INVESTIGATION OF THE RELATIONSHIP BETWEEN β2-ADRENERGIC RECEPTOR (β2-AR) POLYMORPHISM AND GASTRİC CANCER

Mustafa Atabey; Ayça Taş; Tuğba Ağbektaş; Meriç Emre Bostancı; Ömer Topcu; Yavuz Siliğ

doi:10.7197/223.vi.431429

EN TR

INVESTIGATION OF THE RELATIONSHIP BETWEEN β2-ADRENERGIC RECEPTOR (β2-AR) POLYMORPHISM AND GASTRİC CANCER

Abstract

Objective: Gastric cancer is a multifunctional disease. Emotional stress, physiological and neuroendocrine changes in cancer patients can lead to the activation of the hypothalamic-pituitary-adrenal axis and the release of hormone dependent hormones such as catecholamine. In particular, it has been reported that catecholamine induction directly affects the biological behavior of tumor cells via β2-Adrenergic receptor (β2-AR) mediated signaling. In this study, it was aimed to investigate polymorphism of β2-AR gene (rs1042717) in gastric cancer patients.

Metods: Polymorphism in the β2-AR gene (rs1042717) was determined by Real-Time PCR method in 60 gastric cancer patients 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 for alcoholic drink consumption (p<0,05). There was a statistically significant relationship between β2-AR (rs1042717) polymorphism and stomach cancer (p <0.05). There was a statistically significant relationship between mutant (AA) genotype with wild type (GG) and heterozygous (AG) polymorphic genotypes when evaluated in β2-AR polymorphism gastric cancer patients and control group (χ2: 19,38, p: 0.001). Similarly, there was a statistically significant correlation between heterozygous (AG) with wild type (GG) and mutant (AA) polymorphic genotypes in gastric cancer (χ2: 14, 27, p: 0,001).

Conclusion: In this study, it was found that the AG genotype is predominant in gastric cancer patients and controls, and that the AA genotype has a protective effect against gastric cancer.

Keywords

β2-adrenergic receptor,gastric cancer,polymorphism,rs1042717

β2-ADRENERJİK RESEPTÖR (β2-AR) POLİMORFİZMİ İLE MİDE KANSERİ ARASINDAKİ İLİŞKİNİN İNCELENMESİ

Öz

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.

Tartışma: Mide kanseri hastaları ve kontroller alkol kullanma açısından değerlendirildiğinde, istatistiksel olarak anlamlı bir ilişki belirlendi (p<0,05). β2-AR (rs1042717) polimorfizmi ile mide kanseri arasında istatistiksel olarak anlamlı bir ilişki bulundu (p<0,05). β2-AR (rs1042717) polimorfizmi mide kanseri hastaları ve kontrol grubunda değerlendirildiğinde, mutant (AA) genotipi ile yabanıl tip (GG) ve heterozigot (AG) polimorfik genotipleri arasında istatistiksel olarak anlamlı bir ilişki olduğu görüldü (χ²: 19,38, p: 0,001). Benzer şekilde heterozigot (AG) ile yabanıl tip (GG) ve mutant (AA) polimorfik genotipleri kıyaslandığında ise mide kanserinde istatistiksel olarak anlamlı bir ilişki olduğu saptandı (χ²: 14,27, p:0,001).

Sonuç: Bu çalışmada, mide kanseri hastaları ve kontrollerde en çok AG genotipinin hakim olduğu ve ayrıca, AA genotipinin mide kanserine karşı koruyucu bir etkiye sahip olduğu görülmüştür.

Anahtar Kelimeler

β2-adrenerjik reseptör,mide kanseri,polimorfizm,rs1042717

Kaynakça

1) 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.
2) Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin 61: 69-90, 2011.
3) Polk, D. B., and R. M. Peek, Jr. 2010. Helicobacter pylori: gastric cancer and beyond. Nat. Rev. Cancer 10: 403–414.
4) 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
5) 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.
6) Johnson M. Beta 2-adrenoceptors: Mechanisms of action of beta 2-agonists. Paediatr. Respir. Rev. 2:57-62;2001
7) 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.
8) 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

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.
10) 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.
11) 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.
12) 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.
13) Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
14) 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
15) 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.
16) Liggett SB. Polymorphisms of the beta2-adrenergic receptor. N Engl J Med. 2002;346:536–8.
17) 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.
18) 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.
19) 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.
20) Shin, J. and Johnson, J.A. (2007) Pharmacogenetics of beta-blockers. Pharmacotherapy, 27, 874-887.
21) 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.
22) Stakos, D.A. and Boudoulas, H. (2002) Pharmacogenetics and pharmacogenomics in cardiology. The Hellenic Jour- nal of Cardiology, 43, 1-15.

Ayrıntılar

Birincil Dil

İngilizce

Konular

Sağlık Kurumları Yönetimi

Bölüm

Araştırma Makalesi

Yazarlar

Mustafa Atabey

Ayça Taş ^*
Türkiye

Tuğba Ağbektaş

Meriç Emre Bostancı

Ömer Topcu

Yavuz Siliğ
Türkiye

Yayımlanma Tarihi

30 Eylül 2018

Gönderilme Tarihi

6 Haziran 2018

Kabul Tarihi

17 Eylül 2018

Yayımlandığı Sayı

Yıl 2018 Cilt: 40 Sayı: 3

DOI

https://doi.org/10.7197/223.vi.431429

IZ

https://izlik.org/JA94TG22GK

Kaynak Göster

RIS / Bibtex

AMA

1.Atabey M, Taş A, Ağbektaş T, Bostancı ME, Topcu Ö, Siliğ Y. INVESTIGATION OF THE RELATIONSHIP BETWEEN β2-ADRENERGIC RECEPTOR (β2-AR) POLYMORPHISM AND GASTRİC CANCER. CMJ. 2018;40(3):284-290. doi:10.7197/223.vi.431429