Tumor necrosis factor (TNF) and lymphotoxin-α (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium

Christine F. Skibola, Paige M. Bracci, Alexandra Nieters, Angela Brooks-Wilson, Silvia De Sanjosé, Ann Maree Hughes, James R Cerhan, Danica R. Skibola, Mark Purdue, Eleanor Kane, Qing Lan, Lenka Foretova, Maryjean Schenk, John J. Spinelli, Susan L Slager, Anneclaire J. De Roos, Martyn T. Smith, Eve Roman, Wendy Cozen, Paolo BoffettaAnne Kricker, Tongzhang Zheng, Tracy Lightfoot, Pierluigi Cocco, Yolanda Benavente, Yawei Zhang, Patricia Hartge, Martha S. Linet, Nikolaus Becker, Paul Brennan, Luoping Zhang, Bruce Armstrong, Alex Smith, Renee Shiao, Anne J Novak, Marc Maynadie, Stephen J. Chanock, Anthony Staines, Theodore R. Holford, Elizabeth A. Holly, Nathaniel Rothman, Sophia S. Wang

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Abstract

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-α (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 (ORallelic)=1.10, Ptrend=0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic=1.23, Ptrend=0.004). In the combined population, odds ratios were increased for TNF-308A carriers (NHL: ORallelic=1.13, Ptrend=0.0001; DLBCL: ORallelic=1.25, Ptrend=3.7 × 10-6; marginal zone lymphoma: ORallelic=1.35, Ptrend=0.004) and LTA 252G carriers (DLBCL: ORallelic=1.12, Ptrend = 0.006; mycosis fungoides: ORallelic=1.44, Ptrend=0.015). The LTA 252A>G/TNF-308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P=2.9 × 10 -8). Results suggested associations between IL10-3575T>A and DLBCL (Ptrend=0.02) and IL10-1082A>G and mantle cell lymphoma (Ptrend=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.

Original languageEnglish (US)
Pages (from-to)267-276
Number of pages10
JournalAmerican Journal of Epidemiology
Volume171
Issue number3
DOIs
StatePublished - Feb 2010

Fingerprint

Lymphotoxin-alpha
Non-Hodgkin's Lymphoma
Lymphoma, Large B-Cell, Diffuse
Tumor Necrosis Factor-alpha
Interleukin-10
Odds Ratio
Lymphoma
Alleles
Genes
Mantle-Cell Lymphoma
Mycosis Fungoides
Gastrin-Secreting Cells
Linkage Disequilibrium
Haplotypes
Case-Control Studies
Immune System
Epidemiology
Nucleotides

Keywords

  • Lymphoma
  • Lymphoma, non-Hodgkin
  • Lymphotoxin-alpha
  • Meta-analysis
  • Polymorphism, genetic
  • Polymorphism, single nucleotide
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Epidemiology

Cite this

Skibola, C. F., Bracci, P. M., Nieters, A., Brooks-Wilson, A., De Sanjosé, S., Hughes, A. M., ... Wang, S. S. (2010). Tumor necrosis factor (TNF) and lymphotoxin-α (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium. American Journal of Epidemiology, 171(3), 267-276. https://doi.org/10.1093/aje/kwp383

Tumor necrosis factor (TNF) and lymphotoxin-α (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium. / Skibola, Christine F.; Bracci, Paige M.; Nieters, Alexandra; Brooks-Wilson, Angela; De Sanjosé, Silvia; Hughes, Ann Maree; Cerhan, James R; Skibola, Danica R.; Purdue, Mark; Kane, Eleanor; Lan, Qing; Foretova, Lenka; Schenk, Maryjean; Spinelli, John J.; Slager, Susan L; De Roos, Anneclaire J.; Smith, Martyn T.; Roman, Eve; Cozen, Wendy; Boffetta, Paolo; Kricker, Anne; Zheng, Tongzhang; Lightfoot, Tracy; Cocco, Pierluigi; Benavente, Yolanda; Zhang, Yawei; Hartge, Patricia; Linet, Martha S.; Becker, Nikolaus; Brennan, Paul; Zhang, Luoping; Armstrong, Bruce; Smith, Alex; Shiao, Renee; Novak, Anne J; Maynadie, Marc; Chanock, Stephen J.; Staines, Anthony; Holford, Theodore R.; Holly, Elizabeth A.; Rothman, Nathaniel; Wang, Sophia S.

In: American Journal of Epidemiology, Vol. 171, No. 3, 02.2010, p. 267-276.

Research output: Contribution to journalArticle

Skibola, CF, Bracci, PM, Nieters, A, Brooks-Wilson, A, De Sanjosé, 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, T, Lightfoot, T, Cocco, P, Benavente, Y, Zhang, Y, Hartge, P, Linet, MS, Becker, N, Brennan, P, Zhang, L, Armstrong, B, Smith, A, Shiao, R, Novak, AJ, Maynadie, M, Chanock, SJ, Staines, A, Holford, TR, Holly, EA, Rothman, N & Wang, SS 2010, 'Tumor necrosis factor (TNF) and lymphotoxin-α (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium', American Journal of Epidemiology, vol. 171, no. 3, pp. 267-276. https://doi.org/10.1093/aje/kwp383
Skibola, Christine F. ; Bracci, Paige M. ; Nieters, Alexandra ; Brooks-Wilson, Angela ; De Sanjosé, Silvia ; Hughes, Ann Maree ; Cerhan, James R ; Skibola, Danica R. ; Purdue, Mark ; Kane, Eleanor ; Lan, Qing ; Foretova, Lenka ; Schenk, Maryjean ; Spinelli, John J. ; Slager, Susan L ; De Roos, Anneclaire J. ; Smith, Martyn T. ; Roman, Eve ; Cozen, Wendy ; Boffetta, Paolo ; Kricker, Anne ; Zheng, Tongzhang ; Lightfoot, Tracy ; Cocco, Pierluigi ; Benavente, Yolanda ; Zhang, Yawei ; Hartge, Patricia ; Linet, Martha S. ; Becker, Nikolaus ; Brennan, Paul ; Zhang, Luoping ; Armstrong, Bruce ; Smith, Alex ; Shiao, Renee ; Novak, Anne J ; Maynadie, Marc ; Chanock, Stephen J. ; Staines, Anthony ; Holford, Theodore R. ; Holly, Elizabeth A. ; Rothman, Nathaniel ; Wang, Sophia S. / Tumor necrosis factor (TNF) and lymphotoxin-α (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium. In: American Journal of Epidemiology. 2010 ; Vol. 171, No. 3. pp. 267-276.
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TY - JOUR

T1 - Tumor necrosis factor (TNF) and lymphotoxin-α (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium

AU - Skibola, Christine F.

AU - Bracci, Paige M.

AU - Nieters, Alexandra

AU - Brooks-Wilson, Angela

AU - De Sanjosé, Silvia

AU - Hughes, Ann Maree

AU - Cerhan, James R

AU - Skibola, Danica R.

AU - Purdue, Mark

AU - Kane, Eleanor

AU - Lan, Qing

AU - Foretova, Lenka

AU - Schenk, Maryjean

AU - Spinelli, John J.

AU - Slager, Susan L

AU - De Roos, Anneclaire J.

AU - Smith, Martyn T.

AU - Roman, Eve

AU - Cozen, Wendy

AU - Boffetta, Paolo

AU - Kricker, Anne

AU - Zheng, Tongzhang

AU - Lightfoot, Tracy

AU - Cocco, Pierluigi

AU - Benavente, Yolanda

AU - Zhang, Yawei

AU - Hartge, Patricia

AU - Linet, Martha S.

AU - Becker, Nikolaus

AU - Brennan, Paul

AU - Zhang, Luoping

AU - Armstrong, Bruce

AU - Smith, Alex

AU - Shiao, Renee

AU - Novak, Anne J

AU - Maynadie, Marc

AU - Chanock, Stephen J.

AU - Staines, Anthony

AU - Holford, Theodore R.

AU - Holly, Elizabeth A.

AU - Rothman, Nathaniel

AU - Wang, Sophia S.

PY - 2010/2

Y1 - 2010/2

N2 - 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-α (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 (ORallelic)=1.10, Ptrend=0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic=1.23, Ptrend=0.004). In the combined population, odds ratios were increased for TNF-308A carriers (NHL: ORallelic=1.13, Ptrend=0.0001; DLBCL: ORallelic=1.25, Ptrend=3.7 × 10-6; marginal zone lymphoma: ORallelic=1.35, Ptrend=0.004) and LTA 252G carriers (DLBCL: ORallelic=1.12, Ptrend = 0.006; mycosis fungoides: ORallelic=1.44, Ptrend=0.015). The LTA 252A>G/TNF-308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P=2.9 × 10 -8). Results suggested associations between IL10-3575T>A and DLBCL (Ptrend=0.02) and IL10-1082A>G and mantle cell lymphoma (Ptrend=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.

AB - 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-α (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 (ORallelic)=1.10, Ptrend=0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic=1.23, Ptrend=0.004). In the combined population, odds ratios were increased for TNF-308A carriers (NHL: ORallelic=1.13, Ptrend=0.0001; DLBCL: ORallelic=1.25, Ptrend=3.7 × 10-6; marginal zone lymphoma: ORallelic=1.35, Ptrend=0.004) and LTA 252G carriers (DLBCL: ORallelic=1.12, Ptrend = 0.006; mycosis fungoides: ORallelic=1.44, Ptrend=0.015). The LTA 252A>G/TNF-308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P=2.9 × 10 -8). Results suggested associations between IL10-3575T>A and DLBCL (Ptrend=0.02) and IL10-1082A>G and mantle cell lymphoma (Ptrend=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.

KW - Lymphoma

KW - Lymphoma, non-Hodgkin

KW - Lymphotoxin-alpha

KW - Meta-analysis

KW - Polymorphism, genetic

KW - Polymorphism, single nucleotide

KW - Tumor necrosis factor-alpha

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