Kolo-rektal kanserli hasta ve yakınlarında genetik yatkınlığın araştırılması
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Date
1998
Authors
Tunca, Berrin
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Frajil bölgeler kromozomlar üzerinde boya almayan özel gap ve kırık noktalandır ve onlar çeşitli kültür koşullan ile oluşturulabilirler. Çeşitli çalışmalar frajil bölge ekspresyonunu arttıran ve birçok klastojenik ajan olduğunu göstermiştir. Biz de çalışmamızda periferik kan lenfositlerinde gözlediğimiz prometafaz kromozomlarda common frajil bölgelerin ekspresyonunu afidikolin, bromodeoksiuridin ve kafein ile indükledik. Kromozomal aberasyonlar ve frajil bölge ekspresyonlan, 32 kolon kanserli hasta, 30 asemptomatik kolon akraba, 36 rektum kanserli hasta, 30 rektum akraba ve 30 da yaşlan hasta ve akraba grupları ile uyumlu, ailesinde kanser hikayesi bulunmayan sağlıklı kontrol bireylerinden oluşan toplam 158 vakada değerlendirildi. Hem hasarlı hücre oram (P<0.001) hem de hücre basma düşen gap ve kırıkların ortalamaları (P<0.001) kontrol grubu ile karşılaştırıldığında gerek hasta gruplarında gerekse akrabalarda anlamlı bir şekilde yüksek bulundu. Buna karşılık kanserli hastaların gruplan akrabaların olduğu gruplarla karşılaştırıldıklarında anlamlılık elde edilemedi (P>0.05). Biz iki grubumuzda da apbidicolin tip common frajil bölgeler belirledik. Kolon kanserli hastalar ve yakınlarında belirlediğimiz frajil bölgeler lp36, lp31, lp21, lq21, lq25, lq44, 2p24, 2pl6, 2q21, 2q33, 2q37, 3p21, 3pl4, 15ql5, 5q21, 5q31, 13ql3 ve 14q24 şeklinde sıralanmaktadır. Bunlarm içinde lp21, lq21, lq25, lq44, 2p24, 2pl6, 2q33, 2q37, 3pl4, 5q21, 5q31 ve 14q24 frajil bölge oranları, kontrol grubu ile karşılaştırıldığında istatistiki olarak anlamlı bulundu (P<0.05-P<0.0005). Aynca bütün frajil bölgeler içinde en yüksek istatistiki anlamlılığı gösteren bölgeler 2q33, 3pl4 ve 5q21 olarak belirlendi. Rektum kanserli hastalarımız ve akrabalarında 1Ip36, lp31, lp21, lq21, lq25, lq44, 2p24, 2q21, 2q33, 2q37, 3pl4, 5q21, 5q31, 13ql3, 14q24, 16q23 ve 18q21'de frajil bölgeleri saptandı. Bu bölgelerdeki ekspresyon sıklıklan kontrol grubu ile karşılaşünldığmda lp21, lq25, lq44, 2q33, 5q21, 5q31 ve 14q24'de istatistiki anlamlılık belirlendi (P<0.05-P<0.0005). Aynca 2q33 bölgesi rektum kanserli hastalar ve akrabalarında en yüksek anlamlılığa sahip olan frajil bölge idi. Bizim sonuçlarımız kolorektal kanserli hasta ve yakınlarında kromozomal aberasyonlar ve frajil bölge ekspresyonlannda bir artış olduğunu göstermektedir. Bu veriler bize common frajil bölgelerin kırılmada öncelikli noktalar olarak ekspresyonlan ile somatik genomdaki kromozomal hasarın primer sebebi olabileceğini göstermektedir. Böylece bu tip çalışmaların gerçekleştirilmesi kanserin erken tanısında, kanser oluşumundaki biyolojik mekanizmaların açıklanmasında ve kanserden korunmada yardımcı olabilir.
Fragile sites are non-staining gaps and breaks in specific points of chromosomes which are inducible by various culture conditions. Previous studies have shown that various clastogenic agents increase the expression of fragile sites. In this study the expression of common fragile sites induced by aphidicolin, bromodeoxyuridine and caffeine was evaluated on prometaphase chromosomes obtained from the peripheral blood lymphocytes. Chromosomal aberrations and fragile site expression of 158 individuals, including 32 patients with colon cancer, 30 their clinically healty family member, 36 rectum cancered patients, 30 relatives of patients with rectum cancer and 30 age-matched normal healty controls without history about any cancer type were studied. Both the proportion of damaged cells (PO.001) and the mean number of gaps and breaks per cell (PO.001) were significantly higher in the both patient groups and relatives when compared with control group. However, they were insignificant when the patients with cancer were compared to their relatives (P>0.05). We determined aphidicolin type common fragile sites in our both groups. These sites in patients with colon cancer and relatives were following : lp36, lp31, lp21, lq21, lq25, lq44, 2p24, 2pl6, 2q21, 2q33, 2q37, 3p21, 3pl4, 5ql5, 5q21, 5q31, 13ql3 and 14q24, In this fragile sites, lp21, lq21, lq25, lq44, 2p24, 2pl6, 2q33, 2q37, 3pl4, 5q21, 5q31 and 14q24sites were statistically significant when compared with control group (P<0.05-P<0.0001). Moreover expression of 2q33, 3pl4 and 5q21 sites were observed highest significant in all of fragile sites. Fragile sites in rectum cancered patients and their relatives were following: lp36,. Ip31, lp21, lq21, lq25, lq44, 2p24, 2q21, 2q33, 2q37, 3pl4, 5q21, 5q31, 13ql3, 14q24, 16q23 and 18q21. When compared with control group fragile sites of lp21, lq25, lq44, 2q33, 5q21, 5q31 and 14q24 were statistically significant (P<0.05-P<0.0005). Highest statistically significancy was observed in 2q33 in this group. Our results indicate that there is a relative increase in chromosomal aberrations and fragile sites expressions in patients with colorectal cancer and their relatives. These data also suggest that common fragile sites may really be preferential points of breakage and that then- expression might be primary Contibutors to chromosomal damages of the somatic genome. So this type studies may be helpful to early detection of cancer, clarifiy the biological mechanism of cancer development, progression and in the protection from cancer.
Fragile sites are non-staining gaps and breaks in specific points of chromosomes which are inducible by various culture conditions. Previous studies have shown that various clastogenic agents increase the expression of fragile sites. In this study the expression of common fragile sites induced by aphidicolin, bromodeoxyuridine and caffeine was evaluated on prometaphase chromosomes obtained from the peripheral blood lymphocytes. Chromosomal aberrations and fragile site expression of 158 individuals, including 32 patients with colon cancer, 30 their clinically healty family member, 36 rectum cancered patients, 30 relatives of patients with rectum cancer and 30 age-matched normal healty controls without history about any cancer type were studied. Both the proportion of damaged cells (PO.001) and the mean number of gaps and breaks per cell (PO.001) were significantly higher in the both patient groups and relatives when compared with control group. However, they were insignificant when the patients with cancer were compared to their relatives (P>0.05). We determined aphidicolin type common fragile sites in our both groups. These sites in patients with colon cancer and relatives were following : lp36, lp31, lp21, lq21, lq25, lq44, 2p24, 2pl6, 2q21, 2q33, 2q37, 3p21, 3pl4, 5ql5, 5q21, 5q31, 13ql3 and 14q24, In this fragile sites, lp21, lq21, lq25, lq44, 2p24, 2pl6, 2q33, 2q37, 3pl4, 5q21, 5q31 and 14q24sites were statistically significant when compared with control group (P<0.05-P<0.0001). Moreover expression of 2q33, 3pl4 and 5q21 sites were observed highest significant in all of fragile sites. Fragile sites in rectum cancered patients and their relatives were following: lp36,. Ip31, lp21, lq21, lq25, lq44, 2p24, 2q21, 2q33, 2q37, 3pl4, 5q21, 5q31, 13ql3, 14q24, 16q23 and 18q21. When compared with control group fragile sites of lp21, lq25, lq44, 2q33, 5q21, 5q31 and 14q24 were statistically significant (P<0.05-P<0.0005). Highest statistically significancy was observed in 2q33 in this group. Our results indicate that there is a relative increase in chromosomal aberrations and fragile sites expressions in patients with colorectal cancer and their relatives. These data also suggest that common fragile sites may really be preferential points of breakage and that then- expression might be primary Contibutors to chromosomal damages of the somatic genome. So this type studies may be helpful to early detection of cancer, clarifiy the biological mechanism of cancer development, progression and in the protection from cancer.
Description
Keywords
Kolorektal kanser, Frajil bölge, Genetik yatkınlık, Colorectal cancer, Fragile site, Genetic predisposition
Citation
Tunca, B. (1998). Kolo-rektal kanserli hasta ve yakınlarında genetik yatkınlığın araştırılması. Yayınlanmamış doktora tezi. Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.