1. Single Nucleotide Polymorphism TGFβ1 R25P Correlates with Acute Toxicity during Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients.
- Author
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Smith JJ, Wasserman I, Milgrom SA, Chow OS, Chen CT, Patil S, Goodman KA, and Garcia-Aguilar J
- Subjects
- Acute Disease, Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Gastrointestinal Diseases epidemiology, Gastrointestinal Diseases genetics, Genetic Markers genetics, Genetic Predisposition to Disease epidemiology, Genetic Predisposition to Disease genetics, Humans, Male, Middle Aged, Neoadjuvant Therapy statistics & numerical data, New York epidemiology, Prevalence, Rectal Neoplasms epidemiology, Retrospective Studies, Risk Factors, Transforming Growth Factor beta1 genetics, Young Adult, Chemoradiotherapy, Adjuvant statistics & numerical data, Polymorphism, Single Nucleotide genetics, Radiation Injuries epidemiology, Radiation Injuries genetics, Rectal Neoplasms genetics, Rectal Neoplasms therapy
- 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 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
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