Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma.
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.
Cerhan
James R
JR
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. cerhan.james@mayo.edu
Ansell
Stephen M
SM
Fredericksen
Zachary S
ZS
Kay
Neil E
NE
Liebow
Mark
M
Call
Timothy G
TG
Dogan
Ahmet
A
Cunningham
Julie M
JM
Wang
Alice H
AH
Liu-Mares
Wen
W
Macon
William R
WR
Jelinek
Diane
D
Witzig
Thomas E
TE
Habermann
Thomas M
TM
Slager
Susan L
SL
D016022:Case-Control Studies; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007109:Immunity / Q000235:genetics*; D007249:Inflammation / Q000235:genetics*; D016015:Logistic Models; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk