Tuğba AĞBEKTAŞ, Ayça TAŞ, Ömer TOPÇU, Meriç Emre BOSTANCI, Mustafa ATABEY, Yavuz SİLİĞ

β2-Adrenerjik reseptör (β2-ar) polimorfizmi ile mide kanseri arasındaki ilişkinin incelenmesi

Amaç: Mide kanseri multi-fonksiyonel bir hastalıktır. Kanser hastalarında duygusal stres, fizyolojik ve nöroendokrin değişiklikler, hipotalamik-pitüiter-adrenal eksenin aktivasyonuna ve katekolamin gibi strese bağlı hormonların serbest bırakılmasına neden olabilmektedir. Özellikle katekolaminin uyarılması ile β2-Adrenerjik reseptör (β2-AR) aracılı sinyal ileti yoluyla tümör hücrelerinin biyolojik davranışlarını doğrudan etkilediği bildirilmiştir. Bu çalışmada, mide kanserli hastalarda β2-AR gen (rs1042717) polimorfizminin araştırılması amaçlanmıştır. Yöntem: β2-AR genindeki polimorfizim (rs1042717) 60 mide kanseri hastası ve 50 sağlıklı kontrol de Real-Time PCR metoduyla belirlendi. Elde edilen sonuçlar, lojistik regresyon ve Khi-kare (χ2) testi kullanılarak değerlendirildi. Bulgular: Mide kanseri hastaları ve kontroller alkol kullanma açısından değerlendirildiğinde, istatistiksel olarak anlamlı bir ilişki belirlendi (p

Investigation of the relationship between β2- adrenergic receptor (β2-AR) polymorphism and gastric cancer

Objective: Gastric cancer is a multifunctional disease. Emotional stress, physiological and neuroendocrine changes incancer patients can lead to the activation of the hypothalamic-pituitary-adrenal axis and the release of hormonedependent hormones such as catecholamine. In particular, it has been reported that catecholamine induction directlyaffects the biological behavior of tumor cells via β2-Adrenergic receptor (β2-AR) mediated signaling. In this study, itwas aimed to investigate polymorphism of β2-AR gene (rs1042717) in gastric cancer patients.Method: Polymorphism in the β2-AR gene (rs1042717) was determined by Real-Time PCR method in 60 gastric cancerpatients and 50 healthy controls. The results were evaluated using logistic regression and Chi-square (χ2) test.Results: The comparison of gastric cancer patients and controls determined a statistically significant relationship foralcoholic drink consumption (p

PDF

___

Nakao M, Matsuo K, Ito H, Shitara K, Hosono S, Watanabe M, Ito S, Sawaki A, Iida S, Sato S, et al: ABO genotype and the risk of gastric cancer, atrophic gastritis, and Helicobacter pylori infection. Cancer Epidemiol Biomarkers Prev 20: 1665-1672, 2011.
Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin 61: 69-90, 2011.
Polk, D. B., and R. M. Peek, Jr. 2010. Helicobacter pylori: gastric cancer and beyond. Nat. Rev. Cancer 10: 403–414.
Marte B: Cancer: Super p53. Nature 420: 279, 2002. Siegel R.L, Miller K.D, Jemal A. Cancer Statistics, 2017. CA CANCER J CLIN 2017; 67: 7–30
Park, P. G., Merryman, J., Orloff, M., and Schuller, H. M. (1995). Betaadrenergic mitogenic signal transduction in peripheral lung adenocarcinoma: Implications for individuals with preexisting chronic lung disease. Cancer Res. 55, 3504–3508.
Johnson M. Beta 2-adrenoceptors: Mechanisms of action of beta 2-agonists. Paediatr. Respir. Rev. 2:57-62;2001
Strader C.D, Candelore M.R, Hill W.S, Sigal I. S, Dixon R.A. Identification of two serine residues involved in agonist activation of the beta-adrenergic receptor. J.Biol. Chem. 264:13572-13578; 1989.
Kobilka B.K, Dixon R.A, Frielle T, Dolhman H.G, Bolanowski M.A, Sigal I.S, et al. cDNA for the human beta 2-adrenergic receptor: A protein with multiple membrane-spanning domains and encoded by gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. Proc. Natl. Acad. Sci USA 84:46-50;1987
Reihsaus E, Innis M, MacIntyre N, et al. Mutations in the gene encoding for the beta 2- adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Bio 1993;8:334-9.
Silverman, E. K.; Kwiatkowski, D. J.; Sylvia, J. S.; Lazarus, R.; Drazen, J. M. C.; Lange, C.; et al. Family-based association analysis of beta2-adrenergic receptor polymorphisms in the childhood asthma management program. J. Allergy Clin. Immunol. 112:870–876; 2003.
Martinez, J. A.; Corbalan, M. S.; Sanchez- Villegas, A.; Forga, L.; Marti, A.; Martinez- Gonzalez, M. A. Obesity risk is associated with carbohydrate intake in women carrying the Gln27Glu beta2-adrenoceptor polymorphism. J. Nutr. 133:2549–2554; 2003.
Wang, H.; Hao, B.; Chen, X.; Zhao, N.; Cheng, G.; Jiang, Y.; et al. Beta-2 adrenergic receptor gene (ADRB2) poly morphism and risk for lung adenocarcinoma: A case-control study in a Chinese population. Cancer Lett. 240: 297–305; 2006.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
Chiurillo M.A. Role of gene polymorphisms in gastric cancer and its precursor lesions: Current knowledge and perspectives in Latin American countries. World J Gastroenterol 2014 April 28; 20(16): 4503-4515
Ferlay J, Shin HR, Bray F, Mathers C, Parkin DM. Globocan 2008 v1.2, Cancer incidence and mortality worldwide: IARC CancerBase No. 10. International Agency for Research on Cancer. Lyon, France; 2012.
Liggett SB. Polymorphisms of the beta2- adrenergic receptor. N Engl J Med. 2002;346:536–8.
Litonjua AA, Gong L, Duan QL, Shin J, Moore MJ, Weiss ST, et al. Very important pharmacogene summary ADRB2. Pharmacogenet Genomics. 2010;20:64–9.
Reihsaus E, Innis M, MacIntyre N, et al. Mutations in the gene encoding for the beta 2- adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Bio 1993;8: 334-9
Johnson, J.A. and Liggett, S.B. (2011) Cardiovascular pha- rmacogenomics of adrenergic receptor signaling: Clinical implications and future directions. Clinical Pharmaco- logy & Therapeutics, 89, 366-378.
Shin, J. and Johnson, J.A. (2007) Pharmacogenetics of beta-blockers. Pharmacotherapy, 27, 874-887.
Johnson, J.A., Zineh, I., Puckett, B.J., McGorray, S.P., Yarandi, H.N. and Pauly, D.F. (2003) Beta1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clinical Pharmacology & Therapeutics, 74, 44-52.
Stakos, D.A. and Boudoulas, H. (2002) Pharmacogenetics and pharmacogenomics in cardiology. The Hellenic Jour- nal of Cardiology, 43, 1-15.