Genetic variations in colorectal cancer risk and clinical outcome.
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.
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
K
Zhang
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.
Jesse
J
Civan
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.
Sushmita
S
Mukherjee
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.
Fenil
F
Patel
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.
Hushan
H
Yang
D002453:Cell Cycle; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction; D016896:Treatment Outcome
Cell cycle control; Colorectal cancer; Gene desert; Genome instability; Genome-wide association study; Signal transduction pathways; Single nucleotide polymorphism