Publication: Kolorektal kanser tanısı konmuş olgularda ve birinci derece yakınlarında DNA hasarının araştırılması
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2011-01-01
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Amaç: Dünyanın pek çok ülkesinde yapılan araştırmalar kalıtımsal
duyarlılık ve çevresel faktörlerin etkileri sonucu kolorektal kanserlerin
oluştuğuna işaret etmektedir. Kolorektal kanser hastalarının birinci
derece yakınlarında kansere yakalanma riskinin diğer bireylere oranla iki
kat daha yüksek olduğu yapılan çalışmalar ile gösterilmiştir. Kolorektal
kanserin moleküler ve biyolojik özellikleri hakkındaki bilgilerin hızla artması patogenezine ışık tutmaktadır. Artan kanser riskinin belirlenmesi
için biyogöstergelerden sıklıkla yararlanılmaktadır. Bu çalışmanın amacı,
genotoksisite çalışmalarında DNA hasarının gösterilmesinde oldukça
başarılı bir biyogösterge olan comet tekniği ile kolorektal kanser hastaları ve birinci derece yakınlarının lenfositlerindeki muhtemel genotoksik
etkilerin sağlıklı gönüllüler ile karşılaştırılmasıdır.
Yöntemler: Henüz hiç tedavi görmemiş, yeni teşhis edilmiş kolorektal kanser hastalarından (n=26), birinci derece yakınlarından (n=26)
ve kontrol grubundan (n=18) kan örnekleri toplandı. Comet tekniğinde her örnek için incelenen 50 hücrenin (slayt başına) her birinde
kuyruktaki DNA yüzdesi oranlarının ortalaması “mean tail DNA %”
(%DNAT) görüntüleme analiz sistemi kullanılarak hesaplandı. Yapılan
anket değerlendirmelerinde sosyodemografik özellikler ve DNA
hasarını etkileyebilecek faktörler göz önünde bulundurulmuştur.
Bulgular: Kolorektal kanser hastaları ve birinci derece yakın bireylerin periferal kan lenfositlerinde comet tekniği uygulanması sonucunda elde edilen ortalama %DNAT değerleri (sırasıyla 10.45±1.50 ve
9.83±1.39) olarak saptanmış olup, kontrol grubu (8.59±0.76) ile karşılaştırıldığında istatistiksel olarak anlamlı bir farklılık tespit edilmiştir
(sırasıyla p <0.001, p <0.01).
Sonuç: Bu çalışmada elde edilen sonuçlar kolorektal kanser teşhisi
konmuş hastalarda ve özellikle de birinci derece yakınlarında comet
tekniğinin, DNA hasarını belirlemede bir biyogösterge olarak kullanılabileceğini göstermiştir
Objective: Studies in all over the world have reported that genetic susceptibility and environmental factors play an important role in the formation of colorectal cancer. Overall, individuals with incidence of colorectal cancer in the first-degree relatives are about twice as likely to develop colorectal cancer as those without any family history. The rapid increase about the information on molecular and biological characteristics of colorectal cancer has shed light on the pathogenesis of colorectal cancer. Biomarkers are often utilized for the determination of increased risk of cancer. The aim of our study was to investigate the potential DNA damage using by comet assay in peripheral lymphocytes of colorectal cancer patients, their first degree relatives compared with healthy subjects. Methods: Peripheral blood samples were taken from untreated patients diagnosed with colorectal cancer (n=26), their first degree relatives (n=26) and healthy subjects (n=18) were analyzed by comet assay. A total of 50 individual cells were screened per sample (from each slide). The length of the DNA migrated in the comet tail, which is an estimate of DNA damage, was measured with image analysis system. Mean tail %DNA for each cell was calculated as 100-Head %DNA. Each participant was interviewed with a questionnaire which covered a detailed sociodemographic attributes including variables known to induce the comet frequency. Results: The DNA damage was found significantly higher in colorectal cancer patients and their first degree relatives (respectively 10.45±1.50, 9.83±1.40) as compared with the control group (8.59±0.76) (respectively p <0.001, p <0.01). Conclusion: In this study, our results demonstrate that comet assay can be used as a biomarker for detecting DNA damage in patients diagnosed with colorectal cancer and especially in to demonstrate the damage in their first degree relatives.
Objective: Studies in all over the world have reported that genetic susceptibility and environmental factors play an important role in the formation of colorectal cancer. Overall, individuals with incidence of colorectal cancer in the first-degree relatives are about twice as likely to develop colorectal cancer as those without any family history. The rapid increase about the information on molecular and biological characteristics of colorectal cancer has shed light on the pathogenesis of colorectal cancer. Biomarkers are often utilized for the determination of increased risk of cancer. The aim of our study was to investigate the potential DNA damage using by comet assay in peripheral lymphocytes of colorectal cancer patients, their first degree relatives compared with healthy subjects. Methods: Peripheral blood samples were taken from untreated patients diagnosed with colorectal cancer (n=26), their first degree relatives (n=26) and healthy subjects (n=18) were analyzed by comet assay. A total of 50 individual cells were screened per sample (from each slide). The length of the DNA migrated in the comet tail, which is an estimate of DNA damage, was measured with image analysis system. Mean tail %DNA for each cell was calculated as 100-Head %DNA. Each participant was interviewed with a questionnaire which covered a detailed sociodemographic attributes including variables known to induce the comet frequency. Results: The DNA damage was found significantly higher in colorectal cancer patients and their first degree relatives (respectively 10.45±1.50, 9.83±1.40) as compared with the control group (8.59±0.76) (respectively p <0.001, p <0.01). Conclusion: In this study, our results demonstrate that comet assay can be used as a biomarker for detecting DNA damage in patients diagnosed with colorectal cancer and especially in to demonstrate the damage in their first degree relatives.
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Keywords
DNA hasarı, kolorektal kanser, comet tekniği, DNA damage, colorectal cancer, comet assay
Citation
BECEREN A., OMURTAG G. Z., YEĞEN C., ŞARDAŞ S., "Kolorektal kanser tanısı konmuş olgularda ve birinci derece yakınlarında DNA hasarının araştırılması.", Journal of Marmara University Institute of Health Sciences (MÜSBED), cilt.1, sa.3, ss.155-161, 2011