title: Predictive role of microRNA-related genetic polymorphisms in the pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients.
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.
authors.affiliation: Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Dreussi
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pucciarelli
authors.affiliation: Radiation Oncology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: De Paoli
authors.affiliation: Epidemiology and Biostatistics, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Jerry
authors.initials: J
authors.lastname: Polesel
authors.affiliation: Pathology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Canzonieri
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy.|Nano Inspired Biomedicine Laboratory, Istituto di Ricerca Pediatrica, Città della Speranza, Padua, Italy.|Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Agostini
authors.affiliation: Radiation Oncology, Istituto Oncologico Veneto, IRCCS, Padova, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Friso
authors.affiliation: Surgical Oncology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Belluco
authors.affiliation: Medical Oncology B, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Buonadonna
authors.affiliation: Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zanusso
authors.affiliation: Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: De Mattia
authors.affiliation: Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
authors.affiliation: Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Cecchin
mesh_terms: D000368:Aged; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D043244:Ribonuclease III / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D035683:MicroRNAs; D051900:Smad3 Protein; C517918:DROSHA protein, human; D043244:Ribonuclease III
keywords: microRNA; neoadjuvant therapy; polymorphisms; rectal cancer