The 5382insC mutation was found in 20 of 7920 (0.25%) population DNA samples and in 14 of 570 (2.46%) breast cancer samples; the T300G mutation was detected in 4 population samples (0.05%) and in 2 breast cancer samples (0.35%); the 185delAG or 4153delA mutations were not identified in any of the 7920 samples and were detected in 1 (0.18%) breast cancer case each.
Comparing these data with the population frequency, we calculated the relative risk of breast cancer for 5382insC mutation at OR = 17 and for 300T >G mutation at OR = 26.
Screening for three mutations (5382insC, 4154delA and 300T>G) was carried out in 55 breast cancer and 66 ovarian cancer patients, and for two mutations, 5382insC and 4154delA, in 376 unselected patients with any cancer (including 51 breast cancer and 29 ovarian cancers) and 215 women with any gynaecological tumour.
We found that an exogenous BRCA1 gene strongly inhibited telomerase enzymatic activity in human prostate and breast cancer cell lines and caused telomere shortening in cell lines expressing wild-type BRCA1 (wtBRCA1) but not a tumor-associated mutant BRCA1 (T300G). wtBRCA1 inhibited the expression of the catalytic subunit (telomerase reverse transcriptase [TERT]) but had no effect on the expression of a subset of other components of the telomerase holoenzyme or on the expression of c-Myc, a transcriptional activator of TERT.