Kolorektal kanserli hastalarda sitokrom p450 (CYP2C9 ve CYP2C19) enzim genetik polimorfizmi
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Dosyalar
Tarih
2007
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Selçuk Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kolorektal Kanserli Hastalarda Sitokrom P450 (CYP2C9 ve CYP2C19) Enzim Genetik Polimorfizm kolorektalrektal kanserin multifaktöriyel bir hastalık olduğu bilinmektedir. Maruz kalınan çevresel kanserojenler veya endojen kaynaklı bileşikler ile bireyin genetik yapısının etkileşimi sonucu kompleks bir yolla hastalık için risk oluşmaktadır. Bu ilişkiyi aydınlatmak için çeşitli araştırmalar yapılmaktadır.Çalışmamızda, endojen ve ekzojen kaynaklı bileşiklerin modifikasyonunda özellikle de ilaç metabolizmasında önemli roller alan Sitokrom P450 enzim sistemlerini kodlayan gen ailelerinden CYP2C9 ve CYP2C19 alt ailelerinin polimorfik yapıları 85 kolorektal kanserli hasta ve 100 sağlıklı kontrolde araştırıldı. CYP2C9*2, CYP2C9*3 ve CYP2C19*2, CYP2C9*3 genlerinin her birinde tek baz değişiklikleriyle normal allellerden farklılaşan heterozigot ve mutant alleller Real Time Polimeraz Zincir Reaksiyonu yöntemiyle çalışıldı. Veriler hasta-kontrol grubu istatistik sonuçları ve odds oranları incelenerek değerlendirildi. Ayrıca hasta ve kontrol gruplarına uygulanan hasta formunda sigara-alkol alışkanlıkları, kanserli akrabalarının varlığı, kolorektal kansere eşlik eden hastalıkları ve beyaz toprağa maruziyetleri sorgulandı. Sonuçta; polimorfik bir yapıya sahip olan CYP2C9 ve CYP2C19 genlerinin allel sıklığı kolorektal kanser hastalarında ve sağlıklı kontrollerde karşılaştırıldığında aralarında istatistiksel olarak anlamlı bir farklılık bulunmadı (p>0.05). Bulgularımız incelenen heterozigot ve mutant allelerden hiçbirinin kolorektal kanser için risk faktörü olmadığını ortaya koydu. Ancak kolorektal kanserli hastalarda beyaz toprağa maruz kalanların oranı sağlıklı kontrollerden anlamlı oranda (p<0.05) yüksek bulundu ve beyaz toprağın kolorektal kanser için bir risk faktörü olabileceği düşünüldü.
Gene Polimorphism in The Cytochrome P450 (CYP2C9 and CYP2C19) Enzymes in Patients with Colorectal CarsinomaColorectal carsinoma is considered to be a multifactorial disease, in which multiple exposures to endogenous factors and environmental carcinogens interact with individual genetic background in a complex manner resulting in modulation of the risk. There are kindly researches which examined especially relation with the colorectal carsinoma and Cytochrome P450.In this case-control study; we researched the gene polimorphisms of CYP2C9 and CYP2C19, which are the members of CYP 450 super family, playing important roles in metabolisms of endogenous and exogenous compounds and also drugs, in 85 patients with colorectal carcinoma and 100 unrelated, healthy volunteers. Heterozygote and mutant allels of CYP2C9*2, CYP2C9*3 and CYP2C19*2, CYP2C9*3 gene allels which is differ from each other with a single base substitutions; called heterozygote type and mutant type, determinated by Real Time Polymerase Chain Reaction. Results were compared in this case-control subjects statistically and calculated odds ratios were used. Alcohol consumption, smoky habbits, presence of multisystemic diseases, carcinoma history in their families and exposure to asbestos were determined in both control and patients groups. As a result; we compared the polymorphic allel frequencies of CYP2C9 and CYP2C19 genes between patients with colorectal carsinoma and control groups, there were no significant differences among the groups (p>0.05).None of the heterozygote and mutant allels which we studied was a risk factor for colorectal carcinoma. But exposed asbestos ratio in the patients with colorectal carsinoma was significantly higher (p<0.05) then control subjects in our patients, so exposed asbestos may be a risk factor for colorectal carcinoma.
Gene Polimorphism in The Cytochrome P450 (CYP2C9 and CYP2C19) Enzymes in Patients with Colorectal CarsinomaColorectal carsinoma is considered to be a multifactorial disease, in which multiple exposures to endogenous factors and environmental carcinogens interact with individual genetic background in a complex manner resulting in modulation of the risk. There are kindly researches which examined especially relation with the colorectal carsinoma and Cytochrome P450.In this case-control study; we researched the gene polimorphisms of CYP2C9 and CYP2C19, which are the members of CYP 450 super family, playing important roles in metabolisms of endogenous and exogenous compounds and also drugs, in 85 patients with colorectal carcinoma and 100 unrelated, healthy volunteers. Heterozygote and mutant allels of CYP2C9*2, CYP2C9*3 and CYP2C19*2, CYP2C9*3 gene allels which is differ from each other with a single base substitutions; called heterozygote type and mutant type, determinated by Real Time Polymerase Chain Reaction. Results were compared in this case-control subjects statistically and calculated odds ratios were used. Alcohol consumption, smoky habbits, presence of multisystemic diseases, carcinoma history in their families and exposure to asbestos were determined in both control and patients groups. As a result; we compared the polymorphic allel frequencies of CYP2C9 and CYP2C19 genes between patients with colorectal carsinoma and control groups, there were no significant differences among the groups (p>0.05).None of the heterozygote and mutant allels which we studied was a risk factor for colorectal carcinoma. But exposed asbestos ratio in the patients with colorectal carsinoma was significantly higher (p<0.05) then control subjects in our patients, so exposed asbestos may be a risk factor for colorectal carcinoma.
Açıklama
Anahtar Kelimeler
Neoplazmlar, Neoplasms, Genetic polymorphism, Sitokrom P 450, Cytochrome P 450, Genetik polimorfizm
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Büyükdoğan, M. (2007). Kolorektal kanserli hastalarda sitokrom p450 (CYP2C9 ve CYP2C19) enzim genetik polimorfizmi. Selçuk Üniversitesi, Yayımlanmış doktora tezi, Konya.
