Pharmacogenetics biomarkers and their specific role in neoadjuvant chemoradiotherapy treatments

An exploratory study on rectal cancer patients

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Article number1482
JournalInternational Journal of Molecular Sciences
Volume17
Issue number9
DOIs
Publication statusPublished - Sep 5 2016

Fingerprint

Chemoradiotherapy
oxaliplatin
Neoadjuvant Therapy
biomarkers
Pharmacogenetics
Biomarkers
Rectal Neoplasms
Radiotherapy Dosage
Radiotherapy
Nucleotides
cancer
Polymorphism
polymorphism
nucleotides
Single Nucleotide Polymorphism
radiation therapy
dosage
Tumors
Genes
minorities

Keywords

  • Chemoradiotherapy
  • Locally advanced rectal cancer
  • Pharmacogenetics

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

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title = "Pharmacogenetics biomarkers and their specific role in neoadjuvant chemoradiotherapy treatments: An exploratory study on rectal cancer patients",
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.",
keywords = "Chemoradiotherapy, Locally advanced rectal cancer, Pharmacogenetics",
author = "Eva Dreussi and Erika Cecchin and Jerry Polesel and Vincenzo Canzonieri and Marco Agostini and Caterina Boso and Claudio Belluco and Angela Buonadonna and Sara Lonardi and Francesca Bergamo and Sara Gagno and {De Mattia}, Elena and Salvatore Pucciarelli and {De Paoli}, Antonino and Giuseppe Toffoli",
year = "2016",
month = "9",
day = "5",
doi = "10.3390/ijms17091482",
language = "English",
volume = "17",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "9",

}

TY - JOUR

T1 - Pharmacogenetics biomarkers and their specific role in neoadjuvant chemoradiotherapy treatments

T2 - An exploratory study on rectal cancer patients

AU - Dreussi, Eva

AU - Cecchin, Erika

AU - Polesel, Jerry

AU - Canzonieri, Vincenzo

AU - Agostini, Marco

AU - Boso, Caterina

AU - Belluco, Claudio

AU - Buonadonna, Angela

AU - Lonardi, Sara

AU - Bergamo, Francesca

AU - Gagno, Sara

AU - De Mattia, Elena

AU - Pucciarelli, Salvatore

AU - De Paoli, Antonino

AU - Toffoli, Giuseppe

PY - 2016/9/5

Y1 - 2016/9/5

N2 - 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.

AB - 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.

KW - Chemoradiotherapy

KW - Locally advanced rectal cancer

KW - Pharmacogenetics

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DO - 10.3390/ijms17091482

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