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



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.



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).



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.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
J Joshua
JJ
Smith
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.|Icahn School of Medicine at Mount Sinai, New York, New York.
Isaac
I
Wasserman
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Sarah A
SA
Milgrom
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Oliver S
OS
Chow
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Chin-Tung
CT
Chen
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Sujata
S
Patil
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Karyn A
KA
Goodman
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Julio
J
Garcia-Aguilar
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059186:Chemoradiotherapy, Adjuvant / Q000706:statistics & numerical data*; D015331:Cohort Studies; D005260:Female; D005767:Gastrointestinal Diseases / Q000453:epidemiology / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000706:statistics & numerical data; D009518:New York / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011832:Radiation Injuries / Q000453:epidemiology* / Q000235:genetics*; D012004:Rectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D055815:Young Adult
D005819:Genetic Markers; D053773:Transforming Growth Factor beta1