title: Acute toxicity of radiochemotherapy in rectal cancer patients: a risk particularly for carriers of the TGFB1 Pro25 variant.
abstract: OBJECTIVE
  Transforming growth factor-beta1 is related to adverse events in radiochemotherapy. We investigated TGFB1 genetic variability in relation to quality of life-impairing acute organ toxicity (QAOT) of neoadjuvant radiochemotherapy under clinical trial conditions.
  
  
  METHODS
  Two independent patient cohorts (n = 88 and n = 75) diagnosed with International Union Against Cancer stage II/III rectal cancer received neoadjuvant radiation doses of 50.4 Gy combined with 5-fluorouracil-based chemotherapy. Toxicity was monitored according to Common Terminology Criteria for Adverse Events. QAOT was defined as a CTCAE grade ≥2 for at least one case of enteritis, proctitis, cystitis, or dermatitis. Nine germline polymorphisms covering the common genetic diversity in the TGFB1 gene were genotyped.
  
  
  RESULTS
  In both cohorts, all patients carrying the TGFB1 Pro25 variant experienced QAOT (positive predictive value of 100%, adjusted p = 0.0006). In a multivariate logistic regression model, gender, age, body mass index, type of chemotherapy, or disease state had no significant impact on QAOT.
  
  
  CONCLUSIONS
  The TGFB1 Pro25 variant could be a relevant marker for individual treatment stratification and carriers may benefit from adaptive clinical care or specific radiation techniques.
authors: Department of Clinical Pharmacology, University Medical Center, Göttingen, Germany.
authors: Markus Anton
authors: MA
authors: Schirmer
authors: Caroline Patricia Nadine
authors: CP
authors: Mergler
authors: Margret
authors: M
authors: Rave-Fränk
authors: Markus Karl
authors: MK
authors: Herrmann
authors: Steffen
authors: S
authors: Hennies
authors: Jochen
authors: J
authors: Gaedcke
authors: Lena-Christin
authors: LC
authors: Conradi
authors: Peter
authors: P
authors: Jo
authors: Tim
authors: T
authors: Beissbarth
authors: Clemens Friedrich
authors: CF
authors: Hess
authors: Heinz
authors: H
authors: Becker
authors: Michael
authors: M
authors: Ghadimi
authors: Jürgen
authors: J
authors: Brockmöller
authors: Hans
authors: H
authors: Christiansen
authors: Hendrik Andreas
authors: HA
authors: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods; D015331:Cohort Studies; D003556:Cystitis / Q000473:pathology; D003872:Dermatitis / Q000473:pathology; D004751:Enteritis / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007421:Intestine, Small / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D058958:Organs at Risk / Q000528:radiation effects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011349:Proctitis / Q000473:pathology; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life; D011832:Radiation Injuries / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012044:Regression Analysis; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D001743:Urinary Bladder / Q000528:radiation effects
chemical_list: D009944:Organoplatinum Compounds; D011725:Pyridines; D053773:Transforming Growth Factor beta1; C431073:oxiplatin; D005472:Fluorouracil