Increased mRNA expression levels of ERCC1, OGG1 and RAI in colorectal adenomas and carcinomas

Abstract

BACKGROUND: The majority of colorectal cancer (CRC) cases develop through the adenoma-carcinoma pathway. If an increase in DNA repair expression is detected in both early adenomas and carcinomas it may indicate that low repair capacity in the normal mucosa is a risk factor for adenoma formation. METHODS: We have examined mRNA expression of two DNA repair genes, ERCC1 and OGG1 as well as the putative apoptosis controlling gene RAI, in normal tissues and lesions from 36 cases with adenomas (mild/moderat n = 21 and severe n = 15, dysplasia) and 9 with carcinomas. RESULTS: Comparing expression levels of ERCC1, OGG1 and RAI between normal tissue and all lesions combined yielded higher expression levels in lesions, 3.3-fold higher (P = 0.005), 5.6-fold higher (P < 3.10-5) and 7.7-fold higher (P = 0.0005), respectively. The levels of ERCC1, OGG1 and RAI expressions when comparing lesions, did not differ between adenomas and CRC cases, P = 0.836, P = 0.341 and P = 0.909, respectively. When comparing expression levels in normal tissue, the levels for OGG1 and RAI from CRC cases were significantly lower compared to the cases with adenomas, P = 0.012 and P = 0.011, respectively. CONCLUSION: Our results suggest that increased expression of defense genes is an early event in the progression of colorectal adenomas to carcinomas.

I denne delstudien er det sett på to reparasjonsgener, ERCC1 og OGG1 i tillegg til et gen, RAI, som kontrollerer celledød (apoptose). Disse var uttrykt sterkere i adenomer med lett/moderat dysplasi, grov dysplasi og cancer sammenlignet med normalvev. Dette kan tyde på at økt uttrykk av disse forsvarsgenene er noe som skjer tidlig i progresjonen fra adenom til carcinom.