Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma

Sophia S. Wang, James R Cerhan, Patricia Hartge, Scott Davis, Wendy Cozen, Richard K. Severson, Nilanjan Chatterjee, Meredith Yeager, Stephen J. Chanock, Nathaniel Rothman

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Abstract

Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-α and lymphotoxin-α (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fcγ receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (Ptrend = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets.

Original languageEnglish (US)
Pages (from-to)9771-9780
Number of pages10
JournalCancer Research
Volume66
Issue number19
DOIs
StatePublished - Oct 1 2006

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Non-Hodgkin's Lymphoma
Single Nucleotide Polymorphism
Confidence Intervals
Genes
Odds Ratio
Haplotypes
Lymphotoxin-alpha
Population Control
Fc Receptors
B-Cell Chronic Lymphocytic Leukemia
Innate Immunity
Immunotherapy
Multicenter Studies
Lymphoma
B-Lymphocytes
Tumor Necrosis Factor-alpha
Genotype
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma. / Wang, Sophia S.; Cerhan, James R; Hartge, Patricia; Davis, Scott; Cozen, Wendy; Severson, Richard K.; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J.; Rothman, Nathaniel.

In: Cancer Research, Vol. 66, No. 19, 01.10.2006, p. 9771-9780.

Research output: Contribution to journalArticle

Wang, SS, Cerhan, JR, Hartge, P, Davis, S, Cozen, W, Severson, RK, Chatterjee, N, Yeager, M, Chanock, SJ & Rothman, N 2006, 'Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma', Cancer Research, vol. 66, no. 19, pp. 9771-9780. https://doi.org/10.1158/0008-5472.CAN-06-0324
Wang, Sophia S. ; Cerhan, James R ; Hartge, Patricia ; Davis, Scott ; Cozen, Wendy ; Severson, Richard K. ; Chatterjee, Nilanjan ; Yeager, Meredith ; Chanock, Stephen J. ; Rothman, Nathaniel. / Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma. In: Cancer Research. 2006 ; Vol. 66, No. 19. pp. 9771-9780.
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abstract = "Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95{\%} confidence intervals (95{\%} CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-α and lymphotoxin-α (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95{\%} CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95{\%} CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fcγ receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95{\%} CI, 1.01-1.56) and 1.41-fold (95{\%} CI, 1.10-1.81) increased risk, respectively (Ptrend = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets.",
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