Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients

Sclafani, F. et al. (2016) Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients. Carcinogenesis, 37(9), pp. 852-857. (doi: 10.1093/carcin/bgw073) (PMID:27381831) (PMCID:PMC5008250)

188175.pdf - Published Version
Available under License Creative Commons Attribution.



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 analyzed the association between rs4919510 and benefit from perioperative 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-year 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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Braconi, Dr Chiara and Valeri, Dr Nicola
Authors: Sclafani, F., Chau, I., Cunningham, D., Lampis, A., Hahne, J. C., Ghidini, M., Lote, H., Zito, D., Tabernero, J., Glimelius, B., Cervantes, A., Begum, R., De Castro, D. G., Wilson, S. H., Peckitt, C., Eltahir, Z., Wotherspoon, A., Tait, D., Brown, G., Oates, J., Braconi, C., and Valeri, N.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Carcinogenesis
Publisher:Oxford University Press
ISSN (Online):1460-2180
Published Online:05 July 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Carcinogenesis 37(9): 852-857
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record