Hodgkin disease risk: Role of genetic polymorphisms and gene–gene interactions in inflammation pathway genes

✍ Scribed by Claudia M. Monroy; Andrea C. Cortes; Mirtha S. Lopez; Anthony M. D'Amelio Jr.; Carol J. Etzel; Anas Younes; Sara S. Strom; Randa A. El-Zein

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 127 KB
• Volume: 50
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20688

✦ Synopsis

Abstract

Inflammation is a critical component of cancer development. The clinical and pathological features of Hodgkin disease (HD) reflect an abnormal immunity that results from cytokines secreted by Reed–Sternberg cells and the surrounding tumor. Numerous studies have reported the association between genetic polymorphisms in cytokine genes and the susceptibility to different hematologic cancers. However, the effects of such SNPs on modulating HD risk have not yet been investigated. We hypothesized that gene–gene interactions between candidate genes in the anti‐ and pro‐inflammatory pathways carrying suspicious polymorphisms may contribute to susceptibility to HD. To test this hypothesis, we conducted a study on 200 HD cases and 220 controls to assess associations between HD risk and 38 functional SNPs in inflammatory genes. We evaluated potential gene–gene interactions using a multi‐analytic strategy combining logistic regression, multi‐factor dimensionality reduction, and classification and regression tree (CART) approaches. We observed that, in combination, allelic variants in the COX2, IL18, ILR4, and IL10 genes modify the risk for developing HD. Moreover, the cumulative genetic risk score (CGRS) revealed a significant trend where the risk for developing HD increases as the number of adverse alleles in the cytokine genes increase. These findings support the notion that epigenetic‐interactions between these cytokines may influence pathogenesis of HD modulating the proliferation of regulatory T cells. In this way, the innate and adaptative immune responses may be altered and defy their usual functions in the host anti‐tumor response. Our study is the first to report the association between polymorphisms in inflammation genes and HD susceptibility risk. Mol. Carcinog. © 2010 Wiley‐Liss, Inc.