorectal cancer has a substantial proportion of familial cases. In particular, early age at onset is especially suggestive of hereditary predisposition. The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group. Two distinct subtypes of early-onset colorectal cancers can be identified: a "sporadic" subtype, usually without family history, and an inherited subtype arising in the context of well defined hereditary syndromes. The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype, which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases, whereas in the "sporadic" subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants, so far largely unidentified, displaying variable penetrance. These variants are thought to act cumulatively to increase the risk of colorectal cancer, and presumably to also anticipate its onset. Efforts are ongoing in the attempt to unravel the intricate genetic basis of this "sporadic" early-onset disease. A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies.
结直肠癌是全球第三大常见诊断癌症。尽管流行病学数据显示世界各地存在显著差异，但其总体发病率呈缓慢但稳定的下降趋势，主要在发达国家。相反，早发性结直肠癌似乎呈现相反趋势，在美国和欧盟的总体患病率在3.0%至8.6%之间。结直肠癌有相当比例的家族性病例。特别是发病年龄早尤其提示遗传易感性。结直肠癌病例的临床病理和分子特征不仅在早发和晚发病例之间，而且在早发组内都表现出明显的异质性。早发性结直肠癌可分为两种不同的亚型：一种是“散发性”亚型，通常无家族史；另一种是在明确的遗传综合征背景下出现的遗传性亚型。早发性疾病的发病机制在遗传性亚型中已得到充分表征，主要与林奇综合征相关，偶尔与其他罕见的孟德尔疾病相关，而在“散发性”亚型中，疾病的起源可能归因于各种常见/罕见的基因变异，目前大多尚未确定，其外显率各不相同。这些变异被认为会累积作用以增加患结直肠癌的风险，并且可能还会提前发病时间。目前正在努力揭示这种“散发性”早发性疾病复杂的遗传基础。对分子实体和途径的更好了解可能会影响针对家庭的预防和临床管理策略。
