Gene variant linked to higher risk of non-Hodgkin lymphoma
| 20 July 2009
BERKELEY — Researchers have identified a gene variant that carries nearly twice the risk of developing an increasingly common type of non-Hodgkin lymphoma, a group of cancers that develops in the immune system's white blood cells.
In a study led by investigators at the University of California, Berkeley, and at the Translational Genomics Research Institute (TGen) in Arizona, a common variant in a gene called C6orf15, or STG, was linked to susceptibility to follicular lymphoma, which accounts for 20 to 30 percent of all non-Hodgkin lymphoma cases.
It is the first genome-wide association study of non-Hodgkin lymphoma. The mutation, a single nucleotide polymorphism (SNP) called rs6457327, was found among the more than 3 billion base pairs in the human genome.
The results are to be published July 20 in the journal Nature Genetics.
"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 study co-lead author Christine F. Skibola, an associate adjunct professor of environmental health sciences at UC Berkeley's School of Public Health. "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."
Non-Hodgkin lymphoma, the fifth most common type of cancer in the United States, is newly diagnosed in about 66,000 Americans each year, and annually kills nearly 20,000, according to the National Cancer Institute. Overall, the annual incidence of non-Hodgkin lymphoma has doubled since the 1970s, and is the most common type of blood cancer in the United States.
The researchers looked at variations in the gene and found that the presence of the G allele of SNP rs6457327 was actually protective against follicular lymphoma, occurring less frequently among people with the cancer. In contrast, the presence of the A allele was predictive of an increased risk of developing follicular lymphoma. Brown said individuals who had the A allele 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 the study's co-lead author Kevin M. Brown, an associate investigator in the Integrated Cancer Genomics Division of TGen, a non-profit biomedical research institute based in Phoenix, Ariz. "This is a starting point."
Skibola said more studies would be needed to determine the biological importance of other mutations 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 said future studies should further investigate whether genetic susceptibility to follicular lymphoma is associated with:
- Environmental factors, such as exposure to the sun
- Conditions such as psoriasis, a chronic, autoimmune skin disease closely associated with a similar region of the genome
- Exposure to viruses. Follicular lymphoma is associated with HIV infection, occurring in as many as 10 percent of all HIV-positive patients, according to the Lymphoma Research Foundation.
The analysis was conducted using DNA from population-based, non-Hodgkin lymphoma case-control studies led by researchers from UC San Francisco. Follow-up validation studies included independent case-control studies from Canada and Germany.
To reduce the potential for complicating factors, the more than 3,000 samples in the UC Berkeley-TGen study were from individuals who were HIV negative. Brown said future studies could include HIV-positive individuals, if enough samples were made available.
The pooled genome-wide association study used by the UC Berkeley-TGen investigators allowed them to screen more than 500,000 SNPs. The nearly 90 most significant SNPs were then genotyped to more closely examine their association with lymphoma.
This same pooling technique has been pioneered by TGen to screen for genes in other studies. Additional collaborations between UC Berkeley and TGen are planned.
Other co-authors of the study include researchers from UC Berkeley, UC San Francisco, the International Computer Science Institute in Berkeley, the British Columbia Cancer Agency in Canada, and the German Cancer Research Center in Germany.