title: Non-Hodgkin Lymphoma, Body Mass Index, and Cytokine Polymorphisms: A Pooled Analysis from the InterLymph Consortium.
abstract: BACKGROUND
  Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms, and selected mature B-cell neoplasms is reported.
  
  
  METHODS
  Data on 4,979 cases and 4,752 controls from nine American/European studies from the InterLymph consortium (1988-2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).
  
  
  RESULTS
  Obesity (BMI ≥ 30 kg/m(2)) was associated with DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02-1.73], as was TNF-308GA+AA (OR = 1.24; 95% CI, 1.07-1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost 2-fold relative to those of normal weight and TNF-308GG (OR = 1.93; 95% CI, 1.27-2.94), with a RERI of 0.41 (95% CI, -0.05-0.84; Pinteraction = 0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.
  
  
  CONCLUSIONS
  Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk.
  
  
  CONCLUSIONS
  Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma.
authors.affiliation: Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, United Kingdom. eleanor.kane@ecsg.york.ac.uk.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Kane
authors.affiliation: Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, Alabama.
authors.forename: Christine F
authors.initials: CF
authors.lastname: Skibola
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Paige M
authors.initials: PM
authors.lastname: Bracci
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, IDIBELL, and CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Costas
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin Ekström
authors.initials: KE
authors.lastname: Smedby
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Holly
authors.affiliation: Biological Hematology Unit, CRB Ferdinand Cabanne, University Hospital of Dijon and University of Burgundy, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Maynadié
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Novak
authors.affiliation: Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, United Kingdom.
authors.forename: Tracy J
authors.initials: TJ
authors.lastname: Lightfoot
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.affiliation: Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, United Kingdom.
authors.forename: Alex G
authors.initials: AG
authors.lastname: Smith
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mark
authors.initials: M
authors.lastname: Liebow
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.affiliation: Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Morton
authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, IDIBELL, and CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.affiliation: Department of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, California.
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, United Kingdom.
authors.forename: Eve
authors.initials: E
authors.lastname: Roman
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D042583:Lymphangiogenesis / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D016207:Cytokines; D004273:DNA, Neoplasm