Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: a pooled analysis of three population-based case-control studies
| Autor: | Qing, Lan, Sophia S, Wang, Idan, Menashe, Bruce, Armstrong, Yawei, Zhang, Patricia, Hartge, Mark P, Purdue, Theodore R, Holford, Lindsay M, Morton, Anne, Kricker, James R, Cerhan, Andrew, Grulich, Wendy, Cozen, Shelia H, Zahm, Meredith, Yeager, Claire M, Vajdic, Maryjean, Schenk, Brian, Leaderer, Jeff, Yuenger, Richard K, Severson, Nilanjan, Chatterjee, Stephen J, Chanock, Tongzhang, Zheng, Nathaniel, Rothman |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Genotype Lymphoma Non-Hodgkin Genetic Variation Middle Aged Th1 Cells Polymorphism Single Nucleotide Article Cell Transformation Neoplastic Th2 Cells immune system diseases hemic and lymphatic diseases Case-Control Studies Cytokines Humans Female Genetic Predisposition to Disease Aged Genes Neoplasm Signal Transduction |
| Zdroj: | British journal of haematology. 153(3) |
| ISSN: | 1365-2141 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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