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Title: Single Nucleotide Polymorphism TGFβ1 R25P Correlates with Acute Toxicity during Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients

Abstract

Purpose: To validate the finding of an association between single nucleotide polymorphisms (SNPs) and toxicity during chemoradiotherapy (CRT) in rectal cancer patients, in an independent population. Methods and Materials: The cohort consisted of 165 patients who received CRT for rectal cancer from 2006 to 2012. Prospectively recorded toxicity information, graded according to the Common Terminology Criteria for Adverse Events version 3.0, was retrieved from the medical record. Additionally, a subset of 52 patients recorded their gastrointestinal symptoms weekly during CRT, using the 7-item Bowel Problems Scale. Deoxyribonucleic acid was extracted from normal tissue in the proctectomy specimens and screened for 3 SNPs: XRCC1 R399Q, XPD K751Q, and TGFβ1 R25P. Univariable and multivariable logistic regression models were constructed. Results: The median radiation dose was 50.4 Gy, and all patients received concurrent chemotherapy. Toxicities measured by the Common Terminology Criteria for Adverse Events were closely associated with patient-reported outcomes for the patients who completed the 7-item Bowel Problems Scale. Grade ≥3 toxicity occurred during CRT in 14 patients (8%). All 14 patients had either XRCC1 R399Q or TGFβ1 R25P polymorphisms. The TGFβ1 R25P polymorphism was significantly associated with grade ≥3 toxicity (odds ratio [OR] 3.47, P=.04) and, in patients who completed the Bowel Problemsmore » Scale, with grade ≥4 toxicity (OR 5.61, P=.02). The latter finding persisted in a multivariable logistic regression model controlling for ethnicity, age, and sex (adjusted OR 1.83, P=.02). Conclusions: We have validated the correlation between the TGFβ1 R25P SNP and acute toxicity during CRT in an independent cohort using both clinician- and patient-reported toxicity. The information from our study could be used as a basis to formulate a prospective trial testing the utility of this SNP as a biomarker of acute toxicity during neoadjuvant treatment in locally advanced rectal cancer.« less

Authors:
 [1];  [1];  [2];  [3]; ;  [1];  [4];  [3];  [1]
  1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York (United States)
  2. (United States)
  3. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)
  4. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States)
Publication Date:
OSTI Identifier:
22649881
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 97; Journal Issue: 5; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BIOLOGICAL MARKERS; CHEMOTHERAPY; COMBINED THERAPY; CORRELATIONS; GY RANGE 10-100; MEDICAL RECORDS; NEOPLASMS; NUCLEOTIDES; PATIENTS; RADIATION DOSES; RADIOTHERAPY; RECTUM; TOXICITY

Citation Formats

Smith, J. Joshua, Wasserman, Isaac, Icahn School of Medicine at Mount Sinai, New York, New York, Milgrom, Sarah A., Chow, Oliver S., Chen, Chin-Tung, Patil, Sujata, Goodman, Karyn A., and Garcia-Aguilar, Julio, E-mail: garciaaj@mskcc.org. Single Nucleotide Polymorphism TGFβ1 R25P Correlates with Acute Toxicity during Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients. United States: N. p., 2017. Web. doi:10.1016/J.IJROBP.2016.12.015.
Smith, J. Joshua, Wasserman, Isaac, Icahn School of Medicine at Mount Sinai, New York, New York, Milgrom, Sarah A., Chow, Oliver S., Chen, Chin-Tung, Patil, Sujata, Goodman, Karyn A., & Garcia-Aguilar, Julio, E-mail: garciaaj@mskcc.org. Single Nucleotide Polymorphism TGFβ1 R25P Correlates with Acute Toxicity during Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients. United States. doi:10.1016/J.IJROBP.2016.12.015.
Smith, J. Joshua, Wasserman, Isaac, Icahn School of Medicine at Mount Sinai, New York, New York, Milgrom, Sarah A., Chow, Oliver S., Chen, Chin-Tung, Patil, Sujata, Goodman, Karyn A., and Garcia-Aguilar, Julio, E-mail: garciaaj@mskcc.org. Sat . "Single Nucleotide Polymorphism TGFβ1 R25P Correlates with Acute Toxicity during Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients". United States. doi:10.1016/J.IJROBP.2016.12.015.
@article{osti_22649881,
title = {Single Nucleotide Polymorphism TGFβ1 R25P Correlates with Acute Toxicity during Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients},
author = {Smith, J. Joshua and Wasserman, Isaac and Icahn School of Medicine at Mount Sinai, New York, New York and Milgrom, Sarah A. and Chow, Oliver S. and Chen, Chin-Tung and Patil, Sujata and Goodman, Karyn A. and Garcia-Aguilar, Julio, E-mail: garciaaj@mskcc.org},
abstractNote = {Purpose: To validate the finding of an association between single nucleotide polymorphisms (SNPs) and toxicity during chemoradiotherapy (CRT) in rectal cancer patients, in an independent population. Methods and Materials: The cohort consisted of 165 patients who received CRT for rectal cancer from 2006 to 2012. Prospectively recorded toxicity information, graded according to the Common Terminology Criteria for Adverse Events version 3.0, was retrieved from the medical record. Additionally, a subset of 52 patients recorded their gastrointestinal symptoms weekly during CRT, using the 7-item Bowel Problems Scale. Deoxyribonucleic acid was extracted from normal tissue in the proctectomy specimens and screened for 3 SNPs: XRCC1 R399Q, XPD K751Q, and TGFβ1 R25P. Univariable and multivariable logistic regression models were constructed. Results: The median radiation dose was 50.4 Gy, and all patients received concurrent chemotherapy. Toxicities measured by the Common Terminology Criteria for Adverse Events were closely associated with patient-reported outcomes for the patients who completed the 7-item Bowel Problems Scale. Grade ≥3 toxicity occurred during CRT in 14 patients (8%). All 14 patients had either XRCC1 R399Q or TGFβ1 R25P polymorphisms. The TGFβ1 R25P polymorphism was significantly associated with grade ≥3 toxicity (odds ratio [OR] 3.47, P=.04) and, in patients who completed the Bowel Problems Scale, with grade ≥4 toxicity (OR 5.61, P=.02). The latter finding persisted in a multivariable logistic regression model controlling for ethnicity, age, and sex (adjusted OR 1.83, P=.02). Conclusions: We have validated the correlation between the TGFβ1 R25P SNP and acute toxicity during CRT in an independent cohort using both clinician- and patient-reported toxicity. The information from our study could be used as a basis to formulate a prospective trial testing the utility of this SNP as a biomarker of acute toxicity during neoadjuvant treatment in locally advanced rectal cancer.},
doi = {10.1016/J.IJROBP.2016.12.015},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 97,
place = {United States},
year = {Sat Apr 01 00:00:00 EDT 2017},
month = {Sat Apr 01 00:00:00 EDT 2017}
}