Kolorektal kanser riski ile Hipoksiyle İndüklenen Faktör-1alfa (HIF-1α) ve Von Hippel Lindau (VHL) gen polimorfizmleri arasındaki ilişki
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Tarih
2013
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kolorektal kanser insanda sık görülen dört kanser türü arasında yer alır ve ölüme götüren kanserler içerisinde ikinci sıradadır. Kolorektal kanser oluşumunda çevresel ve genetik faktörler etkilidir. Birçok kanser türünün gelişmesinde etkili olduğu düşünülen HIF-1α geni hücrenin hipoksiye cevabının anahtar regülatörüdür. VHL tümör baskılayıcı bir gendir ve hipoksiye cevap yolağında önemli rol alır. Bu çalışmanın amacı, HIF-1α geninin C1772T (rs11549465) ve G1790A (rs11549467) polimorfizmleri ile HIF-1α'nın oksijen-bağımlı degradasyonunu regüle eden VHL genin 5'UTR bölgesindeki fonksiyonel rs779805 polimorfizminin ve ayrıca yaş, cinsiyet, ailede kanser öyküsü, sistemik hastalıklar, beyaz toprak maruziyeti, sigara ve alkol tüketiminin kolorektal kanser riski ile ilişkisini araştırmaktır. Çalışmaya, kolorektal kanser tanısı almış 92 hasta ile kontrol grubu olarak 101 birey alındı. DNA izolasyonu için periferal kan kullanıldı. HIF-1α genindeki rs11549465 C>T ve rs11549467 G>A polimorfizm değişimlerini genotiplemek için ARMS-PZR; VHL rs779805 A>G polimorfizm değişimini genotiplemek için PZR-RFLP moleküler tanı yöntemleri kullanıldı. Hasta ve kontrollerde HIF-1α geni C1772T, G1790A ve VHL geni rs779805 polimorfizmlerinin genetik modellere göre frekansları belirlendi. HIF-1α C1772T polimorfizminin CT/TT genotipleri hasta grubunda daha fazla sayıda bulundu (P<0.05). Odds oranı %95 güven aralığında hesaplandı ve 1.96 (1.02-3.77) olarak bulundu; ancak yaş, cinsiyet, ailede kanser öyküsü, beyaz toprak maruziyetine göre ayarlanmış olan odds oranı (AOR) %95 güven aralığında 4.79 (1.07-21.48) olarak bulundu. Çalışmamızda saptadığımız bu bulgu CT/TT genotiplerine sahip bireylerde kolorektal kanser riskinin artmış olduğunu göstermektedir. Ayrıca ileri yaş, erkek cinsiyet, ailede kanser öyküsü, eşlik eden hastalıklar ve beyaz toprak maruziyetinin kolorektal kanser için birer risk faktörü olduğu istatistiksel analizlerle belirlendi (P<0.05). Hastalarda TNM evrelemesinin genotip dağılımları ile ilişkisine bakıldı, gruplar arsında anlamlı farklılık bulunmadı (P>0.05). Çalışmamızın sonuçları; ileri yaş, erkek cinsiyet, ailede kanser öyküsü, eşlik eden hastalıklar ve beyaz toprak maruziyeti gibi risk faktörlerine ilaveten, HIF-1α C1772T polimorfizmi CT/TT genotip taramasının, kolorektal kanserin erken tanısında avantaj sağlayabilir birer risk belirteci olabileceklerini göstermiştir.
Colorectal cancers are among the four most frequently seen cancers in humans and the 2ndin terms of fatality. Environmental and genetic factors have role in the formation of colorectal cancer. HIF-1α gene, which is thought to have role on development of many cancer types, is the key regulator of cell's response to hypoxia.VHL is a tumor-suppressive gene and has critical role along the pathway of hypoxia response. The aim of this study is to investigate the relation of the C1772T (rs11549465) and G1790A (rs11549467) polymorphisms of HIF-1α gene and the functional rs779805 polymorphism of 5'UTR region of the VHL gene, regulating the oxygen-dependent degradation of HIF-1α, and age, gender, cancer history of family, co-existing diseases, exposure to white soil, consumption of cigarette and alcohol with the risk of colorectal cancer. In the study, 92 patients who have been diagnosed to have colorectal cancer and 101 healthy controls were included. Peripheral blood was used for isolating DNA. ARMS-PZR and PZR-RFLP molecular diagnostic methods were used respectively, to genotype the HIF-1α gene's rs11549465 C>T and rs11549467 G>A, and VHL gene's rs779805 A>G polymorphism transformations. The frequencies of HIF-1α gene's C1772T and G1790A, and VHL gene's rs779805 polymorphisms in patients and controls were determined, according to genetic models. CT/TT genotypes of HIF-1α C1772T polymorphism were found to increase the risk of colorectal cancer in patients (p<0.05). Odds ratio was computed as 1.96 (1.02-3.77) within 95% confidence interval (AOR; Adjusted Odds ratio) was computed as 4.79 (1.07-21.48). This finding in our study shows that colorectal cancer risk increases in patients having CT/TT. Additionally, it was demonstrated via statistical analyses that higher age, male gender, cancer history in family, co-existing diseases, and exposure to white soil stands to be risk factors of colorectal cancer (p<0.05). No significant relation was found between patients' TNM stages and distributions of genotype (p>0.05) The findings from our study demonstrates that, in addition to risk factors for colorectal cancer, of higher age, male gender, cancer story in family, co-existing diseases, and exposure to white soil, scanning CT/TT genotypes of HIF-1α C1772T polymorphism can be advantageous in early-diagnosis of colorectal cancer.
Colorectal cancers are among the four most frequently seen cancers in humans and the 2ndin terms of fatality. Environmental and genetic factors have role in the formation of colorectal cancer. HIF-1α gene, which is thought to have role on development of many cancer types, is the key regulator of cell's response to hypoxia.VHL is a tumor-suppressive gene and has critical role along the pathway of hypoxia response. The aim of this study is to investigate the relation of the C1772T (rs11549465) and G1790A (rs11549467) polymorphisms of HIF-1α gene and the functional rs779805 polymorphism of 5'UTR region of the VHL gene, regulating the oxygen-dependent degradation of HIF-1α, and age, gender, cancer history of family, co-existing diseases, exposure to white soil, consumption of cigarette and alcohol with the risk of colorectal cancer. In the study, 92 patients who have been diagnosed to have colorectal cancer and 101 healthy controls were included. Peripheral blood was used for isolating DNA. ARMS-PZR and PZR-RFLP molecular diagnostic methods were used respectively, to genotype the HIF-1α gene's rs11549465 C>T and rs11549467 G>A, and VHL gene's rs779805 A>G polymorphism transformations. The frequencies of HIF-1α gene's C1772T and G1790A, and VHL gene's rs779805 polymorphisms in patients and controls were determined, according to genetic models. CT/TT genotypes of HIF-1α C1772T polymorphism were found to increase the risk of colorectal cancer in patients (p<0.05). Odds ratio was computed as 1.96 (1.02-3.77) within 95% confidence interval (AOR; Adjusted Odds ratio) was computed as 4.79 (1.07-21.48). This finding in our study shows that colorectal cancer risk increases in patients having CT/TT. Additionally, it was demonstrated via statistical analyses that higher age, male gender, cancer history in family, co-existing diseases, and exposure to white soil stands to be risk factors of colorectal cancer (p<0.05). No significant relation was found between patients' TNM stages and distributions of genotype (p>0.05) The findings from our study demonstrates that, in addition to risk factors for colorectal cancer, of higher age, male gender, cancer story in family, co-existing diseases, and exposure to white soil, scanning CT/TT genotypes of HIF-1α C1772T polymorphism can be advantageous in early-diagnosis of colorectal cancer.
Açıklama
Doktora Tezi
Anahtar Kelimeler
HIF-1α, VHL, Polimorfizm, rs11549465, rs11549467, rs779805, Kolorektal Kanser, Polymorphism, Colorectal Cancer
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Demirel, H. S. (2013). Kolorektal kanser riski ile Hipoksiyle İndüklenen Faktör-1alfa (HIF-1α) ve Von Hippel Lindau (VHL) gen polimorfizmleri arasındaki ilişki. (Yayımlanmamış doktora tezi). Necmettin Erbakan Üniversitesi, Sağlık Bilimleri Enstitüsü Tıbbi Biyoloji Anabilim Dalı, Konya.
