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Blood, 1 October 2000, Vol. 96, No. 7, pp. 2562-2567
NEOPLASIA
An IL6 promoter polymorphism is associated with a
lifetime risk of development of Kaposi sarcoma in men infected with
human immunodeficiency virus
Charles B. Foster,
Thomas Lehrnbecher,
Susan Samuels,
Steven Stein,
Femke Mol,
Julie A. Metcalf,
Kathleen Wyvill,
Seth M. Steinberg,
Joseph Kovacs,
Andrew Blauvelt,
Robert Yarchoan, and
Stephen J. Chanock
From the Immunocompromised Host Section, Pediatric
Oncology Branch, National Cancer Institute (NCI), National Institutes
of Health (NIH); Laboratory of Immunoregulation, National Institute of
Allergy and Infectious Diseases, NIH; HIV and AIDS Malignancy Branch,
NCI, NIH; Biostatistics and Data Management, NCI, NIH; Critical Care
Medicine Department, Clinical Center, NIH; and the Dermatology Branch,
NCI, NIH, Bethesda, MD.
Kaposi sarcoma (KS) is an angioproliferative inflammatory condition
that occurs commonly in patients infected with human immunodeficiency virus (HIV). Inflammatory cytokines and growth factors promote the
development of KS. Because physiologically important cytokine polymorphisms modulate host inflammatory responses, we investigated the
association between KS and common regulatory polymorphisms in 5 proinflammatory cytokine genes encoding interleukin (IL) IL-1 ,
IL-1 , tumor necrosis factor (TNF) , TNF-, and IL-6 and in the
IL-1 receptor antagonist (IL1RN). We also examined the contribution of stromal-derived factor 1 and chemokine receptor 5 ( 32) polymorphisms to KS development. The population consisted of
115 HIV-infected men with KS and 126 deceased HIV-infected men without
KS. The only strong association was observed between an IL6
promoter polymorphism (G-174C) and susceptibility to KS in HIV-infected
men (P = .0035). Homozygotes for IL6 allele
G, associated with increased IL6 production, were
overrepresented among patients with KS (P = .0046),
whereas allele C homozygotes were underrepresented
(P = .0062). Substantial in vitro evidence indicates that
IL-6 contributes to the pathogenesis of KS. Our results show that
IL6 promoter genotypes associated with altered gene
expression are risk factors for development of KS. Identification of a
genetic risk factor for development of KS has important clinical implications for prevention and therapy.
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