Approved Research

Genetics of Lymphomas

Lay summary

Lymphomas are cancers that arise from lymphatic tissues (most commonly lymph nodes) or in the lymphatic cells from other organs. They are made of many different subtypes, and as a group are one of the more common cancers in Europe and North America. Lymphomas can cluster in families, and a family history of lymphoma is an established risk factor for developing a lymphoma in the general population. However, we have only just begun to identify inherited genetic loci associated with lymphoma risk. To date, genome-wide association studies have identified multiple genetic variants that are common in the population and that are associated with lymphoma risk (or risk of a specific lymphoma subtype), although each variant has a very small effect on risk. In contrast, there has been relatively little research focused on exploring genetic variants that are low frequency or rare in the population, but have a larger effect on risk, like BRCA1 and BRCA2 in breast cancer risk. We aim to investigate the role of inherited rare and low frequency variants in lymphoma risk overall, as well as in common lymphoma subtypes, and in the context of common genetic variation. We will use a rigorous, multi-stage design with a discovery stage of lymphoma cases and controls from our own studies with independent validation in the UK Biobank to identify genetic loci associated with risk. These results should have major implications for understanding the underlying genetic epidemiology and biology of lymphoma. Lymphoma patients may benefit from targeted therapy given a mutation in a biologically relevant gene. Family members of lymphoma patients with a genetic variant may benefit from genetic testing to understand their subsequent risk of lymphoma. The expected completion time for this project is 3 years.