TY - JOUR

T1 - Etiologic heterogeneity among non-hodgkin lymphoma subtypes

T2 - The interLymph non-hodgkin lymphoma subtypes project

AU - Morton, Lindsay M.

AU - Slager, Susan L.

AU - Cerhan, James R.

AU - Wang, Sophia S.

AU - Vajdic, Claire M.

AU - Skibola, Christine F.

AU - Bracci, Paige M.

AU - de Sanjosé, Silvia

AU - Smedby, Karin E.

AU - Chiu, Brian C.H.

AU - Zhang, Yawei

AU - Mbulaiteye, Sam M.

AU - Monnereau, Alain

AU - Turner, Jennifer J.

AU - Clavel, Jacqueline

AU - Adami, Hans Olov

AU - Chang, Ellen T.

AU - Glimelius, Bengt

AU - Hjalgrim, Henrik

AU - Melbye, Mads

AU - Crosignani, Paolo

AU - di Lollo, Simonetta

AU - Miligi, Lucia

AU - Nanni, Oriana

AU - Ramazzotti, Valerio

AU - Rodella, Stefania

AU - Costantini, Adele Seniori

AU - Stagnaro, Emanuele

AU - Tumino, Rosario

AU - Vindigni, Carla

AU - Vineis, Paolo

AU - Becker, Nikolaus

AU - Benavente, Yolanda

AU - Boffetta, Paolo

AU - Brennan, Paul

AU - Cocco, Pierluigi

AU - Foretova, Lenka

AU - Maynadié, Marc

AU - Nieters, Alexandra

AU - Staines, Anthony

AU - Colt, Joanne S.

AU - Cozen, Wendy

AU - Davis, Scott

AU - de Roos, Anneclaire J.

AU - Hartge, Patricia

AU - Rothman, Nathaniel

AU - Severson, Richard K.

AU - Holly, Elizabeth A.

AU - Call, Timothy G.

AU - Feldman, Andrew L.

AU - Habermann, Thomas M.

AU - Liebow, Mark

AU - Blair, Aaron

AU - Cantor, Kenneth P.

AU - Kane, Eleanor V.

AU - Lightfoot, Tracy

AU - Roman, Eve

AU - Smith, Alex

AU - Brooks-Wilson, Angela

AU - Connors, Joseph M.

AU - Gascoyne, Randy D.

AU - Spinelli, John J.

AU - Armstrong, Bruce K.

AU - Kricker, Anne

AU - Holford, Theodore R.

AU - Lan, Qing

AU - Zheng, Tongzhang

AU - Orsi, Laurent

AU - Dal Maso, Luigino

AU - Franceschi, Silvia

AU - La Vecchia, Carlo

AU - Negri, Eva

AU - Serraino, Diego

AU - Bernstein, Leslie

AU - Levine, Alexandra

AU - Friedberg, Jonathan W.

AU - Kelly, Jennifer L.

AU - Berndt, Sonja I.

AU - Birmann, Brenda M.

AU - Clarke, Christina A.

AU - Flowers, Christopher R.

AU - Foran, James M.

AU - Kadin, Marshall E.

AU - Paltiel, Ora

AU - Weisenburger, Dennis D.

AU - Linet, Martha S.

AU - Sampson, Joshua N.

PY - 2014/8

Y1 - 2014/8

N2 - Background: Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes. 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 (PNODE). 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 (PNODE < 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 (PNODE < 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.

AB - Background: Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes. 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 (PNODE). 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 (PNODE < 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 (PNODE < 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.

UR - http://www.scopus.com/inward/record.url?scp=84906833192&partnerID=8YFLogxK

U2 - 10.1093/jncimonographs/lgu013

DO - 10.1093/jncimonographs/lgu013

M3 - Journal article

C2 - 25174034

AN - SCOPUS:84906833192

SP - 130

EP - 144

JO - Journal of the National Cancer Institute. Monographs

JF - Journal of the National Cancer Institute. Monographs

SN - 1052-6773

IS - 48

ER -