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

Abstract

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.

• Authors: Francesco Sclafani, Ian Chau, David Cunningham, Andrea Lampis, Jens Claus Hahne, Michele Ghidini, Hazel Lote, Domenico Zito, Josep Tabernero, Bengt Glimelius, Andres Cervantes, Ruwaida Begum, David Gonzalez De Castro, Sanna Hulkki Wilson, Clare Peckitt, Zakaria Eltahir, Andrew Wotherspoon, Diana Tait, Gina Brown, Jacqueline Oates, Chiara Braconi, Nicola Valeri
• Journal: Carcinogenesis (Carcinogenesis) Vol. 37 Issue 9 Pg. 852-7 (09 2016) ISSN: 1460-2180 [Electronic] England
• PMID: 27381831 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press.

Chemical References

• MIRN608 microRNA, human
• MicroRNAs

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chemoradiotherapy
• Female
• Genotype
• Humans
• Male
• MicroRNAs (genetics)
• Middle Aged
• Neoadjuvant Therapy
• Polymorphism, Single Nucleotide
• Rectal Neoplasms (genetics, mortality, therapy)
• Retrospective Studies