Esophageal cancer is relatively common throughout the world. In 2008, approximately 482,300 new esophageal cancer cases were diagnosed and 406,800 deaths occurred [1]. Notably, almost 90% of cancer cases in the so-called “Esophageal Cancer Belt,” a region stretching from northern Iran through the Central Asian Republics to north-central China, are diagnosed as esophageal squamous cell carcinoma (ESCC). Common risk factors for ESCC include poor nutrition, a lack of adequate vitamin intake, tobacco smoking, excessive alcohol consumption, Barrett's Esophagus and mold pollution, among others [2]. In recent years, hereditary factors have also gained increasing attention for their role in the development of ESCC.
Nicotinamide phosphoribosyl transferase (Nampt) was first identified as pre-B-cell colony enhancing factor (PBEF). The NAMPT gene is located on chromosome7q22, spans 34.7 kb, has 11 exons and 10 introns, and produces cDNA of 2,357 kb translated into a 491-amino acid, 52-kDa protein that stimulates early B-cell formation [3]. Nampt was recently renamed “visfatin”, as it is a visceral, fat-derived adipokine that might mimic insulin function [4], and it may exist both intracellularly (iNampt) and extracellularly (eNampt). Nampt is also known to act as a rate-limiting enzyme in NAD biosynthesis, which is important because NAD availability is crucial for many vital cellular processes, including transcription regulation, DNA repair, cell cycle progression, apoptosis, calcium homeostasis, telomerase activity, antioxidation and oxidative stress, energy metabolism, circadian rhythm maintenance and chromatin dynamics regulation, and regulates factors of genomic stability and organismal metabolic homeostasis, including histone deacetylases (SirT1-T7), COOH-terminal binding proteins, CD38, poly(ADP-ribose) and polymerases [5,6]. Additionally, iNampt is involved in angiogenesis by activating the extracellular signal regulated kinase (ERK) 1/2 pathway and promoting the production of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) 2/9 [7]. Independent of its enzymatic activity, eNampt plays a major role as a cytokine in the regulation of immune response [8]. Nampt is one of a few emerging adipokines (eg. leptin, adiponectin) whose expressions are correlated with the development of a variety of cancers [9]. Furthermore, a series of studies showed that Nampt might be a good biomarker of malignant potential and stage progression [8,10,11].
NAMPT shows a high degree of evolutionary conservation, suggesting that only tiny genetic changes can profoundly affect protein function and its dependent events. To date, the relationship between NAMPT genetic polymorphisms and disease has only been examined in bladder cancer, obesity and acute lung injury [12-14]. The aim of this study was to be the first to explore the relationship between NAMPT genetic polymorphisms and susceptibility to ESCC. Therefore, this case–control study was conducted using subjects recruited in Anyang, China, an area of high ESCC incidence. Three SNPs of NAMPT, including rs61330082 in the promoter region and rs2505568 and rs9034 in the 3’untranslated region (3’ UTR), were selected for this study because of their potential effects on the influence of Nampt expression.