BESTIMMUNG DER GENETISCHEN EMPFINDLICHKEIT FUR DIE ENTWICKLUNG VON PLATTENEPITHELKARZINOMEN DES KOPF-HALS-BEREICHS MIT BLEOMYCIN-INDUZIERTER CHROMOSOMALER INSTABILITAT BESTIMMUNG DER GENETISCHEN EMPFINLICHKEIT FUR DIE ENTWICKLUNG VON PLATTENEPITHELKARZINOMEN DES KOPF-HALS-BEREICHS MIT BLEOMYCIN-INDUZIERTER CHROMOSOMALER INSTABILITAT

Background: Cigarette smoking is a well established risk factor for head and neck squamous cell carcinoma. However, data on smoking history are not sufficient to predict which patients are at high risk for the development of multiple primary tumors. It is hypothesized that both exposure to carcinogens and individual susceptibility determine cancer risk. The aim of this study was to investigate whether a possible individual susceptibility for head and neck squamous cell carcinoma was related to the outcome of the mutagen sensitivity assay, which was adopted from Hsu and colleagues. Methods: Cultured peripheral blood lymphocytes were treated for five hours with 30 mlU/ml of bleomycin, and sensitivity was estimated by the mean number of chromatid breaks per cell scored in 100 metaphases of duplicate cultures. Results: It was shown that using this standard mutagen sensitivity assay, a person's sensitivity can be reproducibly measured. Age had a significant but small contribution, whereas gender and tobacco and alcohol use had no influence on the outcome of the assay. Therefore, we consider this sensitivity for the DNA damaging effect of bleomycin constitutional. A retrospective study showed that the breaks per cell in head and neck squamous cell carcinoma patients (0.96 ± 0.31; n = 52) were significantly higher (p<0.001) than in control persons (0.77 ± 0.19 n = 50). In addition, head and neck cancer patients who had already developed multiple primary tumors had a break per cell level (1.20 ± 0.47; n=20) which was even significantly higher (p<0.025) than in patients with one primary tumor. Conclusion: We hypothesize that mutagen sensitivity reflects an individual's sensitivity vor DNA damaging agents. The extremely high sensitivity in patients with multiple primary tumors suggests that mutagen sensitivity is a phenotype reflecting a person's susceptibility to head and neck cancer. We postulate that mutagen sensitivity in combination with smoking history can be used to identify those patients at highest risk for the development of multiple primary tumors.