Advertisement

Molecular Biology Reports

, Volume 38, Issue 6, pp 4181–4184 | Cite as

Paraoxonase 1 192 and 55 polymorphisms in osteosarcoma

  • Arzu ErgenEmail author
  • Onder Kılıcoglu
  • Harzem Ozger
  • Bedia Agachan
  • Turgay Isbir
Article

Abstract

Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stres. Previous studies suggested that involved an amino acid substitution at position 192 gives rise to two alloenzymes with a low activity (Q allele) and a high activity (R allele) towards paraoxon. There also exists a second polymorphism of the human PON1 gene affecting amino acid 55, giving rise to a leucine (L-allele) substitution for methionine (M-allele). PON1 gene polymorphisms were studied in 50 patients with osteosarcoma and 50 healthy controls. Paraoxonase genotypes were determined by PCR–RFLP. We found a reduction in the frequency of PON1 192 R allele in patients (P = 0.015). Besides, PON1 192 wild type QQ genotype (P = 0.015) and PON1 55 wild type L allele (P = 0.001) were higher in patients compared to healthy controls. PON1 192 QQ genotype was associated with osteosarcoma in multivariate logistic regression analysis. Our findings have suggested that PON1 192 wild type genotypes may be associated with a risk of developing osteosarcoma.

Keywords

Paraoxonase Osteosarcoma Risk Polymorphism 

References

  1. 1.
    Cejas P, Casado E, Belda-Iniesta C, De Castro J, Espinosa E, Redondo A, Sereno M, García-Cabezas MA, Vara JA, Domínguez-Cáceres A, Perona R, González-Barón M (2004) Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain). Cancer Causes Control 15:707–719PubMedCrossRefGoogle Scholar
  2. 2.
    Behrend L, Henderson G, Zwacka RM (2003) Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 31:1441–1444PubMedCrossRefGoogle Scholar
  3. 3.
    Costa LG, Cole TB, Jarvik GP, Furlong CE (2003) Functional genomics of the paraoxonase (PON1) polymorphisms: effects on pesticide sensitivity, cardiovascular disease and drug metabolism. Annu Rev Med 54:371–392PubMedCrossRefGoogle Scholar
  4. 4.
    Mackness MI, Mackness B, Durrington PN, Fogelman AM, Berliner J, Lusis AJ, Navab M, Shih D, Fonarow GC (1998) Paraoxonase and coronary heart disease. Curr Opin Lipidol 9(4):319–324PubMedCrossRefGoogle Scholar
  5. 5.
    Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ (1998) Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 394:284–287PubMedCrossRefGoogle Scholar
  6. 6.
    Humbert R, Adler DA, Disteche CM, Omiecinski CJ, Furlong CE (1993) The molecular basis of the human serum paraoxonase polymorphisms. Nat Genet 3:73–76PubMedCrossRefGoogle Scholar
  7. 7.
    Adkins S, Gan KN, Mody M, LaDu 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 53:598–608Google Scholar
  8. 8.
    Ruiz J, Blanche H, James RW, Garin MC, Vaisse C, Charpentier G, Cohen N, Morabia A, Passa P, Froguel P (1995) Gln-Arg192 polymorphism of paraoxonase and coronary heart disease in type 2 diabetes. Lancet 346:869–872PubMedCrossRefGoogle Scholar
  9. 9.
    Akcay MN, Yilmaz I, Polat MF, Akcay G (2003) Serum paraoxonase levels in gastric cancer. Hepatogastroenterology 50(2):cclxxiii–cclxxvGoogle Scholar
  10. 10.
    Akcay MN, Polat MF, Yilmaz I, Akcay G (2003) Serum paraoxonase levels in pancreatic cancer. Hepatogastroenterology 50(2):ccxxv–ccxxviiGoogle Scholar
  11. 11.
    Elkiran ET, Mar N, Aygen B, Gursu F, Karaoglu A, Koca S (2007) Serum paraoxonase and arylesterase activities in patients with lung cancer in a Turkish population. BMC Cancer 7:48PubMedCrossRefGoogle Scholar
  12. 12.
    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 15:1226–1228PubMedCrossRefGoogle Scholar
  13. 13.
    Gallicchio L, McSorley MA, Newschaffer CJ, Huang HY, Thuita LW, Hoffman SC, Helzlsouer KJ (2007) Body mass, polymorphisms in obesity-related genes, and the risk of developing breast cancer among women with benign breast disease. Cancer Detect Prev 31:95–101PubMedCrossRefGoogle Scholar
  14. 14.
    Antognelli C, Mearini L, Talesa VN, Giannantoni A, Mearini E (2005) Association of CYP17, GSTP1, and PON1 polymorphisms with the risk of prostate cancer. Prostate 63:240–251PubMedCrossRefGoogle Scholar
  15. 15.
    Lee CH, Lee KY, Choe KH, Hong YC, Kim YD, Kang JW, Kim H (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 38:345–350Google Scholar
  16. 16.
    Kerridge I, Lincz L, Scorgie F, Hickey D, Granter N, Spencer A (2002) Association between xenobiotic gene polymorphisms and non-Hodgkin’s lymphoma risk. Br J Haematol 118:477–481PubMedCrossRefGoogle Scholar
  17. 17.
    Lincz LF, Kerridge I, Scorgie FE, Bailey M, Enno A, Spencer A (2004) Xenobiotic gene polymorphisms and susceptibility to multiple myeloma. Haematologica 89:628–629PubMedGoogle Scholar
  18. 18.
    Miller SA, Dykes DD, Polesky HS (1988) Simples salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res 16:1215PubMedCrossRefGoogle Scholar
  19. 19.
    Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD 352 and haplotype maps. Bioinformatics 21:263–265PubMedCrossRefGoogle Scholar
  20. 20.
    Ames BN (1983) Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science 221:1256–1264PubMedCrossRefGoogle Scholar
  21. 21.
    Goldstein BD, Witz G (1990) Free radicals and carcinogenesis. Free Radic Res Commun 11:3–10PubMedCrossRefGoogle Scholar
  22. 22.
    Ferre’ N, Camps J, Fernandez-Ballart J, Arija V, Murphy MH, Cerveco S, Biarnes E, Vilella E, Tous M, Joven J (2003) Regulation of serum paraoxonase activity by genetic, nutritional, and lifestyle factors in the general population. Clin Chem 49(9):1491–1497CrossRefGoogle Scholar
  23. 23.
    Mackness B, Durrington PN, Mackness MI (1998) Human serum paraoxonase. Gen Pharmacol 31(3):329–336PubMedCrossRefGoogle Scholar
  24. 24.
    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(6):1226–1228PubMedCrossRefGoogle Scholar
  25. 25.
    Rajaraman P, Hutchinson A, Rothman N, Black PM, Fine HA, Loeffler JS, Selker RG, Shapiro WR, Linet MS, Inskip PD (2008) Oxidative response gene polymorphisms and risk of adult brain tumors. Neuro Oncol 10:709–715PubMedCrossRefGoogle Scholar
  26. 26.
    Lurie G, Wilkens LR, Thompson PJ, McDuffie KE, Carney ME, Terada KY, Goodman MT (2008) Genetic polymorphisms in the paraoxonase 1 gene and risk of ovarian epithelial carcinoma. Cancer Epidemiol Biomarkers Prev 17(8):2070–2077PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Arzu Ergen
    • 1
    Email author
  • Onder Kılıcoglu
    • 2
  • Harzem Ozger
    • 2
  • Bedia Agachan
    • 1
  • Turgay Isbir
    • 3
  1. 1.Department of Molecular Medicine, Institute of Experimental MedicineIstanbul UniversityCapa, IstanbulTurkey
  2. 2.Department of Orthopaedics and Traumatology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey
  3. 3.Department of Medical BiologyYeditepe UniversityIstanbulTurkey

Personalised recommendations