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Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):149-57. doi: 10.1016/j.ijrobp.2011.05.063. Epub 2011 Oct 12.

Acute toxicity of radiochemotherapy in rectal cancer patients: a risk particularly for carriers of the TGFB1 Pro25 variant.

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  • 1Department of Clinical Pharmacology, University Medical Center, Göttingen, Germany.

Abstract

PURPOSE:

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 AND MATERIALS:

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.

CONCLUSION:

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22000747
[PubMed - indexed for MEDLINE]
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