Single nucleotide polymorphisms (SNPs) in microRNA genes have been associated with colorectal cancer (CRC) risk, survival and response to treatment. Conflicting results are available on the association between rs4919510, a SNP in mature miR-608 and clinical outcome in CRC. Here we analysed the association between rs4919510 and benefit from peri-operative treatment in a randomised phase II trial of neoadjuvant Capecitabine and Oxaliplatin (CAPOX) followed by chemo-radiotherapy, surgery and adjuvant CAPOX ± cetuximab in high-risk locally advanced rectal cancer (LARC).A total of 155/164 (94.5%) patients were assessable. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG.Median follow-up was 64.9 months. In the CAPOX arm the 5-yr progression-free survival (PFS) and overall survival (OS) rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12-0.83, p=0.02; HR OS 0.38, 95% CI: 0.14-1.01, p=0.05). In the CAPOX-C arm PFS and OS were 73.2% and 82.2% respectively for CC carriers and 64.6% and 73.1% for CG/GG carriers (HR PFS 1.38, 95% CI: 0.61-3.13, p=0.44; HR OS 1.34, 95% CI: 0.52-3.48, p=0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (p=0.02) and OS (p=0.07).This is the first study investigating rs4919510 in LARC. The CC genotype appeared to be associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy and chemo-radiotherapy alone. Addition of Cetuximab to chemotherapy and chemo-radiotherapy in CC carriers appeared to improve clinical outcome.
- locally advanced rectal cancer