Ionising radiation as a risk factor for lymphoma: a review

The ability of ionising radiation to induce lymphoma is unclear. Here, we present a narrative review of epidemiological evidence of the risk of lymphoma, including chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM), among various exposed populations including atomic bombing survivors, industrial and medical radiation workers, and individuals exposed for medical purposes. Overall, there is a suggestion of a positive dose-dependent association between radiation exposure and lymphoma. The magnitude of this association is highly imprecise, however, with wide confidence intervals frequently including zero risk. External comparisons tend to show similar incidence and mortality rates to the general population. Currently, there is insufficient information on the impact of age at exposure, high versus low linear energy transfer radiation, external versus internal or acute versus chronic exposures. Associations are stronger for males than females, and stronger for non-Hodgkin lymphoma and MM than for Hodgkin lymphoma, while the risk of radiation-induced CLL may be non-existent. This broad grouping of diverse diseases could potentially obscure stronger associations for certain subtypes, each with a different cell of origin. Additionally, the classification of malignancies as leukaemia or lymphoma may result in similar diseases being analysed separately, while distinct diseases are analysed in the same category. Uncertainty in cell of origin means the appropriate organ for dose response analysis is unclear. Further uncertainties arise from potential confounding or bias due to infectious causes and immunosuppression. The potential interaction between radiation and other risk factors is unknown. Combined, these uncertainties make lymphoma perhaps the most challenging malignancy to study in radiation epidemiology.