BACKGROUND: Central Europe presents with the highest incidence of sporadic colorectal cancer (CRC) worldwide. As sporadic CRC represents a typical multifactorial disease, it is characterized by intense interaction of the genetic background with the environment. Glutathione S-transferases could act as attractive susceptibility genes for CRC, as they are directly involved in conjugation between glutathione and chemotherapeutics, environmental pollutants and a wide spectrum of xenobiotics. METHODS: In this study, we investigated associations of polymorphisms in glutathione S-transferases (GSTs) genes, that is GSTA1, GSTT1, GSTM1 and GSTP1, with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction. RESULTS: None of investigated polymorphisms showed any associations with CRC, with the exception of GSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC (P = 0.043). CONCLUSIONS: The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability in GST genes is not a major determinant of CRC susceptibility in the Central European population.

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech Republic

Zobrazit více v PubMed

Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N. Colorectal cancer. Lancet. 2010;375(9719):1030–1047. doi: 10.1016/S0140-6736(10)60353-4. PubMed DOI

Conaway CC, Yang YM, Chung FL. Isothiocyanates as cancer chemopreventive agents: their biological activities and metabolism in rodents and humans. Curr Drug Metab. 2002;3:233–255. doi: 10.2174/1389200023337496. PubMed DOI

Yang Y, Yan H, Li Y, Yang ST, Zhang X. Isothiocyanates from Broccolini seeds induce apoptosis in human colon cancer cells: proteomic and bioinformatic analyses. Pharmazie. 2011;66:382–390. PubMed

Coles BF, Chen G, Kadlubar FF, Radominska-Pandya A. Interindividual variation and organ-specific patterns of glutathione S-transferase alpha, mu, and pi expression in gastrointestinal tract mucosa of normal individuals. Arch Biochem Biophys. 2002;403:270–276. doi: 10.1016/S0003-9861(02)00226-6. PubMed DOI

Higgins LG, Hayes JD. Mechanisms of induction of cytosolic and microsomal glutathione transferase (GST) genes by xenobiotics and pro-inflammatory agents. Drug Metab Rev. 2011;43(2):92–137. doi: 10.3109/03602532.2011.567391. Review. PubMed DOI

Ryberg D, Skaug V, Hewer A, Phillips DH, Harries LW, Wolf CR, Ogreid D, Ulvik A, Vu P, Haugen A. Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis. 1997;18:1285–1289. doi: 10.1093/carcin/18.7.1285. PubMed DOI

Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA. Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis. 1998;19:275–280. doi: 10.1093/carcin/19.2.275. PubMed DOI

Brockmoller J, Kerb R, Drakoulis N, Nitz M, Roots I. Genotype and phenotype of glutathione S-transferase class mu isoenzymes mu and psi in lung cancer patients and controls. Cancer Res. 1993;53:1004–1011. PubMed

Van Der Logt EM, Bergevoet SM, Roelofs HM, Van Hooijdonk Z, Te Morsche RH, Wobbes T, De Kok JB, Nagengast FM, Peters WH. Genetic polymorphisms in UDP-glucuronosyltransferases and glutathione S-transferases and colorectal cancer risk. Carcinogenesis. 2004;25:2407–2415. doi: 10.1093/carcin/bgh251. PubMed DOI

Ondrusova M, Muzik J, Hrcka R, Friedova L, Ondrus D. Do we know the cause of the highest colorectal cancer incidence, the changes in the mortality trends and the clinical stages in the Slovak and Czech Republic, the representatives of the Central European region. Neoplasma. 2011;58:283–290. doi: 10.4149/neo_2011_04_283. PubMed DOI

Hlavata I, Vrana D, Smerhovsky Z, Pardini B, Naccarati A, Vodicka P, Novotny J, Mohelnikova-Duchonova B, Soucek P. Association between exposure-relevant polymorphisms in CYP1B1, EPHX1, NQO1, GSTM1, GSTP1 and GSTT1 and risk of colorectal cancer in a Czech population. Oncol Rep. 2010;24:1347–1353. PubMed

Ping J, Wang H, Huang M, Liu ZS. Genetic analysis of glutathione S-transferase A1 polymorphism in the Chinese population and the influence of genotype on enzymatic properties. Toxicol Sci. 2006;89:438–443. doi: 10.1093/toxsci/kfj037. PubMed DOI

Chen CL, Liu Q, Relling MV. Simultaneous characterization of glutathione S-transferase M1 and T1 polymorphisms by polymerase chain reaction in American whites and blacks. Pharmacogenetics. 1997;6:187–191. PubMed

Naveen AT, Adithan C, Padmaja N, Shashindran CH, Abraham BK, Satyanarayanamoorthy K, Anitha P, Gerard N, Krishnamoorthy B. Glutathione S-transferase M1 and T1 null genotype distribution in South Indians. Eur J Clin Pharmacol. 2004;60:403–406. PubMed

Economopoulos KP, Sergentanis TN. STM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: a comprehensive meta-analysis. Eur J Cancer. 2010;46:1617–1631. doi: 10.1016/j.ejca.2010.02.009. PubMed DOI

Vlaykova T, Miteva L, Gulubova M, Stanilova S. Ile105Val GSTP1 polymorphism and susceptibility to colorectal carcinoma in Bulgarian population. Int J Colorectal Dis. 2007;22:1209–1215. doi: 10.1007/s00384-007-0305-z. PubMed DOI

Tijhuis MJ, Wark PA, Aarts JM, Visker MH, Nagengast FM, Kok FJ, Kampman E. GSTP1 and GSTA1 polymorphisms interact with cruciferous vegetable intake in colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev. 2005;14:2943–2951. doi: 10.1158/1055-9965.EPI-05-0591. PubMed DOI

Little J, Sharp L, Masson LF, Brockton NT, Cotton SC, Haites NE, Cassidy J. Colorectal cancer and genetic polymorphisms of CYP1A1, GSTM1 and GSTT1: a case–control study in the Grampian region of Scotland. Int J Cancer. 2006;119:2155–2164. doi: 10.1002/ijc.22093. PubMed DOI