Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
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Morton Lindsay M, Slager Susan L, Cerhan James R, Wang Sophia S, Vajdic Claire M, Skibola Christine F, Bracci Paige M, de Sanjosé Silvia, Smedby Karin E, Chiu Brian C H, Zhang Yawei, Mbulaiteye Sam M, Monnereau Alain, Turner Jennifer J, Clavel Jacqueline, Adami Hans-Olov, Chang Ellen T, Glimelius Bengt, Hjalgrim Henrik, Melbye Mads, Crosignani Paolo, di Lollo Simonetta, Miligi Lucia, Nanni Oriana, Ramazzotti Valerio, Rodella Stefania, Costantini Adele Seniori, Stagnaro Emanuele, Tumino Rosario, Vindigni Carla, Vineis Paolo, Becker Nikolaus, Benavente Yolanda, Boffetta Paolo, Brennan Paul, Cocco Pierluigi, Foretova Lenka, Maynadié Marc, Nieters Alexandra, Staines Anthony, Colt Joanne S, Cozen Wendy, Davis Scott, de Roos Anneclaire J, Hartge Patricia, Rothman Nathaniel, Severson Richard K, Holly Elizabeth A, Call Timothy G, Feldman Andrew L, Habermann Thomas M, Liebow Mark, Blair Aaron, Cantor Kenneth P, Kane Eleanor V, Lightfoot Tracy, Roman Eve, Smith Alex, Brooks-Wilson Angela, Connors Joseph M, Gascoyne Randy D, Spinelli John J, Armstrong Bruce K, Kricker Anne, Holford Theodore R, Lan Qing, Zheng Tongzhang, Orsi Laurent, Dal Maso Luigino, Franceschi Silvia, La Vecchia Carlo, Negri Eva, Serraino Diego, Bernstein Leslie, Levine Alexandra, Friedberg Jonathan W, Kelly Jennifer L, Berndt Sonja I, Birmann Brenda M, Clarke Christina A, Flowers Christopher R, Foran James M, Kadin Marshall E, Paltiel Ora, Weisenburger Dennis D, Linet Martha S, Sampson Joshua N
Аннотация
METHODS: We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE).
RESULTS: Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10(-4)), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10(-4)). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.
CONCLUSIONS: Using a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.