BACR 1: Investigating a novel ERCC5 polymorphism as a biomarker of oxaliplatin effect in patients with metastatic colorectal cancer

Joanna Wood1,Jennifer Bowdrey1,Joanna Somers1,Anne Willis1,Anne Thomas1

1University of Leicester, Leicester, UK

Presenting date: Monday 2 November
Presenting time: 12.20-13.10

Background

Expression of DNA repair genes may predict the effects of chemotherapy. This has been illustrated by the observation that patients with low ERCC1 expression, and thus slow repairers of drug induced damage, respond better to platinum-based regimens than the high ERCC1 group.

ERCC5 (XPG) is a nucleotide excision repair (NER) gene involved in 3’cleavage of the damaged area. Our collaborators have identified a SNP in the 5’ untranslated area of this gene that is associated with reduced protein expression and thus presumed diminished DNA repair.  Preclinical and early clinical work has demonstrated that DNA repair is more efficient in the presence of the A than the G SNP. We investigated whether this SNP may be a predictive biomarker of response or toxicities to oxaliplatin containing chemotherapy in patients with metastatic colorectal cancer (mCRC).

Method

Patients with mCRC who had received oxaliplatin chemotherapy were requested to donate a single blood sample for research. DNA was extracted and then sequenced for this SNP in the ERCC5 gene.

Results

47 patients were recruited, 43 of whom had received FOLFOX and 4 had received CapeOx (+ / - targeted treatments). The SNP was assessed in all participants (31 GG, 14 AG and 2 AA). There was no association of genotype with response to treatment. Severe (grade 3 or 4) toxicities occurred in 13 (27%) of participants, neuropathy being the most common. There was a trend that GG homozygotes had a higher rate of toxicities than those with 1 or 2 A alleles (55% versus 14% P = 0.0974 Fisher test).

Conclusion

These data imply that the presence of at least 1 A allele, in this SNP allows for enhanced DNA repair, and thus may protect against side-effects of oxaliplatin chemotherapy.