world cancer report - iarc

ATM AND BREAST CANCER
Whilst mutations in the BRCA1 and
BRCA2 genes contribute to familial breast
cancer risk, their contribution to sporadic
breast cancer is relatively minor. In the
latter disease category, genes frequently
altered in the general population, such as
the gene mutated in ataxia telangiectasia,
ATM, may be important risk factors.
Studies of ataxia telangiectasia families
initially revealed that ataxia telangiectasia
heterozygotic women hadan increased
risk of breast cancer. Taken together with
the estimation that 1% of the general population
are ATM heterozygotes, up to 8%
of breast cancer patients could thus be
ATM heterozygotes. One of the identifying
characteristics of ataxia telangiectasia
patients is that they are extremely sensitive
to ionizing radiation. Radiosensitivity,
seen as exaggerated acute or late tissue
reactions after radiotherapy, has been
reported in a significant proportion of
breast cancer patients. This suggests that
ataxia telangiectasia heterozygosity plays
a role in such radiosensitivity and in
breast cancer development. Loss of heterozygosity
in the region of the ATM gene
on chromosome 11 has been found in
about 40% of sporadic breast tumours.
Screening for ATM mutations in sporadic
breast cancer cases, regardless of
adverse response to radiotherapy, has not
achieve local disease control (surgery and
radiotherapy) and treat metastatic spread
(chemotherapy) [15]. Optimal surgery
may comprise a lumpectomy for a tumour
of