Single nucleotide polymorphism TGFβ1 R25P correlates with acute toxicity during neoadjuvant chemoradiotherapy in rectal cancer patients

Publication date: Available online 18 December 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): J. Joshua Smith, Isaac Wasserman, Sarah A. Milgrom, Oliver S. Chow, Chin-Tung Chen, Sujata Patil, Karyn A. Goodman, Julio Garcia-Aguilar
Purpose/Objective: Our group and others have identified an association between single nucleotide polymorphisms (SNPs) and toxicity during chemoradiotherapy (CRT) in rectal cancer patients. This study aimed to validate these findings in an independent population.Methods and MaterialsThe 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 (CTCAE) 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. DNA 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.ResultsThe median radiation dose was 50.4 Gy, and all patients received concurrent chemotherapy. Toxicities measured by CTCAE were closely associated with patients 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 (OR 3.47, p = 0.04) and, in patients who completed the Bowel Problems Scale, with grade ≥4 toxicity (OR 5.61, p = 0.02). The latter finding persisted in a multivariable logistic regression model controlling for ethnicity, age, and gender (adjusted OR 1.83, p = 0.02).ConclusionsWe 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 its utility as a biomarker of acute toxicity during neoadjuvant treatment in locally advanced rectal cancer.

Teaser

Our group and others have identified an association between single nucleotide polymorphisms and acute toxicity in patients receiving neoadjuvant chemoradiotherapy for rectal cancer. The current study validated these correlations in an independent cohort of 165 patients.


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