Oncogenotoxicology: A new approach to individual therapy and to the follow-up of patients

Abstract

21131 Background: The growing awareness of differences in inter-individual response to radiochemical exposure calls for a new approach in the therapy and follow-up of cancer patients. Results obtained by genotoxicological methods (Bonassi, 2006) showed that surrogate tissue could be used to predict cancer risk. Chromosome aberration (CA) and micronucleus (MN) assay enables:determination of radio- and chemosensitivity level in a patient, adjustment of therapy and detection of chromosomal rearrangements possibly related to the development of secondary cancer using fluorescent in situ hybridization (FISH) Methods: Ten women with breast cancer (BP) and 10 men with oropharinx cancer (OP) were analyzed before, during and after radiotherapy by CA and MN assay. Confounding parameters (age, diagnostics, smoking, drinking) were monitored and matched. Results were compared with 20 matched control subjects. The BP group received an irradiation dose of 60 Gy and the OP group of 62 Gy Results: Before therapy, the OP patients had a significantly higher MN frequency than BP and controls (23.2±4.9‰ versus 6.3±1.6 ‰ and 6.7±3.7‰). On measurements taken 6 and 12 months after the therapy, OP patients continued to have a significantly higher MN frequency than BP patients (60.2±11.4‰ vs. 8.4±2.4‰ and 30.7±4.7‰ vs.5.11±2.5‰, respectively). CA frequency was similar in both groups before therapy (2.5±1.1% in BC and 3.4±1.3% in OP; controls 1.2%). Twelve months after the therapy, the elimination of CA in OP patients was significantly slower than in BC patients (17.7±10.9% vs. 8±5.4%, respectively). As OP patients consumed more than 120 g/day of pure alcohol, it is possible that alcohol could have caused additional genome damage (Maffei, 2002). The highest inter-individual difference in genome damage was observed in BP patients Conclusions: The results show that the CA and MN assay are sensitive methods which can be used to introduce a new concept, oncogenotoxicology, whose goal is to improve the therapy results by evaluating inter-individual differences in response to radiochemical treatment and to improve the evaluation of risk of secondary cancer development. FISH in suspension (Wu, 2005) will allow automation of CA detection, and facilitate a more accurate prospective study of the same population. No significant financial relationships to disclose.