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PMID: 17827388 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Blood ·Vol. 110 ·No. 13 ·2007-12-15 ·Pages 4455-63

Cerhan JR, Ansell SM, Fredericksen ZS, Kay NE, Liebow M, Call TG, Dogan A, Cunningham JM, Wang AH, Liu-Mares W, Macon WR, Jelinek D, Witzig TE, Habermann TM, Slager SL

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 < or = .001) were for CREB1, FGG, MAP3K5, RIPK3, LSP1, TRAF1, DUSP2, and ITGB3. In nsSNP analyses, the strongest findings (P < or = .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.

MeSH Terms
Case-Control Studies Genes, Neoplasm Genetic Predisposition to Disease/epidemiology,genetics Genetic Variation/genetics Haplotypes Humans Immunity/genetics Inflammation/genetics Logistic Models Lymphoma, Non-Hodgkin/epidemiology,etiology,genetics Polymorphism, Single Nucleotide Risk
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Cerhan James R
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. [email protected]
Ansell Stephen M
Fredericksen Zachary S
Kay Neil E
Liebow Mark
Call Timothy G
Dogan Ahmet
Cunningham Julie M
Wang Alice H
Liu-Mares Wen
Macon William R
Jelinek Diane
Witzig Thomas E
Habermann Thomas M
Slager Susan L
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2007-05-088682
Email
[email protected]
Published
2007-12-15
Epub
2007-00-07
Pages
4455-63
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2234796
Subset
IM
Grants
NCI NIH HHS · R25 CA092049 · United States
NCI NIH HHS · K07 CA94919 · United States
NCI NIH HHS · R01 CA092153 · United States
NCI NIH HHS · R01 CA92153 · United States
NCI NIH HHS · K07 CA094919 · United States
External Links
PubMed source DOI: 10.1182/blood-2007-05-088682 PMC Full Text View journal details
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