Skibola, CF;Bracci, PM;Nieters, A;Brooks-Wilson, A;de Sanjose, S;Hughes, AM;Cerhan, JR;Skibola, DR;Purdue, M;Kane, E;Lan, Q;Foretova, L;Schenk, M;Spinelli, JJ;Slager, SL;De Roos, AJ;Smith, MT;Roman, E;Cozen, W;Boffetta, P;Kricker, A;Zheng, TZ;Lightfoot, T;Cocco, P;Benavente, Y;Zhang, YW;Hartge, P;Linet, MS;Becker, N;Brennan, P;Zhang, LP;Armstrong, B;Smith, A;Shiao, R;Novak, AJ;Maynadie, M;Chanock, SJ;Staines, A;Holford, TR;Holly, EA;Rothman, N;Wang, SS

2010

February

American Journal of Epidemiology

Tumor Necrosis Factor (TNF) and Lymphotoxin-alpha (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma in the InterLymph Consortium

Published

98 ()

SYSTEMIC-LUPUS-ERYTHEMATOSUS GENETIC-VARIATION POOLED ANALYSIS RHEUMATOID-ARTHRITIS FOLLICULAR LYMPHOMA SUN EXPOSURE SUSCEPTIBILITY PROMOTER IMMUNE INTERLEUKIN-10

171

267

276

In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G > A (rs1800629), lymphotoxin-alpha (LTA) 252A > G (rs909253), IL10 -3575T > A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF -308A carriers (NHL: per-allele odds ratio (OR(allelic)) = 1.10, P(trend) = 0.001; diffuse large B-cell lymphoma (DLBCL): OR(allelic) = 1.23, P(trend) = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: OR(allelic) = 1.13, P(trend) = 0.0001; DLBCL: OR(allelic) = 1.25, P(trend) = 3.7 x 10(-6); marginal zone lymphoma: OR(allelic) = 1.35, P(trend) = 0.004) and LTA 252G carriers (DLBCL: OR(allelic) = 1.12, P(trend) = 0.006; mycosis fungoides: OR(allelic) = 1.44, P(trend) = 0.015). The LTA 252A > G/TNF -308G > A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T > A and DLBCL (P(trend) = 0.02) and IL10 -1082A > G and mantle cell lymphoma (P(trend) = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A > G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.

CARY

0002-9262

10.1093/aje/kwp383