A case-control study of tobacco use and other non-occupational risk factors for lymphoma subtypes defined by t(14;18) translocations and bcl-2 expression

We re-evaluated reported associations between tobacco use and other factors and non-Hodgkin lymphoma (NHL) t(14; 18)-subtypes based on fluorescence in situ hybridization (FISH) assays believed to be more sensitive than polymerase chain reaction (PCR), previously used for detecting t(14; 18). Commercial FISH assays and bcl-2 immunostaining were performed on paraffin sections to determine t(14; 18) and bcl-2 case-subtypes. Polytomous logistic regression models estimated associations between NHL case-subtypes (versus 1,245 population-based controls) and tobacco use as well as other factors. Adjusting for age, state, and proxy status, t(14; 18)-negative NHL was associated with any tobacco use (vs. no tobacco use, OR = 1.9, 95% CI = 1.0-3.5), including current smoking (vs. no cigarette use, OR = 1.9, 95% CI = 1.1-3.2). Tobacco exposures were not clearly associated with t(14; 18)-positive NHL or bcl-2 case-subtypes. Hair-dye use and family history of a hemolymphatic cancer were associated with t(14; 18)-negative NHL, but the number of exposed cases was small. The association between t(14; 18)-negative NHL and cigarette smoking was unexpected given previous evidence of associations between smoking and follicular lymphoma (which is largely t(14; 18)-positive). Future studies characterizing additional molecular characteristics of t(14; 18)-negative NHL may help determine whether the association with smoking may have been causal versus an artifact of chance or bias.