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Associations of Classic Kaposi Sarcoma with Common Variants in Genes that Modulate Host Immunity

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Rockville, Maryland; ² Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; ³ Core Genotyping Facility, Advanced Technology Center, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland; ⁴ Dipartimento di Igiene e Microbiologia Giuseppe D'Alessandro, Universitá degli studi di Palermo, Palermo, Italy; ⁵ Lega Italiana per la lotta contro i tumori-sez. Ragusa, Ragusa, Italy; ⁶ Servizio di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Istituti di Ricovero e Cura a Carattere Scientifico, Aviano, Italy; ⁷ Reparto di Epidemiologia, Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Rome, Italy; ⁸ Viral Epidemiology Section, AIDS Vaccine Program, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick, Frederick, Maryland; ⁹ Universitá di Catania, Catania, Italy; and ¹⁰ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland

Requests for reprints: Elizabeth E. Brown, National Cancer Institute, 6120 Executive Boulevard, EPS 8005/MSC 7248 Rockville, MD 20852. Phone: 301-496-8895; Fax: 301-402-0817. E-mail: brownbe{at}mail.nih.gov

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. (Cancer Epidemiol Biomarkers Prev 2006;15(5):926–34)