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Abstract

Title: Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma.
Author: Lan Q, Zheng T, Rothman N, Zhang Y, Wang SS, Shen M, Berndt SI, Zahm SH, Holford TR, Leaderer B, Yeager M, Welch R, Boyle P, Zhang B, Zou K, Zhu Y, Chanock S
Journal: Blood 107:4101-4108
Year: 2006
Month: January

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 auto-immune 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 four SNPs in the IL10 promoter (-3575T >A, -1082A >G, -819C >T, and -592C >A) revealed that both the AGCC haplotype (OR = 1.54, 95% CI = 1.21-1.96, P < 0.001) and the TATA haplotype (OR = 1.37, 95% CI = 1.05-1.79, P = 0.02) 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 < 0.001). 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.