The receptor for advanced glycation end products (RAGE) and its ligands are involved in the pathogenesis of cancer. Glyoxalase I (GLO1) is an enzyme which detoxifies advanced glycation end product (AGE) precursors. The aim of the study was to find out the relationship between four polymorphisms (single nucleotide polymorphism, SNP) of the RAGE gene (AGER) and one SNP of the GLO1 gene and clear cell renal cancer (ccRCC). All polymorphisms (rs1800625 RAGE -429T/C, rs1800624 -374T/A, rs3134940 2184A/G, rs2070600 557G/A (G82S), and GLO1 rs4746 419A/C(E111A)) were determined by PCR-RFLP in 214 patients with ccRCC. A group of 154 healthy subjects was used as control. We found significant differences in the allelic and genotype frequencies of GLO1 E111A (419A/C) SNP between patients and controls-higher frequency of the C allele in ccRCC-58.6 vs. 44.5% in controls, OR (95% CI) 1.77 (1.32-2.38), p = 0.0002 (corrected p = 0.001); OR (95% CI) CC vs. AA 2.76 (1.5-4.80), p = 0.0004 (corrected p = 0.002); and AC+CC vs. AA 2.03 (1.23-3.30), p = 0.0034 (corrected p = 0.017). High aggressiveness of the tumor (grade 4) was associated with the presence of C allele RAGE -429T/C SNP (original p = 0.001, corrected p = 0.005) and G allele RAGE 2184A/G SNP (p < 0.001 and p < 0.005), and for genotypes RAGE -429CC (original p = 0.008, corrected p = 0.04) and RAGE 2184GG SNP (original p = 0.005, corrected p = 0.025). Our results demonstrate the link of E111A GLO1 SNP to the presence of the tumor and the connection of RAGE -429T/C and 2184A/G SNPs with the aggressiveness of the tumor. Further studies are required, especially with respect to potential therapeutic implications.

Department of Urology 2nd Faculty of Medicine Charles University Prague and University Hospital Motol 5 Úvalu 84 15006 Prague Czech Republic

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Genes Immun. 2002 May;3(3):123-35 PubMed

Genes Chromosomes Cancer. 2010 Aug;49(8):711-25 PubMed

Urol J. 2010 Winter;7(1):1-9 PubMed

Biochim Biophys Acta. 2007 Oct;1770(10):1468-74 PubMed

J Gastrointest Surg. 2012 Jan;16(1):104-12; discussion 112 PubMed

Cancer Invest. 2009 Jul;27(6):655-60 PubMed

J Clin Invest. 1995 Sep;96(3):1395-403 PubMed

Nephrol Dial Transplant. 2007 Jul;22(7):2020-6 PubMed

Tohoku J Exp Med. 2010 Apr;220(4):291-7 PubMed

Urol Clin North Am. 2003 Nov;30(4):843-52 PubMed

Cancer Invest. 2007 Dec;25(8):720-5 PubMed

Oncol Rep. 2013 Nov;30(5):2365-70 PubMed

Clin Cancer Res. 2008 Jun 1;14(11):3627-32 PubMed

Semin Cell Dev Biol. 2011 May;22(3):318-25 PubMed

Diabetes Care. 1999 Oct;22(10):1745 PubMed

PLoS One. 2013 Sep 10;8(9):e74014 PubMed

Kidney Blood Press Res. 2010;33(1):30-6 PubMed

J Cancer Res Clin Oncol. 2012 Jan;138(1):11-22 PubMed

Carcinogenesis. 2014 Apr;35(4):822-7 PubMed

Diabetes. 2001 Jun;50(6):1505-11 PubMed

Diabetologia. 2007 May;50(5):990-9 PubMed

Clin Biochem. 2010 Jul;43(10-11):882-6 PubMed

Biochem Biophys Res Commun. 1993 Oct 29;196(2):984-9 PubMed

Autism Res. 2011 Aug;4(4):262-70 PubMed

J Clin Invest. 2001 Oct;108(7):949-55 PubMed

Carcinogenesis. 2005 Feb;26(2):293-301 PubMed

Cell Physiol Biochem. 2013;31(4-5):525-31 PubMed

PLoS One. 2012;7(10):e43734 PubMed

Ann N Y Acad Sci. 2008 Apr;1126:268-71 PubMed

J Biol Chem. 1992 Jul 25;267(21):14998-5004 PubMed

J Urol. 2010 Dec;184(6):2254-8 PubMed

Cancer J. 2006 May-Jun;12(3):222-8 PubMed

Arch Med Res. 2008 Apr;39(3):320-5 PubMed

Behav Res Methods. 2007 May;39(2):175-91 PubMed

Biochem Soc Trans. 2003 Dec;31(Pt 6):1343-8 PubMed

Mutat Res. 2005 Nov 11;579(1-2):37-46 PubMed

Anticancer Res. 2012 Aug;32(8):3219-22 PubMed