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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4894-4895.
CORRESPONDENCE To the editor:The interleukin-10 gene promoter polymorphism (-1082) does not correlate with clinical outcome in diffuse large B-cell lymphomaInterleukin-10 (IL-10) is a cytokine important in suppressing the immune response by inhibiting proinflammatory cells. However, this cytokine is multifunctional and can also stimulate proliferation as has been shown both in normal and tumor B cells.1 IL-10 has been implicated to play a role in lymphoma development, especially considering the finding of an association between increased IL-10 levels and poor outcome in some lymphoma entities.1,2 Furthermore, IL-10 gene promoter polymorphisms have been shown to affect the levels of IL-10 expression, for example, the IL-10-1082A and IL-10-1082G alleles correlate with low and high IL-10 production, respectively.3 Recently, Lech-Maranda et al2 reported that the IL-10-1082 genotype influenced clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL), where an improved overall survival and a higher rate of complete remission were found for patients with IL-10-1082AG/GG genotypes compared with patients with IL-10-1082AA genotype. They also showed a higher IL-10-1082G allele frequency in DLBCL compared with healthy controls (0.47 vs 0.39). To investigate this further, we screened 244 samples obtained from patients with DLBCL (168 with de novo DLBCL, 67 with DLBCL and previous history of low-grade lymphoma, and 9 with DLBCL and unknown previous history) from Uppsala and Umeå University Hospitals to establish their IL-10-1082 genotype and compare it with overall survival. We also assessed the genotype in 195 healthy controls. In the present analysis, the frequency of the IL-10-1082G allele was not significantly different in our patients with DLBCL versus the control group (0.43 vs 0.46; P = .38). Thus, the increased IL-10-1082G allele frequency could not be verified in our analysis of DLBCL (Table 1). Furthermore, we did not find any difference in overall survival between the 174 patients with IL-10-1082AG/GG genotype and the 70 patients with IL-10-1082AA (median survival, 39 vs 37 months; log-rank test, P = .50; Figure 1). No significant difference in the clinical presentation was indicated between the 2 cohorts considering sex, clinical stage, complete remission rate, and international prognostic index. Although patients in our analysis, in general, were older ( 2; P = .014), had B symptoms more often (2; P = .034), and had elevated serum lactate dehydrogenase (S-LDH; P = .012) levels, no difference in survival was shown between patients with IL-10-1082AG/GG and IL-10-1082AA genotype when considering only patients younger than 60 years of age or when patients with or without B symptoms or elevated S-LDH levels were analyzed separately. Moreover, no difference in outcome was evident for patients with or without the IL-10-1082G allele when separately analyzing de novo DLBCL and cases with previous history of low-grade lymphoma. In conclusion, we could not confirm the findings in the report by Lech-Maranda et al2 of increased frequency of the IL-10-1082G allele and its association with superior outcome in our analysis of patients with DLBCL. We therefore believe that the clinical relevance of the IL-10-1082 promoter polymorphism may be limited in DLBCL, although larger studies have to be performed to conclude this properly.
Acknowledgements
The authors are grateful to Drs Lars Klareskog and Leonid Padyukov and to the Epidemiologic investigation of rheumatoid arthritis (EIRA) group for help with the collection of the healthy control material and to Dr Thomas Axelsson for technical assistance. The single nucleotide polymorphism (SNP) genotyping was performed by the Wallenberg Consortium North (WCN) SNP platform, Department of Medical Sciences, Uppsala University.
Correspondence: Mattias Berglund, Departments of Oncology, Radiology, and Clinical Immunology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden; e-mail: Mattias.Berglund{at}genpat.uu.se. References
Response:Different patients, different results: the need for prospective controlled studiesIn this issue, Berglund and colleagues report their analysis of the IL-10 gene polymorphism (IL10-1082) in a series of 244 lymphoma patients. This series included 168 de novo diffuse large B-cell lymphomas whereas other cases had a previous history of low-grade lymphoma and should probably be considered as transformed lymphoma. The authors did not find a different distribution in IL10-1082 alleles between the patient and the control populations. Of note, the IL10-1082G allele disequilibrium frequency that we previously described only applies to diffuse large B-cell lymphoma and not to other lymphoma subtypes (E.W. and G.S., unpublished results, May 2005). In this context, these authors also failed to observe a prognostic significance for the IL10-1082 G allele in diffuse large B-cell lymphoma.The reasons for this discrepancy are unclear and may include several biases such as patient characteristics and treatment options and results. For instance, the median survival reported by Berglund et al is close to 38 months for the whole population but was projected to be 70 months in our study. The fact that this study includes older patients is also significant since the prognostic significance of the IL10-1082 G allele was more pronounced in patients younger than 60 years than in older patients in our study. Finally, how inherited immune response may actually influence patient outcome may indeed depend of the initial characteristics of the patient, the disease, and the efficiency of treatment. Altogether, these results emphasize the need for prospective and multicentric genomic DNA collection linked to a clinical database, such as the one currently built with Groupe d'Etude des Lymphomes de l'Adulte (GELA) clinical trials, which will be analyzed in the coming years.
Correspondence: Centre Hospitalier Leon-SUD, 69495 Pierre-Bénite cedex, France; e-mail: gilles.salles{at}chu-lyon.fr.
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