Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma

James R Cerhan, Stephen Maxted Ansell, Zachary S. Fredericksen, Neil Elliot Kay, Mark Liebow, Timothy G. Call, Ahmet Dogan, Julie M Cunningham, Alice H. Wang, Wen Liu-Mares, William R. Macon, Diane F Jelinek, Thomas Elmer Witzig, Thomas Matthew Habermann, Susan L Slager

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Abstract

Smaller-scale evaluations suggest that common genetic variation in candidate genes related to immune function may predispose to the development of non-Hodgkin lymphoma (NHL). We report an analysis of variants within genes associated with immunity and inflammation and risk of NHL using a panel of 9412 single-nucleotide polymorphisms (SNPs) from 1253 genes in a study of 458 patients with NHL and 484 frequency-matched controls. We modeled haplotypes and risk of NHL, as well as the main effects for all independent SNPs from a gene in multivariate logistic regression models; we separately report results for nonsynonymous (ns) SNPs. In gene-level analyses, the strongest findings (P ≤ .001) were for CREB1, FGG, MAP3K5, RIPK3, LSP1, TRAF1, DUSP2, and ITGB3. In nsSNP analyses, the strongest findings (P ≤ .01) were for ITGB3 L59P (odds ratio [OR] = 0.66; 95% confidence interval [CI] 0.52-0.85), TLR6 V427A (OR = 5.20; CI 1.77-15.3), SELPLG M264V (OR = 3.20; CI 1.48-6.91), UNC84B G671S (OR = 1.50; CI 1.12-2.00), B3GNT3 H328R (OR = 0.74; CI 0.59-0.93), and BAT2 V1883L (OR = 0.64; CI 0.45-0.90). Our results suggest that genetic variation in genes associated with immune response (TRAF1, RIPK3, BAT2, and TLR6), mitogen-activated protein kinase (MAPK) signaling (MAP3K5, DUSP2, and CREB1), lymphocyte trafficking and migration (B3GNT3, SELPLG, and LSP1), and coagulation pathways (FGG and ITGB3) may be important in the etiology of NHL, and should be prioritized in replication studies.

Original languageEnglish (US)
Pages (from-to)4455-4463
Number of pages9
JournalBlood
Volume110
Issue number13
DOIs
StatePublished - Dec 15 2007

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Non-Hodgkin's Lymphoma
Genes
Odds Ratio
Confidence Intervals
Inflammation
TNF Receptor-Associated Factor 1
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Logistic Models
Lymphocytes
Mitogen-Activated Protein Kinases
Coagulation
Haplotypes
Logistics
Immunity

ASJC Scopus subject areas

  • Hematology

Cite this

Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma. / Cerhan, James R; Ansell, Stephen Maxted; Fredericksen, Zachary S.; Kay, Neil Elliot; Liebow, Mark; Call, Timothy G.; Dogan, Ahmet; Cunningham, Julie M; Wang, Alice H.; Liu-Mares, Wen; Macon, William R.; Jelinek, Diane F; Witzig, Thomas Elmer; Habermann, Thomas Matthew; Slager, Susan L.

In: Blood, Vol. 110, No. 13, 15.12.2007, p. 4455-4463.

Research output: Contribution to journalArticle

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abstract = "Smaller-scale evaluations suggest that common genetic variation in candidate genes related to immune function may predispose to the development of non-Hodgkin lymphoma (NHL). We report an analysis of variants within genes associated with immunity and inflammation and risk of NHL using a panel of 9412 single-nucleotide polymorphisms (SNPs) from 1253 genes in a study of 458 patients with NHL and 484 frequency-matched controls. We modeled haplotypes and risk of NHL, as well as the main effects for all independent SNPs from a gene in multivariate logistic regression models; we separately report results for nonsynonymous (ns) SNPs. In gene-level analyses, the strongest findings (P ≤ .001) were for CREB1, FGG, MAP3K5, RIPK3, LSP1, TRAF1, DUSP2, and ITGB3. In nsSNP analyses, the strongest findings (P ≤ .01) were for ITGB3 L59P (odds ratio [OR] = 0.66; 95{\%} confidence interval [CI] 0.52-0.85), TLR6 V427A (OR = 5.20; CI 1.77-15.3), SELPLG M264V (OR = 3.20; CI 1.48-6.91), UNC84B G671S (OR = 1.50; CI 1.12-2.00), B3GNT3 H328R (OR = 0.74; CI 0.59-0.93), and BAT2 V1883L (OR = 0.64; CI 0.45-0.90). Our results suggest that genetic variation in genes associated with immune response (TRAF1, RIPK3, BAT2, and TLR6), mitogen-activated protein kinase (MAPK) signaling (MAP3K5, DUSP2, and CREB1), lymphocyte trafficking and migration (B3GNT3, SELPLG, and LSP1), and coagulation pathways (FGG and ITGB3) may be important in the etiology of NHL, and should be prioritized in replication studies.",
author = "Cerhan, {James R} and Ansell, {Stephen Maxted} and Fredericksen, {Zachary S.} and Kay, {Neil Elliot} and Mark Liebow and Call, {Timothy G.} and Ahmet Dogan and Cunningham, {Julie M} and Wang, {Alice H.} and Wen Liu-Mares and Macon, {William R.} and Jelinek, {Diane F} and Witzig, {Thomas Elmer} and Habermann, {Thomas Matthew} and Slager, {Susan L}",
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AU - Cerhan, James R

AU - Ansell, Stephen Maxted

AU - Fredericksen, Zachary S.

AU - Kay, Neil Elliot

AU - Liebow, Mark

AU - Call, Timothy G.

AU - Dogan, Ahmet

AU - Cunningham, Julie M

AU - Wang, Alice H.

AU - Liu-Mares, Wen

AU - Macon, William R.

AU - Jelinek, Diane F

AU - Witzig, Thomas Elmer

AU - Habermann, Thomas Matthew

AU - Slager, Susan L

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N2 - Smaller-scale evaluations suggest that common genetic variation in candidate genes related to immune function may predispose to the development of non-Hodgkin lymphoma (NHL). We report an analysis of variants within genes associated with immunity and inflammation and risk of NHL using a panel of 9412 single-nucleotide polymorphisms (SNPs) from 1253 genes in a study of 458 patients with NHL and 484 frequency-matched controls. We modeled haplotypes and risk of NHL, as well as the main effects for all independent SNPs from a gene in multivariate logistic regression models; we separately report results for nonsynonymous (ns) SNPs. In gene-level analyses, the strongest findings (P ≤ .001) were for CREB1, FGG, MAP3K5, RIPK3, LSP1, TRAF1, DUSP2, and ITGB3. In nsSNP analyses, the strongest findings (P ≤ .01) were for ITGB3 L59P (odds ratio [OR] = 0.66; 95% confidence interval [CI] 0.52-0.85), TLR6 V427A (OR = 5.20; CI 1.77-15.3), SELPLG M264V (OR = 3.20; CI 1.48-6.91), UNC84B G671S (OR = 1.50; CI 1.12-2.00), B3GNT3 H328R (OR = 0.74; CI 0.59-0.93), and BAT2 V1883L (OR = 0.64; CI 0.45-0.90). Our results suggest that genetic variation in genes associated with immune response (TRAF1, RIPK3, BAT2, and TLR6), mitogen-activated protein kinase (MAPK) signaling (MAP3K5, DUSP2, and CREB1), lymphocyte trafficking and migration (B3GNT3, SELPLG, and LSP1), and coagulation pathways (FGG and ITGB3) may be important in the etiology of NHL, and should be prioritized in replication studies.

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