This article is more than 5 years old. Information may no longer be current.
All major risk genes for familial CRC now identified, researchers say
Click Here to Manage Email Alerts
Researchers from The Institute of Cancer Research in London have identified five new genes potentially associated with colorectal cancer and concluded that all major colorectal cancer risk genes have now likely been identified.
Their findings also suggest that the collective impact of common, minor DNA variations on familial CRC risk may be more significant than previously thought, as mutations in the major risk genes accounted only for up to a third of familial CRC cases.
“Our study is the largest ever conducted of the genetics of bowel cancer, and sets out a detailed map of the disease that could lead us to new ways of treating or preventing it,” Richard Houlston, MD, PhD, professor of molecular and population genetics at The Institute of Cancer Research, said in a press release. “The research closes one chapter in the study of bowel cancer, by concluding that all the major risk genes have now been found. But it opens another by underlining the importance of tracking down the many missing genetic variations which each have a very small effect alone, but together make the biggest impact on inherited risk.”
Richard Houlston
Aiming to quantify the impact of rare germline mutations in familial CRC and identify new susceptibility genes, Houlston and colleagues analyzed whole exome sequencing data from 1,006 individuals with early-onset familial CRC and 1,609 healthy controls, and performed further analyses on 5,552 cases and 6,792 controls.
They found highly penetrant rare mutations in 16% of the familial CRC cases, and while most were present in known genes, they found POT1, POLE2 and MRE11 to be candidate CRC genes. Disruptive mutations in IL12RB1 and LIMK2 were also identified. Moreover, the researchers did not identify any coding low-frequency alleles (1-5%) with moderate effect.
Further research is needed to confirm these very rare mutations, according to the press release.
However, the researchers concluded that 15% to 31% of familial CRC cases are caused by rare variants in established CRC predisposition genes and that it is unlikely that there are any additional major CRC risk genes outside of the 12 that are already established, excluding the five potential new genes identified in this study. Further, they concluded that the remaining risk must come from minor DNA variations, about 30 of which have been identified so far, and environmental factors.
“Each cancer gene that has been discovered, or common genetic variant that we will continue to uncover, provides us with new insights into the underlying biology of the disease, and increases our ability to assess people for their risk,” Paul Workman, FMedSci, FRS, chief executive of The Institute of Cancer Research, said in the press release. “This study represents an important contribution to our understanding of the genetics of bowel cancer. It provides a marker of the dramatic progress we have made so far in decoding the inherited risk of the disease, and gives us confidence that the most important risk genes have now been found.” – by Adam Leitenberger
Disclosures: The researchers report no relevant financial disclosures.
Click Here to Manage Email Alerts