Analýza mutace [657DEL(5)] v exonu 6 genu NBS-1 u 472 pacientek se sporadickým karcinomem prsu v České Republice

Background: Nijmegen breakage syndrome (NBS) caused by mutation [657del(5)] in exon 6 of NBS-1 is an autosomal recessive disorder with microcephaly, immunodeficiency, radiosensitivity, and predisposition to lymphoid malignancies. Recently, high frequency of this NBS-1 mutation was found in some Slavic populations. Because NBS-1 heterozygotes may have high incidence of neoplastic changes, there is an urgent need to clarify the role of NBS-1 mutation in breast cancer carcinogenesis. Methods: We analyzed the NBS-1 mutation [657del(5)] in exon 6 in 472 sporadic breast cancer patients treated in the Department of Oncology, Charles University Prague. DNA was extracted from peripheral blood monocytes. Subsequently two PCRs for each sample were carried out. Reaction was visualized using electrophoresis on agarose gel. Agarose gel wells with both the NBS-1 gene-specific band and internal control band were interpreted as positive. Wells with internal control only were interpreted as negative. PCR from samples giving neither an internal control band nor specific band were repeated. DNA samples obtained from a previously typed NBS family were used as a positive control. Results: Based on previously published data we expect to find at least 5 mutation carriers. Surprisingly, in our population of 472 subjects there was no mutation identified. Conclusion: Based on results of this study there is no relationship between NBS-1 mutation and breast cancer incidence.