Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma

Qing Lan, Tongzhang Zheng, Nathaniel Rothman, Yawei Zhang, Sophia S. Wang, Min Shen, Sonja I. Berndt, Shelia H. Zahm, Theodore R. Holford, Brian Leaderer, Meredith Yeager, Robert Welch, Peter Boyle, Bing Zhang, Kaiyong Zou, Yong Zhu, Stephen Chanock

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4101-4108
Number of pages8
JournalBlood
Volume107
Issue number10
DOIs
StatePublished - May 15 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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