DNA repair genes in Sudanese colorectal cancer


Year:

Session type:

Omnia Yousif1, Suleiman Suleiman2, Muntaser Ibrahim1, Omer Elfarog2
1Institute of Endemic Diseases, Khartoum, Sudan, 2Soba University Hospital, Khartoum, Sudan

Background

Colorectal cancer is the 4 th most common type in Sudan. Defects in DNA-repair pathways lead to an accumulation of mutations in genomic DNA that result from non-repair or mis-repair of modifications introduced into the DNA by endogenous or exogenous agents or by the malfunction of DNA metabolic pathways. Until recently, only two repair pathways, postreplicative mismatch repair and nucleotide excision repair, have been linked to cancer in mammals. In addition, the damage-reversal and base-excision-repair processes have been shown to be inactivated in human cancer. The mismatch repair system plays a major role in the processing of recombination intermediates and in the repair of errors made during DNA replication or resulting from chemical damage to DNA. Human homologues of the bacterial and yeast mismatch repair genes have been recently identified, and mutations in these genes have been found to show risk for tumor development in hereditary nonpolyposis colorectal cancer syndrome (HNPCC).

Method

Low density arrays were used to analyze 97 DNA repair pathway genes for 4 familial CRC patients (HNPCC and FAP) and corresponding normal control tissues from the same patient.

Results

Preliminary results show more than 4 fold Lower expression (as compared to controls) of genes like: ERCC1 and APEXL2. High profiles in compared to control were detected in 6 genes: DDB1, ATM, DEPC-1, UBC9, PMS2L3 and GTF2H3. In conclusion the genetic pathways that are involved in the carcinogenesis process of colorectal cancer in Sudan involve different DNA repair pathways and genes.

Conclusion

A new theory that may describe carcinogenes process is provided as a result of this study. Increasing analyzed samples is essential to improve or theory. Correlations between down regulation of DNA repair genes and microsatellite instability (MSI) in the same genes will be conducted.