INVESTIGATION OF THE RELATIONSHIP BETWEEN β2-ADRENERGIC RECEPTOR (β2-AR) POLYMORPHISM AND GASTRİC CANCER
Öz
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.
Anahtar Kelimeler
β2-adrenergic receptor gastric cancer polymorphism 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.
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
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 | Cerrahi Tıp Bilimleri Araştırma Yazıları |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Eylül 2018 |
| Kabul Tarihi | 17 Eylül 2018 |
| Yayımlandığı Sayı | Yıl 2018Cilt: 40 Sayı: 3 |