Associations of classic Kaposi sarcoma with common variants in genes that modulate host immunity

Elizabeth E. Brown, Daniele Fallin, Ingo Ruczinski, Amy Hutchinson, Brian Staats, Francesco Vitale, Carmela Lauria, Diego Serraino, Giovanni Rezza, Georgina Mbisa, Denise Whitby, Angelo Messina, James J. Goedert, Stephen J. Chanock

Research output: Contribution to journalArticle

Abstract

Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm primarily caused by Kaposi sarcoma-associated herpesvirus (KSHV). Kaposi sarcoma lesions are characterized, in part, by the presence of proinflammatory cytokines and growth factors thought to regulate KSHV replication and CKS pathogenesis. Using genomic DNA extracted from 133 CKS cases and 172 KSHV-latent nuclear antigen-positive, population-based controls in Italy without HIV infection, we examined the risk of CKS associated with 28 common genetic variants in 14 immune-modulating genes. Haplotypes were estimated for IL1A, IL1B, IL4, IL8, IL8RB, IL10, IL12A, IL13, and TNF. Compared with controls, CKS risk was decreased with 1235T/-1010G-containing diplotypes of IL8RB (odds ratio, 0.49; 95% confidence interval, 0.30-0.78; P = 0.003), whereas risk was increased with diplotypes of IL13 containing the promoter region variant 98A (rs20541, alias +130; odds ratio, 1.88; 95% confidence interval, 1.15-3.08; P = 0.01) when considered in multivariate analysis. Risk estimates did not substantially vary by age, sex, incident disease, or disease burden. Our data provide preliminary evidence for variants in immune-modulating genes that could influence the risk of CKS. Among KSHV-seropositive Italians, CKS risk was associated with diplotypes of IL8RB and IL13, supporting laboratory evidence of immune-mediated pathogenesis.

Original languageEnglish
Pages (from-to)926-934
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume15
Issue number5
DOIs
Publication statusPublished - May 2006

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Brown, E. E., Fallin, D., Ruczinski, I., Hutchinson, A., Staats, B., Vitale, F., Lauria, C., Serraino, D., Rezza, G., Mbisa, G., Whitby, D., Messina, A., Goedert, J. J., & Chanock, S. J. (2006). Associations of classic Kaposi sarcoma with common variants in genes that modulate host immunity. Cancer Epidemiology Biomarkers and Prevention, 15(5), 926-934. https://doi.org/10.1158/1055-9965.EPI-05-0791