The continuing search for predisposing colorectal cancer variants

Area of Science:

• Genetics
• Oncology
• Cancer Research

Background:

• High-penetrance mutations in specific genes cause colorectal cancer (CRC) in high-risk families.
• The genetic architecture of sporadic CRC is less understood, with recent genome-wide association studies (GWAS) beginning to elucidate its complexity.
• Ten genetic loci have been associated with increased CRC risk to date.

Purpose of the Study:

• To summarize the current understanding of the genetic factors contributing to colorectal cancer (CRC).
• To highlight the shift in research focus from common variants to less common and unclassified genetic variants for sporadic CRC.
• To underscore the significant portion of the genetic contribution to CRC that remains unknown.

Main Methods:

• Review of multicentric genome-wide association studies (GWAS) for colorectal cancer (CRC).
• Analysis of identified genetic loci associated with CRC risk.
• Discussion of the evolving search for genetic variants, including common, less common, and unclassified types.

Main Results:

• Ten genetic loci have been associated with an increased risk of colorectal cancer (CRC).
• The search for common, low-penetrance variants in European populations is largely complete.
• Research is now concentrating on less common variants with higher penetrance and unclassified variants of unknown significance.

Conclusions:

• While high-penetrance mutations explain CRC in some families, sporadic cases require further genetic investigation.
• Less than 10% of the known 35% genetic contribution to CRC has been identified.
• Future research should focus on less common variants and unclassified genetic factors to fully understand CRC's genetic basis.