Glutathıone s-transferaz p1 geni ekson-6 (ala114val) polimorfizminin akciğer kanseri etyolojisındeki olası etkileri [Probable effects of Glutatione S-Transferase P1 gene Exon-6 (Ala114val) polymorphism on the etiology of lung cancer]

Öz

Objectives: Genetic susceptibility also has significant effects on the etiology of lung cancer, besides smoking. Previously it has been reported that some genetic polymorphisms have important roles; especially Glutatyon S-Transferaz P1 (GSTP1) gene for the development of lung cancer. GSTP1 gene has a role in phase II of xenobiotic metabolism. GSTP1 Exon-6 polymorphisms have functional effects on gene production and causes differences in enzyme activity.The aim of this study was to investigate probable effects of GSTP1gene exon-6 (ala114val) polimorphism on the etiology of lung cancer. Materials and methods: Our research population consistsed of 160 subjects; 80 as control group and 80 suffering from lung cancer. Genomic DNA was extracted from peripheral blood leukocytes and the genotypes have been determined by using PCR and RFLP methods. Results: No effect of exon 6 (ala114val) polymorphism genotype of GSTP1 gene were found on etiology of lung cancer in present study. This study showed that smoking, old age and being male are important risk factors for lung cancer. Additionally, our sample\'s GSTP1 gene exon 6 (ala114val) polymorphism genotype frequencies were determined. Conclusions: Our data derived from present study did not suggest an effect of GSTP1gene exon-6 (ala114val) polimorphism on the etiology of lung cancer.

Anahtar Kelimeler

• Polimorphism of GSTP1 - exon-6 (ala114val) - lung cancer -

Glutathione S-transferase P1 geni ekson-6 (ala114val) polimorfizminin akciğer kanseri etyolojisindeki olası etkileri

Öz

Amaç: Akciğer kanseri etiyolojisinde en önemli faktör sigara kullanımı olmakla beraber, genetik faktörlerin de önemli yeri vardır. Genetik etmenlerin rolüne dair yapılan çalışmalarda başta Glutatyon S-Transferaz P1 (GSTP1) geni olmak üzere bazı genetik polimorfizmlerin önemli bir yeri olduğu saptanmıştır. GSTP1 geni, ksenobiyotik metabolizmasının faz II evresinde rol oynamaktadır. GSTP1 ekson-6 polimorfizmleri gen ürünü üzerinde fonksiyonel etkiye sahiptir ve enzim aktivitesinde farklılığa neden olmaktadır. Bu çalışmanın amacı GSTP1geni ekson-6 (ala114val) polimorfizminin akciğer kanseri etyolojisindeki olası etkilerini araştırmaktır. Gereç ve yöntem: Araştırma populasyonumuz; 80 kişi kontrol grubu ve 80 kişi akciğer kanserli olmak üzere toplam 160 kişiden oluşmuştur. Bireylerden alınan kanlardan DNA izolasyonu yapılmış ve genotipler polymerase chain reaction (PCR), ve restriction fragment length polymorphisms (RFLP) yöntemleri kullanılarak belirlenmiştir. Bulgular: GSTP1 geni ekzon 6 (ala114val) polimorfizm bu çalışmada akciğer kanseri etyolojisinde etkili bulunmadı. Bu çalışmada sigara içme, ileri yaş, ve erkek cinsiyet akciğer kanseri için önemli risk faktörleri olarak belirlendi. İlave olarak kendi çalışma grubumuzda GSTP1 geni ekzon 6 (ala114val) polimorfizm sıklığını belirledik. Sonuç: Sonuç olarak, bu çalışmadan elde ettiğimiz verilerle GSTP1 geni ekzon 6 (ala114val) polimorfizmi akciğer kanseri etyolojisinde etkili bulunmadı.

Anahtar Kelimeler

• GSTP1 polimorfizmi, exon-6 (ala114val), akciğer kanseri

Kaynakça

1. Magrath I, Litvak J. Cancer in developing countries: opportu- nity and challenge. J Natl Cancer Inst 1993; 85(11):862-74.
2. Topuz E. Akciğer Kanseri Biyoloji, Tanı, Evreleme ve Te- davi. İstanbul Üniversitesi, Onkoloji Enstitüsü Yayınları, 2001.
3. Radzikowska E, Roszkowski K, Giaz P. Lung cancer in pa- tients under 50 years old. Lung Cancer 2001; 33(2-3):203- 11.
4. Skarin AT, Herbst RS, Leong TL, Bailey A, Sugarbaker D. Lung cancer in patients under age 40. Lung Cancer 2001;32(3):255-64.
5. Garfinkel L, Stellman SD. Smoking and lung cancer in women: findings in a prospective study. Cancer Res1988;48:6951-5.
6. Haugen A, Ryberg D, Mollerup S, Zienolddiny S, Skaug V, Svendsrud DH. Gene-environment interactions in human lung cancer. Toxicol Lett 2000;112(2):233-7.
7. Wu AH, Fontham ET, Reynolds P, et al. Family history of cancer and risk of lung cancer among lifetime non- smoking women in the United States. Am J Epidemiol 1996;143(6):535-42.
8. Sundberg K, Johansson AS, Stenberg G, et al. Differences in the catalytic efficiencies of allelic variants of glutathi- one S transferase P1-1 towards carcinogenic diol epox- ides of polycyclic aromatic hydrocarbons. Carcinogenesis 1998;19(3):433-6.

9. Rahman I, MacNee W. Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway dis- ease. Am J Physiol 1999;277(9):1067-88.
10. Eaton DL, Bammler TK. Concise review of the glutathione S-transferases and their significance to toxicology. Toxicol Sci 1999;49(2):156-64.
11. Ali-Osman F, Akande O, Antoun G, Mao JX, Buolamwi- ni J. Molecular cloning, characterization and expression in Esherichia coli of full-lenght cDNAs of three human glutathione S-transferase pi gene variants. J Biol Chem 1997;272(15):10004-12.
12. Ishii T, Matsuse T, Teramoto S, et al. Glutathione S-trans- ferase P1 (GSTP1) polymorphism in patients with chronic obstructive pulmonary disease. Thorax1999;54(8):693-6.
13. Nazar-Steward V, Vaugan TL, Stapleton P, Van Loo J, Blades NB, Eaton DL. A population-based study of gluta- thione S-transferase M1,T1 and P1 genotypes and risk for lung cancer. Lung Cancer 2003;40(2):247-58.
14. Harries LW, Stubbins MJ, Forman D, Howard CW, Wolf CR. Identification of genetic polymorphisms at the glutathi- one S-transferase Pi locus and association with susceptibili- ty to bladder, testicular and prostate cancer. Carcinogenesis 1997;18(4):641-4.
15. Ryberg D, Skaug V, Hewer A, et al. Genotypes of gluta- thione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis 1997;18(17)1285-9.
16. Wang Y, Spitz MR, Schhabath MB, Ali-Osman F, Mata H, Wu X. Association between glutathione S-transferase P1 polymorphisms and lung cancer risk in Caucasians : a case- control study. Lung Cancer 2003;40(1):25-32.
17. Watson MA, Steward RK, Smith BJ, Massey TE, Bell DA. Human glutathione S-transferase P1 polymorphisms: Re- lationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis 1998;19(2):275-80.
18. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res1988;16(9):1215-20.
19. Vural B, Yakar F, Derin D, et al. Evaluation of Glutathi- one S-Transferase P1 Polymorphisms (Ile105Val and Ala- 114Val) in Patients with Small Cell Lung Cancer. Genet Test Mol Biomarkers 2012; Feb 17. [Epub ahead of print].
20. Saip R, Sen F, Vural B, et al. Glutathione S-transferase P1 polymorphisms are associated with time to tumor progression in small cell lung cancer patients J BUON 2011;16(2):241-6.
21. Booton R, Ward T, Heighway J, Ashcroft L, Morris J, Thatcher N. Glutathione-S-transferase P1 isoenzyme poly- morphisms, platinum-based chemotherapy, and non-small cell lung cancer. J Thorac Oncol 2007; 2(8):734-40.