Absence of mutations in the ATM gene in forty-seven cases of sporadic breast cancer

Abstract

Summary Epidemiological evidence points to an increased risk of breast cancer in ataxia telangiectasia (AT) heterozygote women. Previous attempts to screen early onset or familial breast cancer patients failed to confirm an association. The issue of AT and late onset sporadic breast cancer remained unresolved. We screened 47 women who developed later onset, sporadic breast cancer for ataxia telangiectasia mutated (ATM) mutations. No mutations were found.

The ATM gene is a target for epigenetic silencing in locally advanced breast cancer

“…As outlined in the seminal work of Swift et al (1987), and validated in subsequent studies (Easton, 1994;Athma et al, 1996), obligate ATM heterozygotes display an approximate fourfold elevated risk for developing breast cancer. Following the cloning of the ATM gene, several groups (FitzGerald et al, 1997;Bebb et al, 1999;Shafman et al, 2000) studied large cohorts of sporadic breast cancer patients and age-matched controls for nonsense or frame-shift mutations within the ATM gene. Neither group found evidence for a higher incidence of defective ATM alleles in the cancer patient cohort.…”

ATM variants 7271T>G and IVS10-6T>G among women with unilateral and bilateral breast cancer

“…These findings are consistent with two earlier studies: one study of the British families that first identified the 7271T4G mutation and reported a similarly large increased risk of breast cancer among three carriers of that mutation (RR ¼ 12.7, 95% CI 3.7 -45.8) (Stankovic et al, 1998); and a second study by Broeks (Broeks et al, 2000) of earlyonset female breast cancer, where three out of the seven ATM mutations found were IVS10-6T4G. While not all studies of ATM gene mutations demonstrate an excess risk of breast cancer (FitzGerald et al, 1997;Bebb et al, 1999;Shafman et al, 2000), studies that have screened for missense mutations (Athma et al, 1996;Teraoka et al, 2001) and those that have examined risk among family members of A-T patients (obligate heterozygotes) (Swift et al, 1987(Swift et al, , 1991Pippard et al, 1988;Borresen et al, 1990;Inskip et al, 1999;Olsen et al, 2001) have consistently found an elevated risk. Combined, these results provide evidence for an increased breast cancer risk associated with specific ATM gene mutations.…”

Immunoassay to Measure Ataxia-Telangiectasia Mutated Protein in Cellular Lysates

“…Furthermore, there is a fourfold increase in breast cancer for A-T carriers (heterozygotes) (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). This has led to the theory that many breast cancer patients in the general population are A-T carriers (22,23 ).…”