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Year 2013, Volume: 3 Issue: 5, 0 - , 28.10.2013

CANAN Cacına , SOYKAN Arıkan YEMLİHA Yıldız BAHAR Toptaş SAİME Turan NAZLI Özkan GURBET Korkmaz SEDEN Küçücük ILHAN Yaylım , TURGAY İsbir

Abstract

The role of Nitric Oxide (NO) in tumour biology is not well understood. However, it has been proposed that NO is a highly reactive free radical and plays important roles in growth, progression or metastasis of tumour. Nitric oxide synthases (NOSs) are a family of enzymes that catalyzing the production of (NO) by converting L-arginine to L-citrulline. The aim of present study was to examine Nitric Oxide Synthase 3 (NOS3) Glu298Asp polymorphism in patients with breast cancer. For this purpose, 49 patients with breast cancer and 89 healthy controls were included in the study. The NOS3 Glu298Asp polymorphism were genotyped by PCR-RFLP using peripheral blood samples in our study groups. NOS3 Glu298Asp genotype distribution in the breast cancer patients [GG: 2(4.1%), GT: 22(44.9%), TT: 25(51%)] was statistically different from the healthy control group [GG: 25(28.1%), GT: 34(38.2%), TT: 30(33.7%)] (p=0.024). NOS3 Glu298Asp gene variation T allele frequency was significantly higher in breast cancer patients that of controls (χ2=7.229; p=0.007; OR: 1.228;%95 CI: 1.065-1.415). Conclusion: Our finding suggest that NOS3 Glu298Asp might be associated with breast cancer risk.

Keywords

oxidative stress NOS3 gene variation

References

  • American Cancer Society (2006) Cancer Facts and Figures, 2005. Atlanta, GA,American Cancer Society.
  • MacMahon,B. (2006) Epidemiology and the causes of breast cancer. Int. J. Cancer, 118, 2373–2378.
  • Lancaster J.R. Jr, Xie K. (2006) Tumors face NO problems? Cancer Res., 66, 6459–6462.
  • Arnhold J. (2004) Properties, functions, and secretion of human myeloperoxidase.
  • Biochemistry (Mosc), 69, 4–9. Moncada S, Higgs A. (1993) The L-arginine– nitricoxidepathway.NEnglJMed ,329:2002–12.
  • Lala PK, Orucevic A. (1998) Role of nitric oxide in tumor progression:lessons From experimental tumors.Cancer MetastasisRev, 17:91–106.
  • Choi BM, Pae HO, Jang SI. et al. (2002) Nitric oxide as a pro-apoptotic as well as anti-apoptotic modulator, J Biochem Mol Biol. 35(1):116-26.
  • Ghilardi G, Biondi ML, Cecchini F. et al. (2003)
  • Vascular invasion in human breast cancer is correlated to T786C polymorphism of NOS3 gene. Nitric Oxide 9, 118– 1 Marsden PA, Heng HH, Scherer SW, et al. (1993)
  • Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem., 268:17478–17488.
  • Hao Y., Montiel R., Huang Y. (2010) Endothelial nitric oxide synthase (eNOS) 894 G>T polymorphism is associated with breast cancer risk: a meta-analysis. Breast
  • Cancer Res Treat. Dec;124(3):809-13. doi: 1007/s10549-010-0833-z. Epub 2010 Mar 19.
  • Miller SA, Dykes DD, Polesky HF. (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215
  • McNamara DM, Holubkov R, Postava L. et al. (2003)
  • Effect of the Asp298 Variant of Endothelial Nitric Oxide Synthase on Survival for Patients With Congestive Heart Failure, Circulation, 107;1598-1602.
  • Kelly RA, Balligand JL, Smith TW. (1996) Nitric oxide and cardiac function. Circ Res., 79:363 380.
  • Drexler H. (1999) Nitric oxide synthases in the failing human heart: a double-edged sword? Circulation., 99:2972–2975.
  • Heymes C, Vanderheyden M, Bronzwaer JGF. et al. (1999) Endomyocardial nitric oxide synthase and left ventricular preload reserve in dilated cardiomyopathy. Circulation., 99:3009–3016.
  • Orucevic A., Bechberger J., Green A.M. et al. (1999)
  • Nitric-oxide production by murine mammary adenocarcinoma cells promotes tumour-cell invasiveness, Int. J. Cancer 81, 889–896. K. Mortensen, S. Holck, I.J. Christensen, et al. (1999)
  • Endothelial cell nitric oxide synthase in peritumoral microvessels is a favorable prognostic indicator in premenopausal breast cancer patients, Clin. Cancer Res. 5, 1093–1097.
  • Martin J.H., Begum S., Alalami O. et al. (2000)
  • Endothelial nitric oxide synthase: correlation with histologic grade, lymph node status and estrogen receptor expression in human breast cancer, Tumour Biol. 21, 90– 9 Tesauro M, Thompson WC, Rogliani P, et al. (2000) Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci U S A., 97: 2832–2835.
  • Yang J., Ambrosone CB., Hong CC. et al.(2007) Relationships between polymorphisms in NOS3 and MPO genes, cigarette smoking and risk of post-menopausal breast cancer. Carcinogenesis. 2007 Jun;28(6):1247-53. Epub 2007 Jan 27.
  • Conde M.C., Ramirez-Lorca R., Lopez-Jamar JM. et al. (2006) Genetic analysis of caveolin-1 and eNOS genes in colorectal cancer. Oncol. Rep., 16, 353–359.
  • Medeiros R.M., Morais A., Vasconcelos A. et al. (2002) Outcome in prostate cancer: association with endothelial nitric oxide synthase Glu-Asp298 polymorphism at exon 7. Clin. Cancer Res., 8, 3433–3437.
  • Cheon K.T., Choi K.H., Lee,H.B. et al. (2000) Gene polymorphisms of endothelial Nitric Oxide Synthase and angiotensin-converting enzyme in patients with lung cancer, Lung 178, 351–360.
  • Royo JL., Moreno-Nogueira JA., Galán JJ. et al. (2006) Lack of association between NOS3 Glu298Asp and breast cancer risk: a case-control study. Breast Cancer Res. 100(3):331-3
  • Lu J., Wei Q, Bondy ML. et al. (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
  • Hefler L.A., Grimm C., Lantzsch T. et al. (2006) Polymorphisms of the endothelial nitric oxide synthase gene in breast cancer. Breast Cancer Res. Treat., 98, 151– 15
  • Medeiros R., Morais A., Vasconcelos A. et al. (2002) Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility to prostate cancer. Eur. J. Cancer Prev., 11, 343–350.
  • Riener E.K., Hefler LA., Grimm C. et al. (2004) Polymorphisms of the endothelial nitric oxide synthase gene in women with vulvar cancer. Gynecol. Oncol., 93, 686–690.
  • Choi J.Y. Lee KM., Noh DY. et al. (2006) Genetic polymorphisms of eNOS, hormone receptor status, and survival of breast cancer. Breast Cancer Res. Treat., 100, 213–218. He
  • fler,L.A., Ludwig E., Lampe D., et al. (2002) Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer. Gynecol. Oncol., 86, 134–137.

NİTRİK OKSİT SENTAZ 3 (NOS3) GLU298ASP GEN VARYASYONUNUN MEME KANSERLİ HASTALARDA İNCELENMESİ

Year 2013, Volume: 3 Issue: 5, 0 - , 28.10.2013

CANAN Cacına , SOYKAN Arıkan YEMLİHA Yıldız BAHAR Toptaş SAİME Turan NAZLI Özkan GURBET Korkmaz SEDEN Küçücük ILHAN Yaylım , TURGAY İsbir

Abstract

      Nitrik Oksit'in (NO) tümör biyolojisindeki rolü tam olarak anlaşılamamış olmasına karşın  tümörün büyümesi, gelişmesi ve metastaz gibi durumlarda  önemli rol oynayan bir serbest radikal olduğu ileri sürülmektedir.  Nitrik oksit sentaz (NOS) enzim ailesi L-sitrulinin, L-arginine dönüşümü sırasında Nitrik oksit (NO),  sentezine aracılık eden bir grup katalizörlerdir. Bu çalışmanın amacı Nitrik Oksit Sentaz (NOS3) Glu298Asp polimorfizmini meme kanserli hastalarda araştırmaktır. Bu amaçla 49 meme ve 89 sağlıklı kontrol grubu çalışmaya dahil edilmiştir. Çalışma gruplarımızda NOS3 Glu298Asp polimorfizmi periferal kan örnekleri kullanarak PCR-RFLP yöntemiyle tayin edilmiştir. Meme kanserli hastalarda NOS3 Glu298Asp genotip dağılımı [GG: 2 (4.1%), GT: 22(44.9%), TT: 25(51%)] sağlıklı kontrol grubundan [GG: 25(28.1%), GT: 34(38.2%), TT: 30(33.7%)] istatistiksel olarak anlamlı derecede farklı bulunmuştur (p=0.024). NOS3 Glu298Asp gen varyasyonu T allel frekansı meme kanserli hastalarda kontrol grubuna göre  anlamlı şekilde yüksek olarak saptanmıştır (χ2=7.229; p=0.007; OR: 1.228;%95 CI: 1.065-1.415).

Çalışmamız sonucunda NOS3 Glu298Asp polimorfizminin meme kanseri riski ile ilişkili olabileceği kanısına varılmıştır.

Keywords

oksidatif stres NOS3 geni varyasyon

References

  • American Cancer Society (2006) Cancer Facts and Figures, 2005. Atlanta, GA,American Cancer Society.
  • MacMahon,B. (2006) Epidemiology and the causes of breast cancer. Int. J. Cancer, 118, 2373–2378.
  • Lancaster J.R. Jr, Xie K. (2006) Tumors face NO problems? Cancer Res., 66, 6459–6462.
  • Arnhold J. (2004) Properties, functions, and secretion of human myeloperoxidase.
  • Biochemistry (Mosc), 69, 4–9. Moncada S, Higgs A. (1993) The L-arginine– nitricoxidepathway.NEnglJMed ,329:2002–12.
  • Lala PK, Orucevic A. (1998) Role of nitric oxide in tumor progression:lessons From experimental tumors.Cancer MetastasisRev, 17:91–106.
  • Choi BM, Pae HO, Jang SI. et al. (2002) Nitric oxide as a pro-apoptotic as well as anti-apoptotic modulator, J Biochem Mol Biol. 35(1):116-26.
  • Ghilardi G, Biondi ML, Cecchini F. et al. (2003)
  • Vascular invasion in human breast cancer is correlated to T786C polymorphism of NOS3 gene. Nitric Oxide 9, 118– 1 Marsden PA, Heng HH, Scherer SW, et al. (1993)
  • Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem., 268:17478–17488.
  • Hao Y., Montiel R., Huang Y. (2010) Endothelial nitric oxide synthase (eNOS) 894 G>T polymorphism is associated with breast cancer risk: a meta-analysis. Breast
  • Cancer Res Treat. Dec;124(3):809-13. doi: 1007/s10549-010-0833-z. Epub 2010 Mar 19.
  • Miller SA, Dykes DD, Polesky HF. (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215
  • McNamara DM, Holubkov R, Postava L. et al. (2003)
  • Effect of the Asp298 Variant of Endothelial Nitric Oxide Synthase on Survival for Patients With Congestive Heart Failure, Circulation, 107;1598-1602.
  • Kelly RA, Balligand JL, Smith TW. (1996) Nitric oxide and cardiac function. Circ Res., 79:363 380.
  • Drexler H. (1999) Nitric oxide synthases in the failing human heart: a double-edged sword? Circulation., 99:2972–2975.
  • Heymes C, Vanderheyden M, Bronzwaer JGF. et al. (1999) Endomyocardial nitric oxide synthase and left ventricular preload reserve in dilated cardiomyopathy. Circulation., 99:3009–3016.
  • Orucevic A., Bechberger J., Green A.M. et al. (1999)
  • Nitric-oxide production by murine mammary adenocarcinoma cells promotes tumour-cell invasiveness, Int. J. Cancer 81, 889–896. K. Mortensen, S. Holck, I.J. Christensen, et al. (1999)
  • Endothelial cell nitric oxide synthase in peritumoral microvessels is a favorable prognostic indicator in premenopausal breast cancer patients, Clin. Cancer Res. 5, 1093–1097.
  • Martin J.H., Begum S., Alalami O. et al. (2000)
  • Endothelial nitric oxide synthase: correlation with histologic grade, lymph node status and estrogen receptor expression in human breast cancer, Tumour Biol. 21, 90– 9 Tesauro M, Thompson WC, Rogliani P, et al. (2000) Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci U S A., 97: 2832–2835.
  • Yang J., Ambrosone CB., Hong CC. et al.(2007) Relationships between polymorphisms in NOS3 and MPO genes, cigarette smoking and risk of post-menopausal breast cancer. Carcinogenesis. 2007 Jun;28(6):1247-53. Epub 2007 Jan 27.
  • Conde M.C., Ramirez-Lorca R., Lopez-Jamar JM. et al. (2006) Genetic analysis of caveolin-1 and eNOS genes in colorectal cancer. Oncol. Rep., 16, 353–359.
  • Medeiros R.M., Morais A., Vasconcelos A. et al. (2002) Outcome in prostate cancer: association with endothelial nitric oxide synthase Glu-Asp298 polymorphism at exon 7. Clin. Cancer Res., 8, 3433–3437.
  • Cheon K.T., Choi K.H., Lee,H.B. et al. (2000) Gene polymorphisms of endothelial Nitric Oxide Synthase and angiotensin-converting enzyme in patients with lung cancer, Lung 178, 351–360.
  • Royo JL., Moreno-Nogueira JA., Galán JJ. et al. (2006) Lack of association between NOS3 Glu298Asp and breast cancer risk: a case-control study. Breast Cancer Res. 100(3):331-3
  • Lu J., Wei Q, Bondy ML. et al. (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
  • Hefler L.A., Grimm C., Lantzsch T. et al. (2006) Polymorphisms of the endothelial nitric oxide synthase gene in breast cancer. Breast Cancer Res. Treat., 98, 151– 15
  • Medeiros R., Morais A., Vasconcelos A. et al. (2002) Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility to prostate cancer. Eur. J. Cancer Prev., 11, 343–350.
  • Riener E.K., Hefler LA., Grimm C. et al. (2004) Polymorphisms of the endothelial nitric oxide synthase gene in women with vulvar cancer. Gynecol. Oncol., 93, 686–690.
  • Choi J.Y. Lee KM., Noh DY. et al. (2006) Genetic polymorphisms of eNOS, hormone receptor status, and survival of breast cancer. Breast Cancer Res. Treat., 100, 213–218. He
  • fler,L.A., Ludwig E., Lampe D., et al. (2002) Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer. Gynecol. Oncol., 86, 134–137.
There are 34 citations in total.

Details

Primary Language Turkish
Journal Section Makale
Authors

CANAN Cacına

SOYKAN Arıkan This is me

YEMLİHA Yıldız This is me

BAHAR Toptaş This is me

SAİME Turan This is me

NAZLI Özkan This is me

GURBET Korkmaz This is me

SEDEN Küçücük This is me

ILHAN Yaylım

TURGAY İsbir This is me

Publication Date October 28, 2013
Published in Issue Year 2013 Volume: 3 Issue: 5

Cite

APA Cacına, C., Arıkan, S., Yıldız, Y., Toptaş, B., et al. (2013). NİTRİK OKSİT SENTAZ 3 (NOS3) GLU298ASP GEN VARYASYONUNUN MEME KANSERLİ HASTALARDA İNCELENMESİ. Deneysel Tıp Araştırma Enstitüsü Dergisi, 3(5).
AMA Cacına C, Arıkan S, Yıldız Y, Toptaş B, Turan S, Özkan N, Korkmaz G, Küçücük S, Yaylım I, İsbir T. NİTRİK OKSİT SENTAZ 3 (NOS3) GLU298ASP GEN VARYASYONUNUN MEME KANSERLİ HASTALARDA İNCELENMESİ. Deneysel Tıp Araştırma Enstitüsü Dergisi. July 2013;3(5).
Chicago Cacına, CANAN, SOYKAN Arıkan, YEMLİHA Yıldız, BAHAR Toptaş, SAİME Turan, NAZLI Özkan, GURBET Korkmaz, SEDEN Küçücük, ILHAN Yaylım, and TURGAY İsbir. “NİTRİK OKSİT SENTAZ 3 (NOS3) GLU298ASP GEN VARYASYONUNUN MEME KANSERLİ HASTALARDA İNCELENMESİ”. Deneysel Tıp Araştırma Enstitüsü Dergisi 3, no. 5 (July 2013).
EndNote Cacına C, Arıkan S, Yıldız Y, Toptaş B, Turan S, Özkan N, Korkmaz G, Küçücük S, Yaylım I, İsbir T (July 1, 2013) NİTRİK OKSİT SENTAZ 3 (NOS3) GLU298ASP GEN VARYASYONUNUN MEME KANSERLİ HASTALARDA İNCELENMESİ. Deneysel Tıp Araştırma Enstitüsü Dergisi 3 5
IEEE C. Cacına, “NİTRİK OKSİT SENTAZ 3 (NOS3) GLU298ASP GEN VARYASYONUNUN MEME KANSERLİ HASTALARDA İNCELENMESİ”, Deneysel Tıp Araştırma Enstitüsü Dergisi, vol. 3, no. 5, 2013.
ISNAD Cacına, CANAN et al. “NİTRİK OKSİT SENTAZ 3 (NOS3) GLU298ASP GEN VARYASYONUNUN MEME KANSERLİ HASTALARDA İNCELENMESİ”. Deneysel Tıp Araştırma Enstitüsü Dergisi 3/5 (July 2013).
JAMA Cacına C, Arıkan S, Yıldız Y, Toptaş B, Turan S, Özkan N, Korkmaz G, Küçücük S, Yaylım I, İsbir T. NİTRİK OKSİT SENTAZ 3 (NOS3) GLU298ASP GEN VARYASYONUNUN MEME KANSERLİ HASTALARDA İNCELENMESİ. Deneysel Tıp Araştırma Enstitüsü Dergisi. 2013;3.
MLA Cacına, CANAN et al. “NİTRİK OKSİT SENTAZ 3 (NOS3) GLU298ASP GEN VARYASYONUNUN MEME KANSERLİ HASTALARDA İNCELENMESİ”. Deneysel Tıp Araştırma Enstitüsü Dergisi, vol. 3, no. 5, 2013.
Vancouver Cacına C, Arıkan S, Yıldız Y, Toptaş B, Turan S, Özkan N, Korkmaz G, Küçücük S, Yaylım I, İsbir T. NİTRİK OKSİT SENTAZ 3 (NOS3) GLU298ASP GEN VARYASYONUNUN MEME KANSERLİ HASTALARDA İNCELENMESİ. Deneysel Tıp Araştırma Enstitüsü Dergisi. 2013;3(5).
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