Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients
Sclafani, Francesco (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Chau, Ian (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Cunningham, David (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Lampis, Andrea (The Institute of Cancer Research. Department of Molecular Pathology)
Hahne, Jens Claus (The Institute of Cancer Research. Department of Molecular Pathology)
Ghidini, Michele (The Institute of Cancer Research. Department of Molecular Pathology)
Lote, Hazel (The Institute of Cancer Research. Department of Molecular Pathology)
Zito, Domenico (The Institute of Cancer Research. Department of Molecular Pathology)
Tabernero, Josep (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Glimelius, Bengt (University of Uppsala. Genetics and Pathology, Experimental and Clinical Oncology. Department of Immunology)
Cervantes, Andrés (University of Valencia. Biomedical Research Institute INCLIVA. Department of Haematology and Medical Oncology)
Begum, Ruwaida (The Royal Marsden NHS Foundation Trust. Department of Medicine)
De Castro, David Gonzalez (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Wilson, Sanna Hulkki (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Peckitt, Clare (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Eltahir, Zakaria (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Wotherspoon, Andrew (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Tait, Diana (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Brown, Gina (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Oates, Jacqueline (The Royal Marsden NHS Foundation Trust. Department of Medicine)
Braconi, Chiara (The Institute of Cancer Research. Department of Cancer Therapeutics)
Valeri, Nicola (The Institute of Cancer Research. Department of Molecular Pathology)
Universitat Autònoma de Barcelona

Fecha:	2016
Resumen:	Analysis of a polymorphism in mature microRNA-608 (rs4919510) in rectal cancer patients enrolled in a randomized phase II clinical trial identified patient subpopulations who might benefit from the use of an intensified neo-adjuvant treatment strategy with Cetuximab. 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.
Nota:	Altres ajuts: D.C. received research funding from: Roche, Amgen, Celgene, Sanofi, Merck Serono, Novartis, AstraZeneca, Bayer, Merrimack and MedImmune. C.P. has had advisory roles with Sanofi. J.T. has had advisory roles with Amgen, Roche, Sanofi-Aventis, and Merck. A.C. has had advisory roles with Merck-Serono and Roche. He has received research funding from Roche and honoraria from Roche and Merck-Serono. I.C. has had advisory roles with Merck Serono, Roche, Sanofi Oncology, Bristol Myers Squibb, Eli-Lilly, Novartis, Gilead Science. He has received research funding from Merck-Serono, Novartis, Roche and Sanofi Oncology, and honoraria from Roche, Sanofi-Oncology, Eli-Lilly, Taiho.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Carcinogenesis, Vol. 37 (july 2016) , p. 852-857, ISSN 1460-2180

DOI: 10.1093/carcin/bgw073
PMID: 27381831

6 p, 1.4 MB

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