title: Genotyping analysis and ¹⁸FDG uptake in breast cancer patients: a preliminary research.
abstract: BACKGROUND
  Diagnostic imaging plays a relevant role in the care of patients with breast cancer (BC). Positron Emission Tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) has been widely proven to be a clinical tool suitable for BC detection and staging in which the glucose analog supplies metabolic information about the tumor. A limited number of studies, sometimes controversial, describe possible associations between FDG uptake and single nucleotide polymorphisms (SNPs). For this reason this field has to be explored and clarified. We investigated the association of SNPs in GLUT1, HIF-1a, EPAS1, APEX1, VEGFA and MTHFR genes with the FDG uptake in BC.
  
  
  METHODS
  In 26 caucasian individuals with primary BC, whole-body PET-CT scans were obtained and quantitative analysis was performed by calculating the maximum Standardized Uptake Value normalized to body-weight (SUVmax) and the mean SUV normalized to body-weight corrected for partial volume effect (SUVpvc). Human Gene Mutation Database and dbSNP Short Genetic Variations database were used to analyze gene regions containing the selected SNPs. Patient genotypes were obtained using Sanger DNA sequencing analysis performed by Capillary Electrophoresis.
  
  
  RESULTS
  BC patients were genotyped for the following nine SNPs: GLUT1: rs841853 and rs710218; HIF-1a: rs11549465 and rs11549467; EPAS1: rs137853037 and rs137853036; APEX1: rs1130409; VEGFA: rs3025039 and MTHFR: rs1801133. In this work correlations between the nine potentially useful polymorphisms selected and previously suggested with tracer uptake (using both SUVmax and SUVpvc) were not found.
  
  
  CONCLUSIONS
  The possible functional influence of specific SNPs on FDG uptake needs further studies in human cancer. In summary, this is the first pilot study, to our knowledge, which investigates the association between a large panel of SNPs and FDG uptake specifically in BC patients. This work represents a multidisciplinary and translational medicine approach to study BC where, the possible correlation between SNPs and tracer uptake, may be considered to improve personalized cancer treatment and care.
authors: IBFM CNR - LATO, Cefalù, PA, Italy. valentina.bravata@polooncologicocefalu.it
authors: Valentina
authors: V
authors: Bravatà
authors: Alessandro
authors: A
authors: Stefano
authors: Francesco P
authors: FP
authors: Cammarata
authors: Luigi
authors: L
authors: Minafra
authors: Giorgio
authors: G
authors: Russo
authors: Stefania
authors: S
authors: Nicolosi
authors: Sabina
authors: S
authors: Pulizzi
authors: Cecilia
authors: C
authors: Gelfi
authors: Maria C
authors: MC
authors: Gilardi
authors: Cristina
authors: C
authors: Messa
mesh_terms: D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005838:Genotype; D006801:Humans; D064847:Multimodal Imaging; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
references: Kidney Int. 2001 Mar;59(3):985-9
references: 11231353
references: Arch Med Sci. 2011 Feb;7(1):134-7
references: 22291746
references: Mol Membr Biol. 2011 Apr;28(3):182-6
references: 21332301
references: Prostate. 2005 May 15;63(3):215-21
references: 15538748
references: Breast Cancer Res Treat. 2007 Sep;104(3):299-308
references: 17063264
references: Nat Genet. 2009 May;41(5):579-84
references: 19330030
references: Curr Opin Genet Dev. 1998 Oct;8(5):588-94
references: 9794818
references: Clin Nucl Med. 2012 Feb;37(2):121-7
references: 22228332
references: J Nucl Med. 2007 Jun;48(6):932-45
references: 17504879
references: J Cell Physiol. 2005 Mar;202(3):654-62
references: 15389572
references: JAMA. 2008 Mar 19;299(11):1353-5
references: 18349097
references: Trends Mol Med. 2002;8(4 Suppl):S62-7
references: 11927290
references: J Med Genet. 2003 Aug;40(8):619-25
references: 12920077
references: Mol Psychiatry. 2008 Nov;13(11):1021-7
references: 18414408
references: Genes Dev. 2006 Mar 1;20(5):557-70
references: 16510872
references: OMICS. 2013 Mar;17(3):119-29
references: 23421906
references: J Nucl Med. 2010 Aug;51(8):1191-7
references: 20679470
references: J Nucl Med. 1996 Jun;37(6):1042-7
references: 8683298
references: Methods Mol Biol. 2000;132:365-86
references: 10547847
references: Nat Genet. 2003 Dec;35(4):331-40
references: 14608355
references: Hum Mol Genet. 2007 Oct 1;16(19):2333-40
references: 17855454
references: Eur J Nucl Med Mol Imaging. 2010 Aug;37(9):1679-87
references: 20422184
references: J Natl Cancer Inst. 2009 Jul 15;101(14):973-5
references: 19567420
references: N Engl J Med. 2009 Apr 23;360(17):1696-8
references: 19369660
references: BMC Res Notes. 2012 Jul 03;5:343
references: 22759679
references: Diabetes. 2005 Dec;54(12):3587-91
references: 16306381
references: Nat Genet. 2007 Jul;39(7):870-4
references: 17529973
references: Ann Nucl Med. 2008 Oct;22(8):699-705
references: 18982473
references: Cancer Genet Cytogenet. 2005 Dec;163(2):151-5
references: 16337858
references: J Clin Oncol. 2006 May 10;24(14):2137-50
references: 16682732
references: Nat Rev Genet. 2006 Oct;7(10):781-91
references: 16983374
references: Expert Rev Mol Diagn. 2010 Jan;10(1):65-74
references: 20014923
references: Breast Cancer Res Treat. 2004 Dec;88(3):205-8
references: 15609122
references: Mol Imaging Biol. 2011 Feb;13(1):178-86
references: 20449668
references: J Exp Clin Cancer Res. 2010 Jun 12;29:69
references: 20540786
references: J Breast Cancer. 2012 Jun;15(2):148-56
references: 22807931
references: Br J Cancer. 2009 May 19;100(10):1680-6
references: 19367277
references: Circ Res. 2008 May 9;102(9):1075-81
references: 18356544
references: Histopathology. 2008 Jan;52(1):67-81
references: 18171418
references: Expert Rev Mol Diagn. 2010 May;10(4):417-34
references: 20465497
references: Am J Clin Oncol. 2008 Aug;31(4):352-62
references: 18845994
references: J Cancer Res Clin Oncol. 2008 Feb;134(2):227-36
references: 17653575
references: Am J Pathol. 2000 Aug;157(2):411-21
references: 10934146
references: Lung Cancer. 2006 Sep;53(3):257-62
references: 16837101