Occupational exposure to formaldehyde and risk of lymphoma subtypes: results of a multicentre Italian case-control study

Background: The International Agency for Research on Cancer classifies formaldehyde as a human carcinogen, with sufficient evidence for nasopharyngeal cancer and leukaemia. However, the association with lymphoma subtypes has been less thoroughly investigated. We explored this link in an Italian multicentre case-control study. Methods: A total of 867 incident lymphoma cases, histologically confirmed using the WHO classification, and 774 controls participated in the study. Occupational experts classified the probability, frequency, and intensity of exposure to formaldehyde for each study subject based on detailed questionnaire data and literature information. We used unconditional regression analysis to model the risk of lymphoma and its main subgroups and subtypes associated with different formaldehyde exposure metrics, adjusting for age, gender, education, and study centre. Results: Ever exposure to formaldehyde was not associated with risk of all lymphomas combined, the non-Hodgkin lymphoma (NHL) and B-cell lymphoma (BCL) subgroups, or the most prevalent BCL subtypes, but multiple myeloma (MM) (OR = 2.0, 95% CI 1.19–3.31). MM risk also showed consistent upward trends with all the exposure metrics (p for trend ranging 0.005–0.034). Hodgkin’s lymphoma risk was also elevated in the top categories of intensity, duration, and cumulative exposure, but no significant increasing trends were observed. Conclusions: Our findings suggest an increased risk of multiple myeloma associated with occupational exposure to formaldehyde. A stronger link was observed for daily exposure lasting 20 years or more. The risk of Hodgkin’s lymphoma was also elevated at high exposure intensities.