Abstract

DIAGNOSTIC AND PREDICTIVE DNA MARKERS IN SUDANESE PATIENTS WITH COLORECTAL CANCER “THE IMPACT OF ERCC1, XPD, KRAS AND APC GENE’S POLYMORPHISM ON SUDANESE PATIENTS WITH COLORECTAL CANCER

Fariada Babikir A. Badri*, Elsheikh A. Elobeid and Adila Salih El-Obeid

Abstract

Aim: The current study is to examine whether polymorphisms in(ERCC1, ERCC2 (XPD), KRAS, APC) genes have any impact on therisk of colorectal cancer in Sudanese population, also identify their rolein clinical outcome and toxicity profile on patients treated with 5-Flurouracil (FU)/Oxaliplatin for colorectal cancer. Method: In total,50 patients with CRC were recruited, 47 of them received (FOLFOX)treatment as a first- line chemotherapy. Polymorphism in one oncogene(KRAS), one tumor suppressor gene (APC) and two DNA-repairinggenes (ERCC1, ERCC2) were assessed in these patients usingpolymerase chain reaction (PCR), and PCR-restriction fragment lengthpolymorphism (PCR-RFLP) techniques. The correlation between thesepolymorphisms and risk of CRC also with the incidence of oxaliplatintoxicity were evaluated. Result: ERCC1 118, XPD 751 T,C allelesrespectively and mutated KRAS genotypes associated with risk for developing colorectalcancer in Sudanese population with percentages (14%,12%,24%) respectively. Besides nosignificant association between APC I1307K variant and risk of CRC in Sudanesepopulation, but results show a high prevalence of this variant in Sudanese population(patients and healthy individuals) which may predict an ethnic difference. Also our results showed that patients with either ERCC1 118 T/T , XPD 751 C/C ,APC wild genotypes show lower incidence of oxaliplatin toxicity. A stastically siginicant association between the oxaliplatin toxicity and XPD 751 (p= 0.02) and APC I1307K (p=0.01) were identified. Conclusion: Overall, our findings suggest that mutated KRAS, ERCC1 C>T, and XPD A>C have a good impact on CRC risk in Sudanese patients, also mutated KRAS, ERCC1 C>T, XPD A>C and APC I1307K may predict oxaliplatin toxicity in patients treated with oxaliplatin based chemotherapy.

Keywords: ERCC1, ERCC2 (XPD), KRAS, APC, Oxaliplatin.