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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4455-4463.
Prepublished online as a Blood First Edition Paper on September 7, 2007; DOI 10.1182/blood-2007-05-088682.


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Submitted May 3, 2007
Accepted September 2, 2007

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

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

Division of Epidemiology, Dept of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, United States
Division of Biostatistics, Dept of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, United States
Division of Hematology, Dept of Medicine, Mayo Clinic College of Medicine, Rochester, MN, United States
Division of General Internal Medicine, Dept of Medicine, Mayo Clinic College of Medicine, Rochester, MN, United States
Division of Hematopathology, Dept of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, United States
Division of Experimental Pathogy, Dept of Laboratory medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, United States
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, United States

* Corresponding author; email: cerhan.james{at}mayo.edu.

Smaller scale evaluations suggest that common genetic variation in candidate genes related to immune function may predispose to the development of NHL. We report an analysis of variants within genes associated with immunity and inflammation and risk of NHL using a panel of 9,412 single nucleotide polymorphisms (SNPs) from 1,253 genes in a study of 458 NHL cases 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 non-synonymous (ns) SNPs. In gene-level analyses, the strongest findings (p≤0.001) were for CREB1, FGG, MAP3K5, RIPK3, LSP1, TRAF1, DUSP2, and ITGB3. In nsSNP analyses, the strongest findings (p≤0.01) were for ITGB3 L59P (OR=0.66, 0.52-0.85), TLR6 V427A (OR=5.20, 1.77-15.3), SELPLG M264V (OR=3.20, 1.48-6.91), UNC84B G671S (OR=1.50, 1.12-2.00), B3GNT3 H328R (OR=0.74, 0.59-0.93), and BAT2 V1883L (OR=0.64, 0.45-0.90). Our results suggest that genetic variation in genes associated with immune response (TRAF1, RIPK3, BAT2, TLR6), MAPK signaling (MAP3K5, DUSP2 and CREB1), lymphocyte trafficking and migration (B3GNT3, SELPLG, LSP1), and coagulation pathways (FGG, ITGB3) may be important in the etiology of NHL, and should be prioritized in replication studies.


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