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  • Sclafani, FrancescoRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)

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

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-07-05
  • Oxford University Press (OUP),2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-307293
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-307293URI
  • https://doi.org/10.1093/carcin/bgw073DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

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  • Chau, IanRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • Cunningham, DavidRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • Lampis, AndreaInst Canc Res, Dept Mol Pathol, Sutton SM2 5NG, Surrey, England. (author)
  • Hahne, Jens ClausInst Canc Res, Dept Mol Pathol, Sutton SM2 5NG, Surrey, England. (author)
  • Ghidini, MicheleInst Canc Res, Dept Mol Pathol, Sutton SM2 5NG, Surrey, England. (author)
  • Lote, HazelRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England.;Inst Canc Res, Dept Mol Pathol, Sutton SM2 5NG, Surrey, England. (author)
  • Zito, DomenicoInst Canc Res, Dept Mol Pathol, Sutton SM2 5NG, Surrey, England. (author)
  • Tabernero, JosepUniv Autonoma Barcelona, Vall Hebron Univ Hosp, Dept Med Oncol, Barcelona 08035, Spain. (author)
  • Glimelius, BengtUppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)bengglim (author)
  • Cervantes, AndresUniv Valencia, Biomed Res Inst INCLIVA, Dept Haematol & Med Oncol, Valencia 46010, Spain. (author)
  • Begum, RuwaidaRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • De Castro, David GonzalezRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • Wilson, Sanna HulkkiRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • Peckitt, ClareRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • Eltahir, ZakariaRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • Wotherspoon, AndrewRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • Tait, DianaRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • Brown, GinaRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • Oates, JacquelineRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England. (author)
  • Braconi, ChiaraRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England.;Inst Canc Res, Dept Canc Therapeut, Sutton SM2 5NG, Surrey, England. (author)
  • Valeri, NicolaRoyal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England.;Inst Canc Res, Dept Mol Pathol, Sutton SM2 5NG, Surrey, England. (author)
  • Royal Marsden NHS Fdn Trust, Dept Med, Sutton SM2 5PT, Surrey, England.Inst Canc Res, Dept Mol Pathol, Sutton SM2 5NG, Surrey, England. (creator_code:org_t)

Related titles

  • In:Carcinogenesis: Oxford University Press (OUP)37:9, s. 852-8570143-33341460-2180

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