Increased risk of breast cancer following irradiation for Hodgkin's disease is not a result of ATM germline mutations.
OBJECTIVE
Long-term survivors of Hodgkin's disease who received mantle-field irradiation at a young age have a strongly increased risk of developing breast cancer. The purpose of this study was to investigate whether this increased risk was substantially greater among women heterozygous for a germline mutation in the ataxia-telangiectasia gene (ATM).


METHODS
Thirty-two patients were selected who had developed breast cancer at least 10 years following irradiation for Hodgkin's disease before the age of 45 years. In these patients, the complete open reading frame of the ATM gene was analysed for the presence of germline mutations using the protein truncation test and two mutation-specific tests, followed by genomic sequencing.


RESULTS
No A-T disease causing germline mutations were found in these selected Hodgkin patients. However, several alternative splicing events were detected which might influence protein expression levels.


CONCLUSIONS
The data suggest that truncating mutations in the ATM gene are not a major component underlying the increased risk of breast cancer following Hodgkin's disease.
Broeks
A
A
Department of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam.
Russell
N S
NS
Floore
A N
AN
Urbanus
J H
JH
Dahler
E C
EC
van T Veer
M B
MB
Hagenbeek
A
A
Noordijk
E M
EM
Crommelin
M A
MA
van Leeuwen
F E
FE
van T Veer
L J
LJ
D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics*; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D004262:DNA Restriction Enzymes / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D017353:Gene Deletion; D018095:Germ-Line Mutation; D006689:Hodgkin Disease / Q000532:radiotherapy*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D016366:Open Reading Frames; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D012306:Risk; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D004262:DNA Restriction Enzymes