Critical review and synthesis of the epidemiologic evidence on formaldehyde exposure and risk of leukemia and other lymphohematopoietic malignancies

Recent epidemiologic studies indicate elevated risks for some lymphohematopoietic malignancies (LHM) related to formaldehyde exposure. We performed a systematic review of literature to assess the strength and consistency of associations. We summarized published literature in the PubMed database of the National Library of Medicine during 1966-2012. Literature was categorized according to study design and population: industrial cohort studies, professional cohort studies, and population-based case-control studies. Findings from occupational cohort and population-based case-control studies were very inconsistent for LHM, including myeloid leukemia. Apart from some isolated exceptions, relative risks were close to the null, and there was little evidence for dose-response relations for any of the LHM. At present, there is no consistent or strong epidemiologic evidence that formaldehyde is causally related to any of the LHM. The absence of established toxicological mechanisms further weakens any arguments for causation. To be informative, future epidemiologic research should improve on formaldehyde exposure assessment and apply modern diagnostic schemes for specific LHM.