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Lymphoma is a type of cancer in which immune cells called lymphocytes undergo uncontrolled cell division and form a solid tumor in lymphoid organs, such as the lymph nodes or the spleen. Through an international collaborative genome-wide association study, Jianjun Liu at the A*STAR Genome Institute of Singapore and co-workers have now identified two genetic variants, known as single nucleotide polymorphisms (SNPs), on chromosome 6 that increase the risk of developing lymphoma.
In a previous genome-wide association study, the researchers identified rs10484561 as an SNP on chromosome 6 that increases the risk of developing follicular lymphoma, a type of lymphoma in which tumors grow as spherical structures called follicles. This time, using a larger, independent sample of follicular lymphoma patients and controls from Denmark and Sweden, Liu and his co-workers identified another SNP called rs2647012 on the same small portion of chromosome 6 as rs10484561. Unlike rs10484561, however, rs2647012 actually decreases the risk of developing follicular lymphoma.
Both SNPs are located within a genomic region that encodes human leukocyte antigen (HLA) proteins, which present foreign antigens to other immune cells and mold the immune response. The researchers suggest that the SNPs they found may affect HLA expression or the binding affinity of HLA proteins to foreign antigens. This could lead to cancer by modulating how foreign antigens activate the immune system, allowing for uncontrolled proliferation of immune cells. Alternatively, the SNPs may affect the efficiency of the immune response against tumor cells.
“By analyzing how the two SNPs are inherited in the population, we realized that both must have appeared within distinct evolutionary lineages in the study population,” says Liu. “Therefore, each SNP will influence the risk of developing the cancer independently.”
The researchers also studied the effects of these SNPs on other types of lymphoma. They found that rs10484561 increased the risk of developing diffuse large B-cell lymphoma, a cancer of lymphocytes called B cells. The observation of a link between the same genetic SNP and more than one type of lymphoma suggested to the researchers that the mechanisms that induce these types of lymphoma may somehow overlap. The findings therefore indicate that these different lymphoma subtypes may share a common treatment.
“Having identified the genetic risk factors in Europeans in this study, we next plan to test if they influence lymphoma risk in Singaporeans,” says Liu, who is now collaborating with the Singapore lymphoma study.
The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore.
