Our results indicate that the p.R215W mutation in the HCC1395 breast cancer cell line impairs NBN function, making this cell line a potentially useful cellular model for studying defective NBN protein within a mutant BRCA1 background.
The combined data are in line with an about 3-fold increase in breast cancer risk for female NBS heterozygotes (OR 3.1; 95%CI 1.4-6.6) and indicate that the 657del5 deletion and perhaps the R215W substitution contribute to inherited breast cancer susceptibility in Central and Eastern Europe.
Most of the 657del5 mutation carriers were found among patients with melanoma (4/105), non-Hodgkin lymphoma (2/42) and breast cancer (4/224) and of the 234 patients with colorectal carcinoma 3 carried the 657del5 mutation and 3 others the R215W molecular variant.