Zhang Kejin, Civan Jesse, Mukherjee Sushmita, Patel Fenil, Yang Hushan
Kejin Zhang, Sushmita Mukherjee, Fenil Patel, Hushan Yang, Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, United States.
World J Gastroenterol. 2014 Apr 21;20(15):4167-77. doi: 10.3748/wjg.v20.i15.4167.
Colorectal cancer (CRC) has an apparent hereditary component, as evidenced by the well-characterized genetic syndromes and family history associated with the increased risk of this disease. However, in a large fraction of CRC cases, no known genetic syndrome or family history can be identified, suggesting the presence of "missing heritability" in CRC etiology. The genome-wide association study (GWAS) platform has led to the identification of multiple replicable common genetic variants associated with CRC risk. These newly discovered genetic variations might account for a portion of the missing heritability. Here, we summarize the recent GWASs related to newly identified genetic variants associated with CRC risk and clinical outcome. The findings from these studies suggest that there is a lack of understanding of the mechanism of many single nucleotide polymorphisms (SNPs) that are associated with CRC. In addition, the utility of SNPs as prognostic markers of CRC in clinical settings remains to be further assessed. Finally, the currently validated SNPs explain only a small fraction of total heritability in complex-trait diseases like CRC. Thus, the "missing heritability" still needs to be explored further. Future epidemiological and functional investigations of these variants will add to our understanding of CRC pathogenesis, and may ultimately lead to individualized strategies for prevention and treatment of CRC.
结直肠癌（CRC）具有明显的遗传成分，这一点已被与该疾病风险增加相关的特征明确的遗传综合征和家族史所证实。然而，在很大一部分CRC病例中，无法确定已知的遗传综合征或家族史，这表明CRC病因中存在“遗传力缺失”。全基因组关联研究（GWAS）平台已导致鉴定出多个与CRC风险相关的可重复常见遗传变异。这些新发现的遗传变异可能解释了部分遗传力缺失。在此，我们总结了近期与新鉴定的与CRC风险和临床结局相关的遗传变异有关的GWAS。这些研究的结果表明，对于许多与CRC相关的单核苷酸多态性（SNP）的机制缺乏了解。此外，SNP作为CRC临床预后标志物的效用仍有待进一步评估。最后，目前已验证的SNP仅解释了像CRC这样的复杂性状疾病中总遗传力的一小部分。因此，“遗传力缺失”仍需进一步探索。对这些变异进行未来的流行病学和功能研究将增进我们对CRC发病机制的理解，并最终可能导致CRC预防和治疗的个体化策略。
