Colorectal cancer is one of the most common cancers in the United States, but what many people don’t realize is that it affects more men than women. During a recent study, researchers determined that this increased risk in men could be the result of an aberration in a sex chromosome, making this the first time that a sex chromosome has been associated with the development of a form of cancer that can affect both genders.
Researchers from the Institute of Cancer Research, Edinburgh University and the University of Oxford contributed to the international collaborative study, hoping to find changes in the DNA code associated with an increased risk of colorectal cancer development. What they found was a faulty region of the x-chromosome, which is one of the two chromosomes that determine gender.
The Genetic Link
This faulty region results from reduced levels of SHROOM2, a gene that has a role in the development of cells and has previously been connected to cancer. In women, who have two x-chromosomes, this faulty region in one chromosome is masked by the correctly-functioning region in the other. But there is no second x-chromosome to hide the aberration in men. This may help to explain why men are at a higher risk for colorectal cancer.
The researchers used data from five other international studies concerning pieces of DNA called single nucleotide polymorphisms (SNPs) which vary from person to person. In doing this they attempted to identify SNPs that were more common in individuals with cancer. They also identified two additional risk variants, the first of which is CDK1NA, a gene that prevents the development of the new DNA strands that cancer cells need for growth and division, as well as codes for a protein that controls the pathways that suppress tumors in cells. The second is POLD3, a gene that assists with two DNA-repairing pathways that may be defective in some cases of colorectal cancer.
New Hope for Screening and Treatment
With the x-chromosome link and these two additional risk variants, the total number of regions on the genome now known to increase the risk of colorectal cancer has risen to 20. Researchers hope that these discoveries will help them to better target colorectal cancer screening in those individuals who may be at a higher risk. In addition, they believe that a more complete understanding of the genetic role in colorectal cancer could lead to new forms of treatment for the disease.