51. Single Nucleotide Polymorphism TGFβ1 R25P Correlates with Acute Toxicity during Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients
- Author
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Julio Garcia-Aguilar, Chin Tung Chen, Sarah A. Milgrom, Oliver S. Chow, Isaac Wasserman, Sujata Patil, Karyn A. Goodman, and J. Joshua Smith
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,Gastrointestinal Diseases ,Colorectal cancer ,medicine.medical_treatment ,Cohort Studies ,0302 clinical medicine ,Risk Factors ,Prevalence ,Neoadjuvant therapy ,Aged, 80 and over ,education.field_of_study ,Radiation ,Common Terminology Criteria for Adverse Events ,Middle Aged ,Neoadjuvant Therapy ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,Adult ,Genetic Markers ,medicine.medical_specialty ,Population ,New York ,Polymorphism, Single Nucleotide ,Article ,Transforming Growth Factor beta1 ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Radiology, Nuclear Medicine and imaging ,Radiation Injuries ,education ,Aged ,Retrospective Studies ,Rectal Neoplasms ,business.industry ,Retrospective cohort study ,Chemoradiotherapy, Adjuvant ,Odds ratio ,medicine.disease ,Acute toxicity ,Surgery ,030104 developmental biology ,business ,Chemoradiotherapy - 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.
- Published
- 2017
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