Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-control Study.
BACKGROUND
Kaposi sarcoma (KS) is a complication of KS-associated herpesvirus (KSHV) infection. Other oncogenic viral infections and malignancies are associated with certain HLA alleles and their natural killer (NK) cell immunoglobulin-like receptor (KIR) ligands. We tested whether HLA-KIR influences the risk of KSHV infection or KS.


METHODS
In population-based case-control studies, we compared HLA class I and KIR gene frequencies in 250 classic (non-AIDS) KS cases, 280 KSHV-seropositive controls, and 576 KSHV-seronegative controls composing discovery and validation cohorts. Logistic regression was used to calculate sex- and age-adjusted odds ratios (ORs) and 95% confidence intervals.


RESULTS
In both the discovery and validation cohorts, KS was associated with HLA-A*11:01 (adjusted OR for the combined cohorts, 0.4; P = .002) and HLA-C*07:01 (adjusted OR, 1.6; P = .002). Consistent associations across cohorts were also observed with activating KIR3DS1 plus HLA-B Bw4-80I and homozygosity for HLA-C group 1. With KIR3DS1 plus HLA-B Bw4-80I, the KSHV seroprevalence was 40% lower (adjusted OR for the combined cohorts, 0.6; P = .01), but the KS risk was 2-fold higher (adjusted OR, 2.1; P = .002). Similarly, the KSHV seroprevalence was 40% lower (adjusted OR, 0.6; P = .01) but the KS risk 80% higher with HLA-C group 1 homozygosity (adjusted OR, 1.8; P = .005).


CONCLUSIONS
KIR-mediated NK cell activation may decrease then risk of KSHV infection but enhance KSHV dissemination and progression to KS if infection occurs.
Division of Cancer Epidemiology and Genetics, Division of Cancer Epidemiology and Genetics, National Cancer Institute.
James J
JJ
Goedert
Cancer and Inflammation Program, Laboratory of Experimental Immunology Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
Maureen P
MP
Martin
Dipartimento di Igiene e Microbiologia Giuseppe D'Alessandro, Universitá degli Studi di Palermo.
Francesco
F
Vitale
Lega Italiana per la Lotta Contro i Tumori-Sez Ragusa, Italy.
Carmela
C
Lauria
Viral Oncology Section, AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Maryland.
Denise
D
Whitby
Cancer and Inflammation Program, Laboratory of Experimental Immunology Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
Ying
Y
Qi
Cancer and Inflammation Program, Laboratory of Experimental Immunology Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
Xiaojiang
X
Gao
Cancer and Inflammation Program, Laboratory of Experimental Immunology Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
Mary
M
Carrington
D016022:Case-Control Studies; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D019288:Herpesvirus 8, Human; D006801:Humans; D008213:Lymphocyte Activation; D054340:Receptors, KIR / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D012514:Sarcoma, Kaposi / Q000235:genetics*; D016036:Seroepidemiologic Studies
D006680:HLA Antigens; D054340:Receptors, KIR
Italy; Kaposi sarcoma; case-control study; human genetics; human leukocyte antigens; major histocompatibility complex; natural killer–cell immunoglobulin-like receptors