BACKGROUND: Mutations 657del5 and R215W in exon 6 of tumor suppressor gene NBS I are found in 1% Slavic populations. Increased occurrence of cancer was repeatedly reported in adult relatives of patients with Nijmegen breakage syndrome. Among children with oncological problematic, nonsignificantly increased frequency of NBS1 heterozygotes was found, which seems not to play any important role in cancerogenesis in childhood. However, the proportion of NBS heterozygotes among adult patients with malignancies could be significant and their therapy and follow up should respect their hyperradiosensitivity. METHODS AND RESULTS: Mutations in exon were studied in 706 adult patients with malignancies. We found 5 NBS heterozygotes, which not more than the population prevalence (1:129-165). Increased frequency of NBS heterozygotes was found among patients with colon and rectal cancer (2/101), breast cancer (1/60), skin malignancies (1/98). CONCLUSIONS: Surprisingly only one NBS heterozygote was found among 228 patients with nonHodgkin lymphoma, the malignancy which is a common complication in NBS homozygotes. Other types of malignancies were uncommon and only one R215W heterozygote was found. Comparison frequency of NBS heterozygotes with incidence NBS among person older than 70 years shows significant difference. Prevention of malignancies by avoidance from ionisation could be realized also in relatives of patients after identification of their genotype.

Oddelení klinické genetiky Ustavu biologie a lékarské genetiky 2 LF UK Praha

The NBN founder mutation-Evidence for a country specific difference in age at cancer manifestation