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Non-Hodgkin lymphoma, body mass index and cytokine polymorphisms: a pooled analysis from the InterLymph consortium
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Details:
  • Pubmed ID:
    25962811
  • Pubmed Central ID:
    PMC4490950
  • Funding:
    5R01 CA69669-02/CA/NCI NIH HHS/United States
    CA154643/CA/NCI NIH HHS/United States
    CA62006/CA/NCI NIH HHS/United States
    HHSN261201000140C/CA/NCI NIH HHS/United States
    N01 PC065064/PC/NCI NIH HHS/United States
    N01 PC067008/PC/NCI NIH HHS/United States
    N01 PC067009-025/CN/NCI NIH HHS/United States
    N01 PC067010/PC/NCI NIH HHS/United States
    NCI 263-MQ-701711/PHS HHS/United States
    P30 CA015083/CA/NCI NIH HHS/United States
    P50 CA097274/CA/NCI NIH HHS/United States
    P50CA97274/CA/NCI NIH HHS/United States
    R01 CA045614/CA/NCI NIH HHS/United States
    R01 CA045614-06/CA/NCI NIH HHS/United States
    R01 CA062006/CA/NCI NIH HHS/United States
    R01 CA087014/CA/NCI NIH HHS/United States
    R01 CA092153/CA/NCI NIH HHS/United States
    R01 CA104682/CA/NCI NIH HHS/United States
    R01 CA154643/CA/NCI NIH HHS/United States
    R01 CA45614/CA/NCI NIH HHS/United States
    R01 CA87014/CA/NCI NIH HHS/United States
    R01 CA92153/CA/NCI NIH HHS/United States
    R01CA104682/CA/NCI NIH HHS/United States
    R03 CA089745/CA/NCI NIH HHS/United States
    R03CA89745/CA/NCI NIH HHS/United States
    U01 CA066529/CA/NCI NIH HHS/United States
    U01 CA66529/CA/NCI NIH HHS/United States
    U58 DP003862/DP/NCCDPHP CDC HHS/United States
  • Document Type:
  • Collection(s):
  • Description:
    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.

    Method

    Data on 4979 cases and 4752 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 leukaemia/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≥30kg m−2) was associated with DLBCL risk (OR=1.33, 95%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 two-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, P(interaction)=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.

    Impact

    Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma.