Polymorphism in cytokine genes as prognostic markers in Hodgkin's lymphoma.
BACKGROUND
In Hodgkin's lymphoma (HL), the production of cytokines by Reed-Sternberg cells and the surrounding tissue is thought to contribute to the biology of the disease. Cytokine expression can be altered by common single nucleotide polymorphisms (SNPs) in the 5'-promoter regions.


METHODS
We studied polymorphic allele variants of the cytokine genes interleukin (IL)-10 (T-3575A, G-2849A, C-2763A, A-1082G and C-592A), IL-6 (G-174C) and tumor necrosis factor-alpha (C-863A and G-308A) in 184 patients with HL, and analyzed for associations with treatment outcome.


RESULTS
Carriers of the IL-10-592AA and the IL-6-174GG genotypes had a significantly lower probability of freedom from treatment failure (FFTF) with adjusted hazard ratios (HRs) for failure of 2.92 [95% CI (confidence interval) 1.58-5.41, P = 0.001] and of 1.75 (95% CI 1.04-2.92, P = 0.03), respectively. Reconstructing haplotypes from the five SNPs in the IL-10 promoter revealed that homozygous carriers of the IL-10.4 haplotype (T-G-C-A-A) had a worse FFTF (HR, 2.35; 95% CI 1.2-4.6, P = 0.01). In the Cox multivariate analysis, the IL-10-592AA, the IL-6-174GG genotypes and stage were independent prognostic factors.


CONCLUSIONS
Our study indicates that cytokine genotypes predict clinical outcome in patients with HL and points to the importance of the genetic background of the host for treatment response.
Hohaus
S
S
Istituto di Ematologia e di Anatomia Patologica, Universita' Cattolica S. Cuore, Rome, Italy. stefan.hohaus@rm.unicatt.it
Giachelia
M
M
Di Febo
A
A
Martini
M
M
Massini
G
G
Vannata
B
B
D'Alo'
F
F
Guidi
F
F
Greco
M
M
Pierconti
F
F
Larocca
L M
LM
Voso
M T
MT
Leone
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014408:Biomarkers, Tumor; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10