Associations of classic Kaposi sarcoma with common variants in genes that modulate host immunity.
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.
Brown
Elizabeth E
EE
National Cancer Institute, 6120 Executive Boulevard, EPS 8005/MSC 7248 Rockville, MD 20852, USA. brownbe@mail.nih.gov
Fallin
Daniele
D
Ruczinski
Ingo
I
Hutchinson
Amy
A
Staats
Brian
B
Vitale
Francesco
F
Lauria
Carmela
C
Serraino
Diego
D
Rezza
Giovanni
G
Mbisa
Georgina
G
Whitby
Denise
D
Messina
Angelo
A
Goedert
James J
JJ
Chanock
Stephen J
SJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D019288:Herpesvirus 8, Human / Q000235:genetics; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012514:Sarcoma, Kaposi / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology
D016207:Cytokines