Unraveling the interactions between environmental factors and genetic polymorphisms in non-Hodgkin lymphoma risk

The etiologic causes for non-Hodgkin lymphoma (NHL) remain largely unexplained. Challenges include the heterogeneous nature of NHL, the difficulty in accurately assessing exposures and the few genetic variations with confirmed associations to date, with none yet identified as causal. These challenges are compounded when evaluating gene-environment interactions. However, there are some well-characterized NHL risk factors where pursuing gene-environment interactions could shed important information on the mechanisms relevant for lymphomagenesis, such as whether common mechanisms of action exist across different exposures, specific gene families or pathways are of importance for certain exposures, or susceptible subgroups can be identified. As new associations from genome-wide association studies are confirmed, broader agnostic and data-mining approaches may yield additional clues. These results could provide a platform for identifying biological mechanisms of interest and identifying new and/or clarifying known exposures important for lymphomagenesis. This will require large consortial efforts to attain adequate sample size and power to detect meaningful biological and statistical interactions.