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Genome Institute of Singapore-Led Team IDs Follicular Lymphoma Susceptibility SNP

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Non-Hodgkin lymphomas are a diverse set of hematological malignancies that collectively comprise the most prevalent form of blood cancer. While previous epidemiological and familial studies have shown a genetic influence on susceptibility to diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma — which are all non-Hodgkin lymphomas — an international team led by investigators at the Genome Institute of Singapore recently identified a unique SNP that suggests shared biological mechanisms of susceptibility between two common types of non-Hodgkin lymphomas.

In a three-stage genome-wide association study of follicular lymphoma in 5,877 total non-Hodgkin lymphoma patients and 6,761 controls — all of European descent — the Genome Institute of Singapore researchers and their colleagues in Australia, Canada, Denmark, Sweden, and the US validated a previously reported susceptibility SNP within the human leukocyte antigen class II region on chromosome 6p21.3 and identified another variant significantly associated with follicular lymphoma as well as diffuse large B-cell lymphoma that is 962 base pairs away.

Study co-author Jianjun Liu, associate director of human genetics at the Genome Institute of Singapore, says that his team's GWAS, which was published in PLoS Genetics in April, substantiates the association between HLA class II loci and follicular lymphoma susceptibility, and suggests a molecular link between follicular lymphoma and diffuse large B-cell lymphoma.

"Our findings [also] indicate that the differences in non-Hodgkin lymphoma risk may reside in genes encoding important components of the immune system," Liu says, referring to major histocompatibility complexes. "Moreover, some genetic risk factors are specific to one subtype, while others are shared among two or more subtypes of NHL."

The Singapore Cancer Registry indicates that lymphoma is the eighth most common cancer affecting men in the country, and notes that both incidence and mortality are on the rise. Because of this, Liu and his colleagues are eager to extend their GWAS to a Singaporean population to assess the significance of the susceptibility SNPs they identified in the European cohort. "This knowledge, combined with other findings on environmental risk factors of NHL, can be used for the identification of individuals at high risk of developing the disease," Liu says.

Ultimately, he adds, identifying at-risk individuals early could enable physicians to provide "early monitoring, advice, and treatment to these individuals." And as the non-Hodgkin lymphoma susceptibility SNPs his team identified map to a region that has also shown associations with autoimmune diseases such as rheumatoid arthritis and Sjögren syndrome, Liu says "it would be interesting to investigate whether some risk variants are shared" among them.

In the meantime, however, Liu and his colleagues "are trying to fine-map the association we identified and further identify the causal variant responsible for the observed association," he says.

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