Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients.
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Date
2016-09-01Author
Sclafani, F
Chau, I
Cunningham, D
Lampis, A
Hahne, JC
Ghidini, M
Lote, H
Zito, D
Tabernero, J
Glimelius, B
Cervantes, A
Begum, R
De Castro, DG
Wilson, SH
Peckitt, C
Eltahir, Z
Wotherspoon, A
Tait, D
Brown, G
Oates, J
Braconi, C
Valeri, N
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Rectal Neoplasms
MicroRNAs
Antineoplastic Combined Chemotherapy Protocols
Neoadjuvant Therapy
Retrospective Studies
Genotype
Polymorphism, Single Nucleotide
Adult
Aged
Middle Aged
Female
Male
Chemoradiotherapy
Research team
Signal Transduction & Molecular Pharmacology
Medicine (RMH Smith Cunningham)
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics
Language
eng
Date accepted
2016-06-28
License start date
2016-09
Citation
Carcinogenesis, 2016, 37 (9), pp. 852 - 857
Publisher
OXFORD UNIV PRESS