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Impact of interleukin-10 polymorphisms (–1082 and –3575) on the survival of patients with lymphoid neoplasms

From the Department of Hematology, Institut Catalá d’Oncología, L’Hospitalet de Llobregat, Spain (ED-D, EG-B, AFdS); Department of Epidemiology, Institut Catalá d’Oncología, L’Hospitalet de Llobregat, Spain (YB, SdS); Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain (CM); Department of Oncology, Hospital Universitari San Joan, Reus, URV, Spain (JG); Department of Pathology, Hospital Verge de la Cinta, Tortosa, Spain (RB); Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA (SSW, Ql, NR)

Correspondence: Eva Domingo Domènech, Department of Hematology, Institut Català d’Oncologia, Avda. Gran Via s/n, km 2.7, 08907 L’Hospitalet de Llobregat, Barcelona, Spain. E-mail: edomigo{at}iconcologia.net

Background and Objectives: Single-nucleotide polymorphisms (SNP) in interleukin-10 (IL-10) genes can influence immune responses, which may affect the outcome of patients with lymphoid neoplasms. The aim of this study was to explore the association between polymorphisms of IL-10-_1082A>G and IL-10-_3575T>A with the overall survival in patients with lymphoid neoplasms.

Design and Methods: We analyzed two IL-10 SNP (–1082 and –3575) in 472 consecutive cases with lymphoid neoplasms. Genotypes were tested for association with overall survival and classical prognostic factors by multivariate analysis. Haplotype analysis was carried out using the haplostats package implemented in R software. The implications for survival of patients with lymphoma were evaluated using multivariate analysis.

Results: Lymphoma patients with the IL-10-_3575T>A genotype had a better overall survival (p= 0.002), as did the subgroup with non-Hodgkin’s lymphoma (NHL) (p=0.05). Patients with the IL10_-1082GG genotype had a better median overall survival (p=0.05). When both genotypes were included in a multivariate analysis, IL-10_-3575AA genotype was the only independent prognostic factor for survival (HR=0.20, 95%CI 0.05–0.92). Patients with the IL-10_-1082 and _-3575 G-A/G-A diplotype had a longer overall survival (p=0.003) and this combination appeared to be an independent prognostic factor for survival (HR:0.26; 95%CI 0.08–0.83).

Interpretation and Conclusions: The IL-10_-3575A/A genotype was identified as a marker of favorable survival. Because the IL-10_-1082 and _-3575 G-A/G-A diplotype was also identified as an indicator of longer survival, we cannot exclude the potential additive role of the IL-10_-1082GG genotype. These results need to be replicated in larger series and examined in different NHL subtypes.

Key words: IL-10 polymorphisms, lymphoid neoplasms, survival.