Predictive role of microRNA-related genetic polymorphisms in the pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients

Eva Dreussi, Salvatore Pucciarelli, Antonino De Paoli, Jerry Polesel, Vincenzo Canzonieri, Marco Agostini, Maria Luisa Friso, Claudio Belluco, Angela Buonadonna, Sara Lonardi, Chiara Zanusso, Elena De Mattia, Giuseppe Toffoli, Erika Cecchin

Research output: Contribution to journalArticle

Abstract

In rectal cancer, a pathologic complete response (pCR) to pre-operative treatment is a favourable prognostic marker, but is reported in a minority of the patients. We aimed at identifying microRNA-related host genetic polymorphisms predictive of pCR. A panel of 114 microRNA-related tagging polymorphisms was selected and analyzed on 265 locally advanced rectal cancer patients treated with neoadjuvant chemo-radiotherapy. Patients were stratified in two subgroups according to the radiotherapy dose (50.4Gy for 202 patients, 55.0Gy for 78 patients). Interactions among genetic and clinical-pathological variants were investigated by recursive partitioning analysis. Only polymorphisms with a consistent significant effect in the two subgroups of patients were selected as predictive markers of pCR. The results were validated by bootstrap analysis. SMAD3-rs744910, SMAD3-rs745103, and TRBP-rs6088619 were associated to an increased chance of pCR (p=0.0153, p=0.0471, p=0.0125). DROSHA-rs10719 and SMAD3-rs17228212 had an opposite detrimental effect on pathological tumour response (p=0.0274, p=0.0049). Recursive partitioning analysis highlighted that a longer interval time between the end of radiotherapy and surgery increases the chance of pCR in patients with a specific combination of SMAD3-rs744910 and TRBP-rs6088619 genotypes. This study demonstrated that microRNA-related host genetic polymorphisms can predict pCR to neo-adjuvant chemo-radiotherapy, and could be used to personalize the interval time between the end of radiotherapy and surgery.

Original languageEnglish
Pages (from-to)19781-19793
Number of pages13
JournalOncotarget
Volume7
Issue number15
DOIs
Publication statusPublished - Apr 12 2016

Keywords

  • MicroRNA
  • Neoadjuvant therapy
  • Polymorphisms
  • Rectal cancer

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Predictive role of microRNA-related genetic polymorphisms in the pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients'. Together they form a unique fingerprint.

  • Cite this