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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4101-4108.
Prepublished online as a Blood First Edition Paper on January 31, 2006; DOI 10.1182/blood-2005-10-4160.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
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, and
Stephen Chanock
From the Division of Cancer Epidemiology and Genetics, and the Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, MD; the Department of Epidemiology and Public Health, Yale School of Medicine, and the Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT; the International Agency for Research on Cancer, Lyon, France; and the Department of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada.
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.
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