Leukemia Research 36 (2012) 594–597 Contents lists available at SciVerse ScienceDirect Leukemia Research jou rnal h omepa g e: www.elsevier.com/locate/leukres Brief communication Could age modify the effect of genetic variants in IL6 and TNF- genes in multiple myeloma? Alessandro Martino a,d,∗ , Gabriele Buda b , Valentina Maggini c , Francesco Lapi c , Antonella Lupia a , Domenica Di Bello a , Enrico Orciuolo b , Sara Galimberti b , Roberto Barale a , Mario Petrini b , Anna Maria Rossi a a Department of Biology, Genetics division, University of Pisa,Italy b Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University,Italy c Department of Preclinical and Clinical Pharmacology, Interuniversitary Center of Molecular Medicine and Applied Biophysics (CIMMBA), University of Florence, Florence, Italy d German Cancer Research Center (DKFZ), Genomic Epidemiology Group, Heidelberg, Germany a r t i c l e i n f o Article history: Received 17 October 2011 Received in revised form 27 December 2011 Accepted 8 February 2012 Available online 3 March 2012 Keywords: Multiple myeloma Genetic susceptibility Pharmacogenetics SNP Inflammation IL6 TNF-˛ a b s t r a c t Cytokines play a central role in multiple myeloma (MM) pathogenesis thus genetic variations within cytokines coding genes could influence MM susceptibility and therapy outcome. We investigated the impact of 8 SNPs in these genes in 202 MM cases and 235 controls also evaluating their impact on therapy outcome in a subset of 91 patients. Despite the overall negative findings, we found a significant age-modified effect of IL6 and TNF-˛ SNPs, on MM risk and therapy outcome, respectively. Therefore, this observation suggests that genetic variation in inflammation-related genes could be an important mediator of the complex interplay between ageing and cancer. © 2012 Elsevier Ltd. All rights reserved. 1. Introduction Multiple myeloma (MM) is the second most common haemato- logical neoplasm, accounting for 10% of blood cancers and 1% of all cancers. A certain degree of familial aggregation has been observed, suggesting that genetic factors can be involved in the pathogenesis and the evolution of MM [1]. It has been shown that proliferation of normal and malignant plasma cells is under control of a complex network of cytokines, like interleukin (IL)-1, IL2 and its receptor (IL2R), IL3, IL4, IL6 and IL6R, tumour necrosis factor (TNF)-, IL10 and IL11 [2]. There- fore, the relationship between cytokine genetic variability and risk of developing MM or therapy outcome has been widely investi- gated. Nevertheless, results are often controversial and most of the findings failed to be replicated in other studies [3]. ∗ Corresponding author at: German Cancer Research Center (DKFZ) Genomic Epi- demiology Group – C055 Im Neuenheimer Feld 580 D-69120 Heidelberg, Germany (DE). Tel.: +49 6221 42 1814; fax: +49 6221 42 1810. E-mail address: a.martino@dkfz-heidelberg.de (A. Martino). To contribute to clarify the role of cytokine genetic variation in the susceptibility to MM, we selected eight missense or functional SNPs in cytokine coding genes (IL1B rs16944, IL1R1 rs2228139, IL2 rs2069762, IL2RB rs228942, IL6 rs1800797, IL6R rs2228145, TNF˛ rs1800629 and TNFR2 rs1061622) and analyzed the genotype dis- tributions in a case-control study of 202 MM patients and 235 healthy controls. In addition, we evaluated the role of the same variants in relation to therapy response and progression free sur- vival (PFS) after autologous stem cell transplantation (ASCT) in a subgroup of 91 patients that underwent to ASCT after front line treatments. 2. Patients and methods Between September 1992 and November 2009, 202 MM patients were recruited. Two-hundred and thirty five healthy subjects with a comparable age range (35–87) and gender distribution as MM cases were enrolled. Details are given in supplementary methods. Complete follow-up and therapy data concerning ASCT were available for 91 out of 202 MM patients. Subjects with complete or partial response were considered Responders (R), while patients with stable or progressive disease were considered Non Responders (NR). Progression Free Survival (PFS) was calculated as the time (months) from the start of treatment (first ASCT) to disease progression or death 0145-2126/$ – see front matter © 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2012.02.009