Abstract
Purpose :
Oxidative stress (OS) is associated with oxidative DNA damage and is documented to be associated with tumorigenesis. Guanine is most susceptible to OS due to its low oxidation potential. This results in the generation of highly mutagenic oxidative base adduct 8-OHdG (8-hydroxy-2’-deoxyguanosine). 8-OHdG has the ability to pair with adenine and results in G:C→T:A transversions, which result in single and double strand DNA breaks and therefore, an increased mutation rate. Increased plasma levels of 8-OHdG are associated with the development of colorectal carcinoma, ovarian cancer and prostate cancer, but the plasma levels of 8-OHdG have not been evaluated in retinoblastoma patients so far. The present study was undertaken to examine whether plasma 8-OHdG could be a probable factor for the development of unilateral sporadic retinoblastoma.
Methods :
Cases of unilateral sporadic retinoblastoma who presented to our Centre between 2014-2015 were studied. Demographic and clinical features were noted. Blood samples were taken from the patients. DNA isolation, PCR and Sanger’s sequencing was performed to exclude cases with germline mutation in the RB1 gene. 8-OHdG levels were determined in the blood plasma of cases and age matched healthy controls by ELISA (DNA/RNA Oxidative Damage EIA kit from Cayman Chemical, Ann Arbor, MI) and compared between the two groups.
Results :
The study included 36 cases and 36 controls. The mean age of presentation in retinoblastoma children was 22.6±10.8 months. 8-OHdG plasma levels were found to be significantly higher (p value= 0.016) in cases (7579±58 pg/ml) as compared to controls (6179±78 pg/ml).
Conclusions :
This study provides an insight into the possible role of oxidative DNA adduct 8-OHdG in retinoblastoma pathogenesis. Elevated plasma 8-OHdG levels in unilateral sporadic retinoblastoma patients could predispose to somatic mutations in the RB1 gene and may be a probable factor for its development.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.