300 J Contemp Med Sci | Vol. 3, No. 12, Autumn 2017: 300–305 Research Department of Molecular and Medical Biotechnology, College of Biotechnology, Al-Nahrain University, Aljadriya, Baghdad, Iraq. Correspondence to: Hassan Mohammad Naif (e-mail: drnaifhassan@gmail.com). (Submitted: 27 August 2017 – Revised version received: 02 September 2017 – Accepted: 11 October 2017 – Published online: 26 December 2017) Objective Non-Hodgkin lymphomas are a diverse lymphoid neoplasms and it is the sixth most common cancer in the world, but it is well established that immune dysregulation especially by cytokines is one of major risk factors. This study investigates the association of genetic polymorphisms of IL-12p401188A/C and its circulating serum measurement in patients with advanced stage of NHLs in Iraq. Methods Fifty-fve confrmed patients with advanced stages of NHLs and 40 apparently healthy individuals were used. Genetic polymorphism and circulating levels of IL-12p40 were examined by allele-specifc polymerase chain reaction (AS-PCR) using specifc primers and ELISA, respectively. Results The results of SNP IL-12p40 1188A>C had three genotypes, which were AA, AC and CC. These genotypes represented 32.73%, 38.18% and 29.09%, respectively, among NHL patients and 52.5%, 37.5% and 10%, respectively, among controls with a signifcant diference for the homozygous mutant genotype (OR = 4.667, 95% CI = 1.319–16.512, P = 0.017). Serum levels of IL-12p40 were signifcantly increased in an allele-dependent manner, which was linked to the CC homozygosity as being the highest. Conclusions This study has revealed a signifcant correlation between the gene polymorphisms of IL-12p40 and the induction of serum IL-12 with the risk to poor prognosis in patients with NHL. The correlation with the NHL grades and the prognostic value warrant further progressive investigation of developing prognostic biomarkers for NHL using patients at various disease stages. Keywords non-Hodgkin’s lymphoma, single nucleotide polymorphism, IL-12, allele-specifc PCR Introduction Non-Hodgkin lymphomas are a diverse group of mature lymphoid neoplasms with a wide range of cellular, histo- logic presentations, cells of origin and etiologies. 1 Numerous environmental and genetic factors have been documented to be associated with the incidence of NHLs, however the exact causes are beyond the current knowledge. 2 Regardless of causes, the integrity of the immune system represents the cornerstone in the resistance or progression of the disease. Many disorders of this system such as immune deficiency and autoimmune disease like rheumatoid arthritis and systemic lupus erythematosus are reported to predispose to NHLs. 3 Interleukin-12 (IL-12) is among the main proinfammatory cytokines of the immune system. IL-12 is a multifunctional cytokine acting as a key regulator by inducing and maintaining T helper 1, which bridges innate and adaptive immunity, 4 and mediates immune response in several types of cancers, 5,6 and its p70 subunit is associated with NHL. 7 It is a heterodimeric proinfammatory cytokine formed by a 35,000-dalton light (p35) and a 40,000-dalton heavy chain (p40), which are encoded by the IL-12A and IL-12B genes, respectively, and mapped to human chromosomes 3p12-q13.2 and 5q31-33. 8 IL-p40 (IL-12B) encodes the p40 subunit of both pathways of IL-12 and IL-23. 9 Te inherited variations in IL-12p40 and IL-12p70 genes that could modulate cancer susceptibility, and as a consequence possess predictive, therapeutic or prognostic implications. 10 Following the discovery of IL-12, three other members (IL-23, IL-27, and IL-35) have been added to the IL-12 family and shown to play critical roles in T1 cell functions. 11,12 Several single nucleotide polymorphisms have been iden- tifed in the IL-12 gene such as 3’UTR 1188 A/C polymor- phism, which is associated with diferent diseases. Several polymorphisms have been described in the promoter region, 13 and in the 3’ untranslated region (UTR) of IL-12 p40 gene, IL-12B. 14 In this study, we hypothesized that potential func- tional polymorphisms IL-12p40 may contribute to risk of NHL in population from Iraq. Hence, SNPs in IL-12p40 gene was examined to assess its efect on the susceptibility to NHLs. Materials and Methods Study Subjects Tis case control study included 55 patients with confrmed NHLs during the period from January 2015 to December 2015 from six teaching hospitals and medical centers in Baghdad Medical City (Teaching Hospital of Pediatric, Baghdad teaching Hospital and Hematology Center, Al-Mustansiriya University, Al-Kadhimyia Teaching Hospital). Family unrelated, appar- ently healthy 35 individuals were randomly selected to repre- sent the control group. Te mean ages of patients and control were 33.45 and 36.49 years, respectively. Te stage of NHL dis- ease of those recruited patients was mainly at the advanced stage of disease, so results will indicate this stage as such with no treatment history. Tis research was approved by the Ethics Committee of Scientifc Research of the University. An informed consent to take part in the study was obtained from each participant afer receiving approval of the experimental protocol by the Ethics Committee, which was essentially in line with the principles of the Declaration of Helsinki. ISSN 2413-0516 Association of gene polymorphism and serum levels of IL-12p40 with the susceptibility to non-Hodgkin’s lymphoma in Iraq Hassan Mohammad Naif