title: Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma.
abstract: Studies have demonstrated that common polymorphisms in Th1 and Th2 cytokine genes can alter gene expression, modulate the balance between Th1/Th2 responsiveness, and influence susceptibility for autoimmune disorders, infectious diseases, and cancer. We analyzed one or more single nucleotide polymorphisms (SNPs) in 20 candidate Th1/Th2 genes in a population-based case-control study of non-Hodgkin lymphoma (NHL; n = 518 cases, 597 controls) among women in Connecticut. SNPs in critical genes, IL4, IL5, IL6, and IL10, were associated with risk for NHL and in some instances with a specific histologic subtype. Analysis of 4 SNPs in the IL10 promoter (-3575T>A, -1082A>G, -819C>T, and -592C>A) revealed that both the AGCC haplotype (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.21-1.96, P < .001) and the TATA haplotype (OR = 1.37, 95% CI = 1.05-1.79, P = .02) were associated with increased risk for B-cell lymphomas. In contrast, the IL4-1098G allele was associated with increased risk of T-cell lymphomas (OR = 3.84; 95% CI = 1.79-8.22; P < .001). Further, the IL10 and IL4 SNP associations remained significant after adjusting for multiple comparisons. These results suggest that SNPs in Th2 cytokine genes may be associated with risk of NHL.
authors.affiliation: Occupational & Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH/DHHS, MSC 7240, 6120 Executive Blvd, EPS 8109, Bethesda, MD 20892-7240, USA. qingl@mail.nih.gov
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Shelia H
authors.initials: SH
authors.lastname: Zahm
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holford
authors.forename: Brian
authors.initials: B
authors.lastname: Leaderer
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Robert
authors.initials: R
authors.lastname: Welch
authors.forename: Peter
authors.initials: P
authors.lastname: Boyle
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Zou
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002874:Chromosome Mapping; D016207:Cytokines / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020022:Genetic Predisposition to Disease; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044469:Racial Groups; D012189:Retrospective Studies; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D004273:DNA, Neoplasm