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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium.

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.[1]

References

  1. Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium. Skibola, C.F., Bracci, P.M., Nieters, A., Brooks-Wilson, A., de Sanjosé, S., Hughes, A.M., Cerhan, J.R., Skibola, D.R., Purdue, M., Kane, E., Lan, Q., Foretova, L., Schenk, M., Spinelli, J.J., Slager, S.L., De Roos, A.J., Smith, M.T., Roman, E., Cozen, W., Boffetta, P., Kricker, A., Zheng, T., Lightfoot, T., Cocco, P., Benavente, Y., Zhang, Y., Hartge, P., Linet, M.S., Becker, N., Brennan, P., Zhang, L., Armstrong, B., Smith, A., Shiao, R., Novak, A.J., Maynadie, M., Chanock, S.J., Staines, A., Holford, T.R., Holly, E.A., Rothman, N., Wang, S.S. Am. J. Epidemiol. (2010) [Pubmed]
 
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