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Int. J. Mol. Sci. 2016, 17(9), 1482; doi:10.3390/ijms17091482

Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

1
Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano 33081, Italy
2
Unit of Cancer Epidemiology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano 33081, Italy
3
Pathology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano 33081, Italy
4
First Surgical Clinic Section, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padova 35128, Italy
5
Nano-Inspired Biomedicine Laboratory, Institute of Pediatric Research-Città della Speranza, Corso Stati Uniti 4, Padova 35127, Italy
6
Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA
7
Radiation Oncology, Istituto Oncologico Veneto—IRCCS, Padova 35128, Italy
8
Surgical Oncology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano 33081, Italy
9
Medical Oncology B, Centro di Riferimento Oncologico, National Cancer Institute, Aviano 33801, Italy
10
Medical Oncology 1, Istituto Oncologico Veneto—IRCCS, Padova 35128, Italy
11
Radiation Oncology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano 33081, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 8 July 2016 / Revised: 11 August 2016 / Accepted: 18 August 2016 / Published: 5 September 2016
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine 2016)
View Full-Text   |   Download PDF [657 KB, uploaded 5 September 2016]   |  

Abstract

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses. View Full-Text
Keywords: pharmacogenetics; locally advanced rectal cancer; chemoradiotherapy pharmacogenetics; locally advanced rectal cancer; chemoradiotherapy
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Dreussi, E.; Cecchin, E.; Polesel, J.; Canzonieri, V.; Agostini, M.; Boso, C.; Belluco, C.; Buonadonna, A.; Lonardi, S.; Bergamo, F.; Gagno, S.; De Mattia, E.; Pucciarelli, S.; De Paoli, A.; Toffoli, G. Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients. Int. J. Mol. Sci. 2016, 17, 1482.

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