- Volume 16 Issue 2
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Association of Paraoxonase-1(Q192R and L55M) Gene Polymorphisms and Activity with Colorectal Cancer and Effect of Surgical Intervention
- Ahmed, Nagwa S. (Department of Medical Biochemistry, Faculty of Medicine, Tanta University) ;
- Shafik, Noha M. (Department of Medical Biochemistry, Faculty of Medicine, Sohag University) ;
- Elraheem, Omar Abd (General Surgery, Faculty of Medicine, Sohag University) ;
- Abou-Elnoeman, Saad-Eldin A. (Department of Medical Biochemistry, Faculty of Medicine, Sohag University)
- Published : 2015.02.25
Background: Colorectal cancer (CRC) is a leading cause of cancer-related death. Oxidative DNA damage may contribute to cancer risk and the antioxidant paraoxonase is one endogenous free radical scavenger in the human body which could therefore exert an influeence. Purpose: Aim of this study was to determine the role of serum arylesterase (ARE) and paraoxonase 1(PON1) activities in CRC patients and to find any association between (PON1) Q192R and L55M gene polymorphisms in CRC patients. Also the serum ARE and PON1 activities in CRC patients will be investigated before and after surgery Materials and Methods: This study involved a total of 50 patients with newly diagnosed CRC and 80 healthy controls. PON1 and ARE activities were determined using an enzymatic spectrophotometric method. PON1 Q192R and L55M gene polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based restriction fragment analysis. The restriction enzyme AlwI was used to examine the Q192R polymorphism and Hsp92II for the L55M polymorphism. Results: Significant differences in the PON1 Q192R polymorphism were found between patients and controls. The Q allele was more frequent in the patient group than in controls, while the R allele was more frequent in the controls. Significant differences were found in the L55M polymorphism. Additionally, there were significant differences in L and M allele frequencies (p=0.001). The serum activities of PON1 and ARE were low in QQ and MM genotype. Conclusions: serum PON1 and ARE activities were significantly lower in CRC patients compared to healthy subjects. The R allele may protect against colorectal cancer.
- Aiello M, Vella N, Cannavo C, et al (2011). Role of genetic polymorphisms and mutations in colorectal cancer therapy. Mol Med Rep, 4, 203-8.
- Akkiz H, Kuran s, Akgollu e, et al (2013). Effect of PON1 gene polymorphisms in Turkish patients with hepatocellular carcinoma. Meta Gene, 1, 93-101. https://doi.org/10.1016/j.mgene.2013.09.007
- Aksoy-Sagirli P, Cakmakoglu B, Isbir T, et al (2011): Paraoxonase-1 192/55 polymorphisms and the risk of lung cancer in a Turkish population. Anticancer Res, 31, 2225-30.
- Alkhouri RH, Baker SS, Hashmi H, Liu W, Baker RD, Zhu L (2014): Paraoxonase gene expression in pediatric inflammatory bowel disease. Clin Cell Immunol, 5, 3.
- Antognelli C, Mearini L, Talesa VN, Giannantoni A, et al (2005). Association of CYP17, GSTP1, and PON1 polymorphisms with the risk of prostate cancer. Prostate, 63, 240-251 https://doi.org/10.1002/pros.20184
- Arpaci A, 36355Gormus U, 55Dalan B, 55Berkman S, 55Isbir T (2009): Investigation of PON1 192 and PON1 55 polym
- Aviram M, Hardak E, Vaya J, et al (2000). Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities. Circulation, 101, 2510-7. https://doi.org/10.1161/01.CIR.101.21.2510
- Balci H, Genc H, Papila C, et al (2012). Serum lipid hydroperoxide levels and paraoxonase activity in patients with lung, breast, and colorectal cancer. J Clin Lab Anal, 26, 155-60. https://doi.org/10.1002/jcla.21503
- Bulbuller N, Eren E, Ellidag HY, et al (2013): Diagnostic value of thiol paraoxonase 1, arylesterase and oxidative balance in colorectal cancer in human. Neoplasma, 60, 419-24. https://doi.org/10.4149/neo_2013_054
- Connolly JL, Schnitt SJ, Wang HH, Longtine JA, et al (2003). Principles of cancer pathology. in: Cancer Medicine (Kufe DW, Pollock RE and Weichselbaum RR, eds.). Hamilton-BC Decker, London, 487-502.
- Costa LG, Cole TB, Furlong CE (2003). Polymorphisms of paraoxonase (PON1) and their significance in clinical toxicology of organophosphates. J Toxicol Clin Toxicol, 41, 37-45. https://doi.org/10.1081/CLT-120018269
- Aaltonen L, Johns L, Jarvinen H, et al (2007). Explaining the familial colorectal cancer risk associated with mismatch repair (MMR)-deficient and MMR-stable tumors. Clin Cancer Res, 13, 356-61. https://doi.org/10.1158/1078-0432.CCR-06-1256
- Adkins S, Gan KN, Mody M, La Du BN (1993). Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes. Am J Hum Genet, 52, 598-608.
- Davies HG, Richter RJ, Keifer M, Broomfield CA, Sowalla J, Furlong CE (1996). The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin. Nat Genet, 14, 334-6. https://doi.org/10.1038/ng1196-334
- Deakin SP, James RW (2004). Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme, paraoxonase-1. Clin Sci, 107, 435-47. https://doi.org/10.1042/CS20040187
- De Roos AJ, Gold LS, Wang S, et al (2006): Metabolic gene variants and risk of non-Hodgkin's lymphoma. Cancer Epidemiol Biomarkers Prev, 15, 1647-53. https://doi.org/10.1158/1055-9965.EPI-06-0193
- Draganov DI, La Du BN (2004). Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedebergs Arch Pharmacol, 369, 78. https://doi.org/10.1007/s00210-003-0833-1
- Eckerson HW, Wyte CM, La Du BN (1983). The human serum paraoxonase/arylesterase polymorphism. Identification of phenotypes by their response to salts. Am J Hum Genet, 35, 214-27.
- Ellidag HY, Eren EO, Neselioglu S, Yilmaz NJ (2014). Phenotype distribution of paraoxonase-1 in patients with multiple myeloma, bladder, and colorectal cancer. Med Biochem, 33, 1-7. https://doi.org/10.2478/jomb-2014-0006
- Ergen A, Kilicoglu O, Ozger H, et al (2011). Paraoxonase 1 192 and 55 polymorphisms in osteosarcoma. Mol Biol Rep 38, 4181-4. https://doi.org/10.1007/s11033-010-0538-8
- Ferre N, Camps J, Fernandez-Ballart J, et al (2003). Regulation of serum paraoxonase activity by genetic, nutritional and lifestyle factors in the general population. Clin Chem, 49, 1491-7. https://doi.org/10.1373/49.9.1491
- Fossati P, Prencipe L (1982). Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem, 28, 2077-80.
- Friedewald W, Levy R, Fedrickson D (1972): Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem, 18, 499-502.
- Gallicchio L, McSorley MA, Newschaffer CJ, et al (2007). Body mass, polymorphisms in obesity-related genes, and the risk of developing breast cancer among women with benign breast disease. Cancer Detect Prev, 31, 95-101. https://doi.org/10.1016/j.cdp.2007.02.004
- Gold LS, De Roos AJ, Brown EE, et al (2009): Associations of common variants in genes involved in metabolism and response to exogenous chemicals with risk of multiple myeloma. Cancer Epidemiol, 33, 276-80. https://doi.org/10.1016/j.canep.2009.08.005
- Grove H (1979). Effect of reagent pH on determination of HDL cholesterol by precipitation with sodium phosphotungstatemagnesium. Clin Chem, 25, 560.
- Hristozov D, Gadjeva V, Vlaykova T, Dimitrov G (2001). Evaluation of oxidative stress in patients with cancer. Arch Physiol Biochem.109 (4):331-6. https://doi.org/10.1076/apab.109.4.331.4248
- Hu Y, Wang JL, Tao HT, et al (2013). Expression and significance of TSGF, CEA and AFP in patients before and after radical surgery for colon cancer. Asian Pac J Cancer Prev, 14, 3877-80. https://doi.org/10.7314/APJCP.2013.14.6.3877
- Jayakumari N, Thejaseebai G (2009). High prevalence of low serum paraoxonase-1 in subjects with coronary artery disease. J Clin Biochem Nutr, 45, 278-84. https://doi.org/10.3164/jcbn.08-255
- Kilic SS, Aydin S, Kilic N, et al (2005). Serum arylesterase and paraoxonase activity in patients with chronic hepatitis. World J Gastroenterol, 11, 7351-4. https://doi.org/10.3748/wjg.v11.i46.7351
Kumon Y, Suehiro T, Ikeda Y, Hashimoto K (2003). Human paraoxonase-1 gene expression by HepG2 cells is downregulated by interleukin-
$1\beta$and tumor necrosis factor- $\alpha$, but is upregulated by interleukin-6. Life Sci, 73, 2807-15. https://doi.org/10.1016/S0024-3205(03)00704-5
- Lee CH, Lee KY, Choe KH, et al (2005). Effects of oxidative DNA damage induced by polycyclic aromatic hydrocarbons and genetic polymorphism of the paraoxonase-1 (PON1) gene on lung cancer. J Prev Med Pub Health, 38, 345-50.
- Li HL, Liu DP, Liang CC (2003). Paraoxonase gene polymorphisms, oxidative stress, and diseases. J Mol Med, 81, 766-79. https://doi.org/10.1007/s00109-003-0481-4
- Lichtenstein P, Holm NV, Verkasalo PK, et al (2000). Environmental and heritable factors in the causation of cancer-analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med, 343, 78-85. https://doi.org/10.1056/NEJM200007133430201
- Lincz LF, Kerridge I, Scorgie FE, Bailey M, Enno A, Spencer A (2004): Xenobiotic gene polymorphisms and susceptibility to multiple myeloma. Haematologica, 89 (5): 628-629.
- Loft S, Moller P, Cooke MS, Rozalski R, Olinski R (2008). Antioxidant vitamins and cancer risk: is oxidative damage to DNA a relevant biomarker? Eur J Nutr, 47 Suppl 2, 19-28. https://doi.org/10.1007/s00394-008-2004-0
- Lurie G, Wilkens LR, Thompson PJ, et al (2008). Genetic polymorphisms in the paraoxonase 1 gene and risk of ovarian epithelial carcinoma. Cancer Epidemiol Biomarkers Prev, 17, 2070-7. https://doi.org/10.1158/1055-9965.EPI-08-0145
- Mackness MI, Harty D, Bhatnagar D, et al (1991). Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus. Atherosclerosis, 86, 193-9. https://doi.org/10.1016/0021-9150(91)90215-O
- Mackness B, Mackness MI, Arrol S, Turkie W, Durrington PN (1997). Effect of the molecular polymorphisms of human paraoxonase (PON1) on the rate of hydrolysis of paraoxon. Br J Pharmacol, 122, 265-8. https://doi.org/10.1038/sj.bjp.0701390
- Nevin DN, Zambon A, Furlong CE, et al (1996). Paraoxonase genotypes, lipoprotein lipase activity, and HDL. Arterioscler Thromb Vasc Biol, 16, 1243-9. https://doi.org/10.1161/01.ATV.16.10.1243
- Ozturk O, Kagnici OF, Ozturk T, et al (2009). 192R allele of paraoxanase 1 (PON1) gene as a new marker for susceptibility to bladder cancer. Anticancer Res, 29, 4041-6.
- Richmond W (1973). Enzymatic determination of cholesterol. Clin Chem, 19, 1350-6.
- Stevens VL, Rodriguez C, Pavluck AL, Thun MJ, Calle EE (2006). Association of polymorphisms in the paraoxonase 1 gene with breast cancer incidence in the CPS-II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev, 15, 1226-8. https://doi.org/10.1158/1055-9965.EPI-05-0930
- Unal E, Eris C, Kaya B, et al (2012). Paraoxonase and arylesterase activities, lipid profile, and oxidative damage in experimental ischemic colitis model. Gastroenterol Res Pract, 97, 950-6.
- Van Der Logt EM, Janssen CH, Van Hooijdonk Z, et al (2005). No association between genetic polymorphisms in NAD(P) H oxidase p22phox and paraoxonase 1 and colorectal cancer risk. Anticancer Res, 25, 1465-70.
- Vecka M, Jachymova M, Vavrova L, et al (2012): Paraoxonase-1 (PON1) status in pancreatic cancer: relation to clinical parameters. Folia Biol, 58, 231-7.
- Vermorken AJ, Zhu J, Andres E (2014): Obesity and colorectal cancer risk: the role of oxidative stress. Gut, 63, 529-30. https://doi.org/10.1136/gutjnl-2013-305561
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