The completion of nine large genome-wide association studies [8, 9] introduced single-nucleotide polymorphisms (SNPs) as risk factors for BC disease [10]. Despite considerable progress, their commercial exploitation in clinical applications remains controversial [11, 12]. In addition, the potential functional influence of specific SNPs on tracer PET uptake needs further investigations in human cancer diseases. Indeed, the first study demonstrating an association between a human SNP (rs3025039 of the Vascular Endothelial

Growth Factor A, abbreviated as VEGFA) and FDG uptake in BC, has included a restricted number of 37 ductal BC patients without metastases [13]. Although, the possible correlation between gene polymorphisms and FDG uptake MK-0457 supplier is considered an innovative and interesting example of translational medicine approach, where information from multiple sources are combined aiming to a more personalized care, the number of INCB28060 cost scientific papers is still limited [13–18]. Nowadays, candidate targets used for these studies are polymorphisms in

the GLUcose Transporter 1 gene (GLUT1 also known as SLC2A1) and the following three hypoxia-related genes: Hypoxia-Inducible Factor 1alpha (HIF-1a), VEGFA and apurinic/apyrimidinic APEX nuclease 1 (APEX1) [13–18]. GLUT family members are often over-expressed in most human malignancies [19] and are involved in tumour initiation and progression. However, they are LY2874455 mouse already present in the respective non-cancerous tissue of origin. The class I transporters (GLUT1), and to a much less extent GLUT3, are the most frequently over-expressed genes in cancer cells. Their over-expression positively correlates with several adverse tumour characteristics and PET uptake in BC [20] and various other malignancies [21–23]. Regarding the role of GLUT1 on PET imaging, only two authors have shown that rs841853and rs710218

GLUT1 SNPs influence tracer PET uptake [14, 15]. These two SNPs were considered to be able to determine variations on the behaviour of the glucose transporter in various human diseases, such as diabetic nephropathy and clear-cell renal carcinoma [24, 25], where a high significant allele frequency in the population investigated was found, suggesting oxyclozanide their potential clinical application. The rs841853 SNP is located in a non-protein coding region (intron 2 of the GLUT1 gene) and seems to have a role in recruiting glucose over the membrane, accelerating growth cell rate. The rs710218 SNP is positioned in the promoter region of the GLUT1 gene adjacent to a putative HIF-1a binding site [26]. HIF-1a controls oxygen delivery and metabolic adaptation to hypoxia via angiogenesis and glycolysis, respectively and it also regulates, under hypoxic conditions, the expression of genes, like the GLUT1 gene.