Skip to main content

Advertisement

Log in

The effects of NOS3 Glu298Asp variant on colorectal cancer risk and progression in Turkish population

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Endothelial nitric oxide synthase (eNOS), coded by the gene NOS3, may play an important role in uncontrollable cellular growth in several cancer types. Our study was performed to test the association between Glu298Asp polymorphisms in the NOS3 gene and colorectal cancer risk and progression. In this study, NOS3 Glu298Asp polymorphism was genotyped in 84 patients with colorectal cancer and 99 healthy subjects using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis. There were significant differences in the distribution of NOS3 genotypes and frequencies of the alleles between colorectal cancer patients and controls (P = 0.016, P = 0.006, respectively). The increased frequency of NOS3 Glu298Asp homozygotes genotypes in patients who had advanced tumour stage was statistically significant (P = 0.042). Our findings have suggested that NOS3 Glu298Asp polymorphism might be associated with the risk and progression of colorectal cancer in Turkish population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Potter JD (1999) Related colorectal cancer: molecules and populations. J Natl Cancer Inst 91:916–932

    Article  PubMed  CAS  Google Scholar 

  2. Ames BN (1983) Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science 221:1256–1264

    Article  PubMed  CAS  Google Scholar 

  3. Pfeifer GP, Denissenko MF, Olivier M, Tretyakova N, Hecht SS, Hainaut P (2002) Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene 21:7435–7451

    Article  PubMed  CAS  Google Scholar 

  4. Wink DA, Vodovotz Y, Laval J, Laval F, Dewhirst MW, Mitchell JB (1998) The multifaceted roles of nitric oxide in cancer. Carcinogenesis 19:711–721

    Article  PubMed  CAS  Google Scholar 

  5. Thomsen LL, Lawton FG, Knowles RG, Beesley JE, Riveros-Moreno V, Moncada S (1994) Nitric oxide synthase activity in human gynecological cancer. Cancer Res 54:52–413

    Google Scholar 

  6. Thomsen LL, Miles DW, Happerfield L, Bobrow LG, Knowles RG, Moncada S (1995) Nitric oxide synthase activity in human breast cancer. Br J Cancer 72:41–44

    Article  PubMed  CAS  Google Scholar 

  7. Cobbs CS, Brenman JE, Aldape KD, Bredt DS, Israel MA (1995) Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res 55:727–730

    PubMed  CAS  Google Scholar 

  8. Kimura H, Esumi H (2003) Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis. Acta Biochim Pol 50:49–59

    PubMed  CAS  Google Scholar 

  9. Xu W, Charles IG, Moncada S, Gorman P, Sheer D, Liu L, Emson P (1994) Mapping of the genes encoding human inducible and endothelial nitric oxide synthase (NOS2 and NOS3) to the pericentric region of chromosome 17 and to chromosome 7, respectively. Genomics 21:419–422

    Article  PubMed  CAS  Google Scholar 

  10. Rossi GP, Cesari M, Zanchetta M, Colonna S, Maiolino G, Pedon L, Cavallin M, Maiolino P, Pessina AC (2003) The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study. J Am Coll Cardiol 41:930–937

    Article  PubMed  CAS  Google Scholar 

  11. Awata T, Neda T, Iizuka H, Kurihara S, Ohkubo T, Takata N, Osaki M, Watanabe M, Nakashima Y, Sawa T, Inukai K, Inoue I, Shibuya M, Mori K, Yoneya S, Katayama S (2004) Endothelial nitric oxide synthase gene is associated with diabetic macular edema in type 2 diabetes. Diabetes Care 27:2184–2190

    Article  PubMed  CAS  Google Scholar 

  12. Medeiros R, Morais A, Vasconcelos A, Costa S, Pinto D, Oliveira J, Lopes C (2002) Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility to prostate cancer. Eur J Cancer Prev 11:343–350

    Article  PubMed  CAS  Google Scholar 

  13. Riener EK, Hefler LA, Grimm C, Galid A, Zeillinger R, Tong-Cacsire D, Gitsch G, Leodolter S, Tempfer CB (2004) Polymorphisms of the endothelial nitric oxide synthase gene in women with vulvar cancer. Gynecol Oncol 93:686–690

    Article  PubMed  CAS  Google Scholar 

  14. Hefler LA, Ludwig E, Lampe D, Zeillinger R, Leodolter S, Gitsch G, Koelbl H, Tempfer CB (2002) Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer. Gynecol Oncol 86:134–137

    Article  PubMed  CAS  Google Scholar 

  15. Yoshimura M, Yasue H, Nakayama M, Shimasaki Y, Sumida H, Sugiyama S, Kugiyama K, Ogawa H, Ogawa Y, Saito Y, Miyamoto Y, Nakao K (1998) A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese. Hum Genet 103:65–69

    Article  PubMed  CAS  Google Scholar 

  16. Rao CV (2004) Nitric oxide signaling in colon cancer chemoprevention. Mutat Res 555:107–119

    Article  PubMed  CAS  Google Scholar 

  17. Metzger IF, Serto′rio JT, Tanus-Santos JE (2007) Modulation of nitric oxide formation by endothelial nitric oxide synthase gene haplotypes. Free Radic Biol Med 43:987–992

    Article  PubMed  CAS  Google Scholar 

  18. Tesauro M, Thompson WC, Rogliani P, Qi L, Chaudhary PP, Moss J (2000) Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate versus glutamate at position 298. Proc Natl Acad Sci USA 97:2832–2835

    Article  PubMed  CAS  Google Scholar 

  19. Persu A, Stoenoiu MS, Messiaen T, Davila S, Robino C, El-Khattabi O, Mourad M, Horie S, Feron O, Balligand JL, Wattiez R, Pirson Y, Chauveau D, Lens XM, Devuyst O (2002) Modifier effect of NOS3 in autosomal dominant polycystic kidney disease. Hum Mol Genet 11:229–241

    Article  PubMed  CAS  Google Scholar 

  20. Miller SA, Dykes DD, Polesky HF (1998) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  Google Scholar 

  21. Miyamoto Y, Saito Y, Kajiyama N, Yoshimura M, Shimasaki Y, Nakayama M, Kamitani S, Harada M, Ishikawa M, Kuwahara K, Ogawa E, Hamanaka I, Takahashi N, Kaneshige T, Teraoka H, Akamizu T, Azuma N, Yoshimasa Y, Yoshimasa T, Itoh H, Masuda I, Yasue H, Nakao K (1998) Endothelial nitric oxide synthase gene is positively associated with essential hypertension. Hypertension 32:3–8

    PubMed  CAS  Google Scholar 

  22. Ying L, Hofseth LJ (2007) Emerging role for endothelial nitric oxide synthase in chronic inflammation and cancer. Cancer Res 67:1407–1410

    Article  PubMed  CAS  Google Scholar 

  23. Lu J, Wei Q, Bondy ML, Yu TK, Li D, Brewster A, Shete S, Sahin A, Meric-Bernstam F, Wang LE (2006) Promoter polymorphism (786t > C) in the endothelial nitric oxide synthase gene is associated with risk of sporadic breast cancer in non-Hispanic white women age younger than 55 years. Cancer 107:2245–2253

    Article  PubMed  CAS  Google Scholar 

  24. Choi JY, Lee KM, Noh DY, Ahn SH, Lee JE, Han W, Jang IJ, Shin SG, Yoo KY, Hayes RB, Kang D (2006) Genetic polymorphisms of eNOS, hormone receptor status, and survival of breast cancer. Breast Cancer Res Treat 100:213–218

    Article  PubMed  CAS  Google Scholar 

  25. Medeiros RM, Morais A, Vasconcelos A, Costa S, Pinto D, Oliveira J, Ferreira P, Lopes C (2002) Outcome in prostate cancer: association with endothelial nitric oxide synthase Glu-Asp298 polymorphism at exon 7. Clin Cancer Res 8:3433–3437

    PubMed  CAS  Google Scholar 

  26. Yang J, Ambrosone CB, Hong C-C, Ahn J, Rodriguez C, Thun MJ, Calle EE (2007) Relationships between polymorphisms in NOS3 and MPO genes, cigarette smoking and risk of post-menopausal breast cancer. Carcinogenesis 28:1247–1253

    Article  PubMed  CAS  Google Scholar 

  27. Sonveaux P, Jordan BF, Gallez B, Feron O (2009) Nitric oxide delivery to cancer: why and how? Eur J Cancer 45:1352–1369

    Article  PubMed  CAS  Google Scholar 

  28. Conde MC, Ramirez-Lorca R, Lopez-Jamar JME, Molero E, Ramirez-Armengol JA, Nogueira JAM, Pascual MH, Ruiz A, Martin-Cordova CG, Real LM, Royo JL (2006) Genetic analysis of caveolin-1 and eNOS genes in colorectal cancer. Oncol Rep 16:353–359

    PubMed  CAS  Google Scholar 

  29. Yeh CC, Santenalla RM, Hsieh LL, Sung FC, Tang R (2009) An intron 4 VNTR polymorphism of the endothelial nitric oxide synthase gene is associated with early-onset colorectal cancer. Int J Cancer 124:1565–1571

    Article  PubMed  CAS  Google Scholar 

  30. Mozet C, Marin DG, Bertolini J, Tannapfel A, Wichmann G, Dietz A (2009) Nitric oxide synthase (NOS2/3) expression in head and neck squamous cell carcinomas in correlation with clinical patterns. Onkologie 32:655–660

    Article  PubMed  CAS  Google Scholar 

  31. Fujita S, Masago K, Hatachi Y, Fukuhara A, Hata A, Kaji R, Kim YH, Mio T, Mishima M, Katakami N (2010) Genetic polymorphisms in the endothelial nitric oxide synthase gene correlate with overall survival in advanced non-small lung cancer patients treated with platinum-based doublet chemotherapy. BMC Med Genet 11:167

    Article  PubMed  CAS  Google Scholar 

  32. Veldman BA, Spiering W, Doevendans PA, Vervoort G, Kron AA, de Leeuw PW, Smits P (2002) The Glu298Asp polymorphism of the NOS3 gene as a determinant of the baseline production of nitric oxide. J.Hypertens 20:2023–2027

    Article  PubMed  CAS  Google Scholar 

  33. Moochhala S, Chhatwal VJ, Chan ST, Ngoi SS, Chia YW, Rauff A (1996) Nitric oxide synthase activity and expression in human colorectal cancer. Carcinogenesis 17:1171–1174

    Article  PubMed  CAS  Google Scholar 

  34. Yu JX, Cui L, Zhang QY, Chen H, Ji P, Wei HJ, Ma HY (2006) Expression of NOS and HIF-1alpha in human colorectal carcinoma and implication in tumor angiogenesis. World J Gastroenterol 12:4660–4664

    PubMed  CAS  Google Scholar 

  35. Mortensen K, Christensen IJ, Nielsen HJ, Hansen U, Larsson LI (2004) High expression of endothelial cell nitric oxide synthase in peritumoral microvessels predicts increased diseasefree survival in colorectal cancer. Cancer Lett 216:109–114

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from Istanbul University, Research Foundation (Project 488/05052006), Turkey. We are also grateful to the cancer epidemiologist Dr. Hakan Camlica for support and correction of statistical analysis.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to İlhan Yaylım-Eraltan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arıkan, S., Cacina, C., Guler, E. et al. The effects of NOS3 Glu298Asp variant on colorectal cancer risk and progression in Turkish population. Mol Biol Rep 39, 3245–3249 (2012). https://doi.org/10.1007/s11033-011-1092-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-1092-8

Keywords

Navigation