BLMH1 single nucleotide polymorphism correlation with bleomycin chemotherapy in patients with testicular germ cell tumors.

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e15100 Background: Bleomycin, the main component of chemotherapy protocol for metastatic testicular germ-cell tumor (TGCT), may be inactivated by bleomycin hydrolase, encoded by BLMH1 gene. SNP A1450G is thought to be involved in controling enzymatic activity and thus the level of bleomycin-induced DNA damage. We suggested hypotesis that this SNP A1450G might influence toxicity in TGCT patients. Methods: Fiftynine patients with metastatic TGCT (6 seminomas, 14 nonseminomas and 39 with mixed germ cell tumors) were treated with three (10 patients) or four cycles (47 patients) of BEP chemotherapy (bleomycin/etoposide/cisplatin), except for 2 patients with bleomycin toxicity who were treated with 1 and 2 cycles of BEP. Blood samples of 59 patients were analysed using the real-time PCR method performed by ABI PRISM 7000 Sequence Detection System (Applied Biosystems) and pre-developed TaqMan SNP genotyping assay (rs1050565) according to the manufactures' instructions Results: We observed a wide range of adverse events casued by toxicity of bleomycin: cough, dyspnea, pneumonitis, pulmonary fibrosis, nail changes, hyperpigmentation, hypersensitivity, pruritus, leukocytopenia, vomiting, nausea and the fever. Two patients revealed severe adverse events (who were treated with 1 and 2 cycles of BEP), one a pulmonary fibrosis (x-ray verified) and the second as a significant dyspnea.The most common adverse effects were dermatological (hyperpigmentation, pruritus, hypersensitivity and nail changes) as well as fever. Patients with AG or GG genotypes developed more adverse events (25) than patients with AA (16) although results didn't reach statistical significance. Conclusions: Our results suggests that application of SNPs in future as a routine method will enable individual approach and recognition of patients who are genetically predisposed for higher toxicological effects of bleomycin. It can be expected that as number of subjects in this cohort will increase statistical significance will be reached. No significant financial relationships to disclose.