Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition

“…are essentially the result of misrepaired dsb (Wu et al, 1996; Boei et al, 2000; Fomina et al, 2000) by the NHEJ repair system (Jeggo, 1998; Takata et al, 1998; Rothkamm et al, 2001), the mechanisms involved in the formation of G2 chromatid breaks are not fully understood yet and different…”

“Breast cancer is the most common type of cancer in females, accounting for approximately 18% of all cancer cases in women worldwide (Parkin et al, 1988).”

“Per slide 500 binucleate cells (BN) were scored (light microscopy, 4006) according to the criteria of Fenech (1993).”

“For further analysis we considered three subgroups in our total group of breast cancer patients: (1) a subgroup of patients that met criteria 1 and 2 (see Materials and Methods) and in which a mutation in BRCA1/2 was detected (BRCA1, n=4; BRCA2, n=7); (2) a subgroup of patients that met criteria 1 and 2 but without a…”

“Although recent studies have shown that G0/G1 chromosomal aberrations are essentially the result of misrepaired dsb (Wu et al, 1996; Boei et al, 2000; Fomina et al, 2000) by the NHEJ repair system (Jeggo, 1998; Takata et al, 1998; Rothkamm et al, 2001), the mechanisms involved in the formation of G2 chromatid breaks a…”

“…aberrations are essentially the result of misrepaired dsb (Wu et al, 1996; Boei et al, 2000; Fomina et al, 2000) by the NHEJ repair system (Jeggo, 1998; Takata et al, 1998; Rothkamm et al, 2001), the mechanisms involved in the formation of G2 chromatid breaks are not fully understood yet…”

“Apart from the population characteristics, differences in the MN assay protocols may also be responsible for the differences between the results of Scott et al (1998, 1999) and present work.”

“The exact role of BRCA1 and BRCA2 in repair of DNA damage by ionising radiation is not yet fully understood (Abbott et al, 1998; Wang et al, 2001).”

“…2000) by the NHEJ repair system (Jeggo, 1998; Takata et al, 1998; Rothkamm et al, 2001), the mechanisms involved in the formation of G2 chromatid breaks are not fully understood yet and different hypotheses have been proposed in literature (Parshad et al, 1996; Bryant 1998; Terzoudi et al, 2000).”

“These findings are in agreement with the data of Roberts et al (1999), who also found no significant differences between pre- and post-therapy G2 values in breast cancer patients.”

“Apart from the population characteristics, differences in the MN assay protocols may also be responsible for the differences between the results of Scott et al (1998, 1999) and present work.”

“…a substantial proportion of breast cancer patients may be predisposed to breast cancer through mutations in low penetrance genes, which may be genes involved in the processing of DNA damage (Teare et al, 1994; Roberts et al, 1999; Scott et al, 1999; Burrill et al, 2000; Peto and Houlston, 2001).”

“The results demonstrated that the group of breast cancer patients with a known or putative genetic predisposition was on the average more radiosensitive than a population of healthy women, and this with the G2 as well as with the high dose rate and low dose rate micronucleus assay.”

“Taking into account an age dependent increase of 0.58 MN/year for a female population (Thierens et al, 2000), the observed increase in the mean spontaneous MN yield in the patient group cannot be attributed to the age effect alone, but may be partly due to the radio- or/and chemotherapy that some…”

“These results are in agreement with the enhanced chromosomal radiosensitivity observed in sporadic breast cancer patients (Scott et al, 1994, 1999; Terzoudi et al, 2000; Riches et al, 2001).”

“In breast cancer patients the elevated chromosomal radiosensitivity is confirmed in several independent studies (Scott et al, 1994, 1998; Parshad et al, 1996; Patel et al, 1997; Terzoudi et al, 2000; Baria et al, 2001a; Riches et al, 2001).”

“LDR was applied to allow repair and by this to discriminate in a better way between sensitive and non-sensitive individuals (Jones et al, 1995; Scott et al, 1998).”

“These results are in agreement with the enhanced chromosomal radiosensitivity observed in sporadic breast cancer patients (Scott et al, 1994, 1999; Terzoudi et al, 2000; Riches et al, 2001).”

“…recent studies have shown that G0/G1 chromosomal aberrations are essentially the result of misrepaired dsb (Wu et al, 1996; Boei et al, 2000; Fomina et al, 2000) by the NHEJ repair system (Jeggo, 1998; Takata et al, 1998; Rothkamm et al, 2001), the mechanisms involved in the formation of G2…”

“Although recent studies have shown that G0/G1 chromosomal aberrations are essentially the result of misrepaired dsb (Wu et al, 1996; Boei et al, 2000; Fomina et al, 2000) by the NHEJ repair system (Jeggo, 1998; Takata et al, 1998; Rothkamm et al, 2001), the mechanisms involved in the formation of G2 chromatid breaks a…”

“Although recent studies have shown that G0/G1 chromosomal aberrations are essentially the result of misrepaired dsb (Wu et al, 1996; Boei et al, 2000; Fomina et al, 2000) by the NHEJ repair system (Jeggo, 1998; Takata et al, 1998; Rothkamm et al, 2001), the mechanisms involved in the formation of…”

“For the micronucleus assay lymphocytes were exposed in vitro to 3.5 Gy 60Co g-rays at a high dose rate or low dose rate.”

“After 70 – 72 h incubation in a CO2 incubator at 378C the cultures were irradiated with a dose of 0.4 Gy Co-60 g rays at 378C (Vral et al, 2002).”

“The cells were stored overnight in the refrigerator (48C) and fixed for another three times with methanol : acetic acid (10 : 1) (Vral et al, 1994).”

“…a substantial proportion of breast cancer patients may be predisposed to breast cancer through mutations in low penetrance genes, which may be genes involved in the processing of DNA damage (Teare et al, 1994; Roberts et al, 1999; Scott et al, 1999; Burrill et al, 2000; Peto and Houlston, 2001).”

“Women fulfilling one of the following selection criteria were analysed for presence of a mutation in BRCA1 and BRCA2 as described (Claes et al, 1999a,b).”

“Gentile et al (1999) suggest that these patients have unidentified genes involved in initiation and/or progression of breast cancer, situated on chromosome 11.”

“Although recent studies have shown that G0/G1 chromosomal aberrations are essentially the result of misrepaired dsb (Wu et al, 1996; Boei et al, 2000; Fomina et al, 2000) by the NHEJ repair system (Jeggo, 1998; Takata et al, 1998; Rothkamm et al, 2001), the mechanisms involved in the formation of…”

“It was shown that tumours in BRCA1/BRCA2 carriers are more sensitive to ionising radiation [48,49].”