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

Fabio Tramuto, Francesco Vitale, Georgina Mbisa, Amy Hutchinson, Barbara Kroner, Renee Chen, Concetta Castilletti, Jinbo Chen, Lorenzo Gafa, James J. Goedert, Elizabeth E. Brown, Francesca Farchi, Ingo Ruczinski, Catia Valdarchi, Carmela Lauria, Pierluca Piselli, Anna Crispo, Paolo Ascierto, Brian Staats, Nilanjan ChatterjeeMichele Massimino, Maureen Kiley, Maria Rosaria De Marco, Rosa Maria Corona, Mario Tamburini, Stephen J. Chanock, Stefania Stella, Diego Serraino, Denise Whitby, Mauizio Montella, Aldo Di Carlo, Angelo Messina, Giovanni Rezza, Daniele Fallin, Sonia De Sicato

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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.
Lingua originaleEnglish
pagine (da-a)926-934
Numero di pagine9
RivistaCANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume15(5)
Stato di pubblicazionePublished - 2006

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All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

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Tramuto, F., Vitale, F., Mbisa, G., Hutchinson, A., Kroner, B., Chen, R., Castilletti, C., Chen, J., Gafa, L., Goedert, J. J., Brown, E. E., Farchi, F., Ruczinski, I., Valdarchi, C., Lauria, C., Piselli, P., Crispo, A., Ascierto, P., Staats, B., ... De Sicato, S. (2006). Associations of Classic Kaposi Sarcoma with Common Variants in Genes that Modulate Host Immunity. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 15(5), 926-934.