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World J Gastroenterol. Apr 21, 2014; 20(15): 4167-4177
Published online Apr 21, 2014. doi: 10.3748/wjg.v20.i15.4167
Genetic variations in colorectal cancer risk and clinical outcome
Kejin Zhang, Jesse Civan, Sushmita Mukherjee, Fenil Patel, Hushan Yang
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
Kejin Zhang, College of Life Science, Northwest University, Xi'an 710069, Shaanxi Province, China
Jesse Civan, Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, United States
Author contributions: All the authors were involved in literature review and manuscript writing.
Supported by A start-up grant from Thomas Jefferson University; and National Cancer Institute Grant, CA162201
Correspondence to: Hushan Yang, PhD, Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, 111 S 11th St, Philadelphia, PA 19107, United States. hushan.yang@jefferson.edu
Telephone: +1- 215-5036521 Fax: +1-215-5039506
Received: September 28, 2013
Revised: January 8, 2014
Accepted: March 6, 2014
Published online: April 21, 2014
Processing time: 201 Days and 8.5 Hours
Abstract

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.

Keywords: Colorectal cancer; Genome-wide association study; Single nucleotide polymorphism; Signal transduction pathways; Cell cycle control; Gene desert; Genome instability

Core tip: This review covers the recent advances in genome-wide association studies (GWASs) that have identified genetic variants associated with an altered risk of colorectal cancer (CRC). In this review, we summarize single nucleotide polymorphisms (SNPs) located in or near genes that play crucial roles in signal transduction pathways, genome stability, cell cycle control, and gene expression and regulation. SNPs that are found in gene desert regions are also discussed. The relationship between genetic variations and clinical outcomes in CRC is presented from epidemiological studies that have identified SNPs with methods other than GWASs.