title: Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: a pooled analysis of three population-based case-control studies.
abstract: The balance between T-helper 1 (Th1) and T-helper 2 (Th2) activity is critical in lymphoid cell development and differentiation. Immune dysfunction underlies lymphomagenesis, so an alteration in the regulation of key Th1/Th2 cytokines may lead to the development of non-Hodgkin lymphoma (NHL). To study the impact of polymorphisms in Th1/Th2 cytokines on NHL risk, we analyzed 145 tag single nucleotide polymorphisms (SNPs) in 17 Th1/Th2 cytokine and related genes in three population-based case-control studies (1946 cases and 1808 controls). Logistic regression was used to compute odds ratios (OR) for NHL and four major NHL subtypes in relation to tag SNP genotypes and haplotypes. A gene-based analysis adjusting for the number of tag SNPs genotyped in each gene showed significant associations with risk of NHL combined and one or more NHL subtypes for Th1 (IL12A and IL12RB1) and Th2 (IL4, IL10RB, and IL18) genes. The strongest association was for rs485497 in IL12A, which plays a central role in bridging the cellular and humoral pathways of innate resistance and antigen-specific adaptive immune responses (allele risk OR= 1·17; P(trend)= 0·00099). This SNP was also associated specifically with risk of follicular lymphoma (allele risk OR= 1·26; P(trend)= 0·0012). These findings suggest that genetic variation in Th1/Th2 cytokine genes may contribute to lymphomagenesis.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, MD, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Idan
authors.initials: I
authors.lastname: Menashe
authors.forename: Bruce
authors.initials: B
authors.lastname: Armstrong
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holford
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morton
authors.forename: Anne
authors.initials: A
authors.lastname: Kricker
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Andrew
authors.initials: A
authors.lastname: Grulich
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Shelia H
authors.initials: SH
authors.lastname: Zahm
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Claire M
authors.initials: CM
authors.lastname: Vajdic
authors.forename: Maryjean
authors.initials: M
authors.lastname: Schenk
authors.forename: Brian
authors.initials: B
authors.lastname: Leaderer
authors.forename: Jeff
authors.initials: J
authors.lastname: Yuenger
authors.forename: Richard K
authors.initials: RK
authors.lastname: Severson
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D005260:Female; D052138:Genes, Neoplasm / Q000276:immunology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines