title: Polymorphisms of the receptor for advanced glycation end-products and glyoxalase I in patients with renal cancer.
abstract: 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.
authors.affiliation: Department of Urology, Second Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Úvalu 84, 15006, Prague, Czech Republic.
authors.forename: Matúš
authors.initials: M
authors.lastname: Chocholatý
authors.forename: Marie
authors.initials: M
authors.lastname: Jáchymová
authors.forename: Marek
authors.initials: M
authors.lastname: Schmidt
authors.forename: Klára
authors.initials: K
authors.lastname: Havlová
authors.forename: Anna
authors.initials: A
authors.lastname: Křepelová
authors.forename: Tomáš
authors.initials: T
authors.lastname: Zima
authors.forename: Marko
authors.initials: M
authors.lastname: Babjuk
authors.forename: Marta
authors.initials: M
authors.lastname: Kalousová
mesh_terms: D000483:Alleles; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D017127:Glycation End Products, Advanced / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D007791:Lactoylglutathione Lyase / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics*
chemical_list: C000593871:AGER protein, human; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; C000597196:GLO1 protein, human; D007791:Lactoylglutathione Lyase