California and Arizona researchers have identified a gene variant that carries nearly twice the risk of developing an increasingly common type of blood cancer, according to a study published online today by the science journal Nature Genetics.
Investigators at the University of California, Berkeley (UC Berkeley) and at the Translational Genomics Research Institute (TGen) found that mutations in a gene called C6orf15, or STG, are associated with the risk of developing follicular lymphoma. This is a cancer of the body's disease-fighting network whose rates have nearly doubled in the past three decades.
In the first genome-wide association study of non-Hodgkin lymphoma, scientists at UC Berkeley and TGen identified a SNP - a single nucleotide polymorphism - that could determine susceptibility to follicular lymphoma. The SNP, a DNA variant within the more than 3-billion base pairs in the human genome, was identified as rs6457327.
The study was led by Dr. Christine Skibola, Associate Adjunct Professor of Environmental Health Sciences at UC Berkeley's School of Public Health, and by Dr. Kevin M. Brown, an Associate Investigator in the Integrated Cancer Genomics Division of TGen, a Phoenix-based, non-profit biomedical research institute.
"What's exciting about this study is that we found a target in the genome influencing the susceptibility to follicular lymphoma, which helps us discern between three major types of lymphomas," said Skibola, the paper's co-lead author. "That had not been done before on a genome-wide scale. It is our hope that this research may some day be useful in helping develop prevention, early detection and treatment of this disease."
Follicular lymphoma accounts for as much as 30 percent of all non-Hodgkin lymphoma, a cancer of the lymphatic system involving the blood, bone marrow and lymph nodes. In NHL, tumors develop in lymphocytes, a type of white blood cell. Follicular lymphoma arises from B-cells, a specific type of white blood cell. NHL is the fifth most common type of cancer in the U.S., and is newly diagnosed in about 66,000 Americans each year, and annually kills nearly 20,000, according to the National Cancer Institute.
Researchers found that, for SNP rs6457327, the presence of the G allele - a DNA letter that varies within the genome - was protective against follicular lymphoma, while the presence of the A allele was predictive of an increased risk of developing follicular lymphoma. Dr. Brown said individuals who had the A variant were nearly twice as likely to develop follicular lymphoma.
"There's clearly a genetic component to the disease. The hope is to one day be able to take these results, combine them with other tests, and turn them into an individualized assessment of disease risk,'' said Dr. Brown, the study's other co-lead author. "This is a starting point.''
Dr. Skibola said more studies would be needed to determine the biological importance of other STG SNPs linked to rs6457327 that might change the function of the gene. This could help determine how they might influence risk of the disease.
The scientists also want to know if genetic susceptibility to follicular lymphoma is associated with: