title: Health risks for ataxia-telangiectasia mutated heterozygotes: a systematic review, meta-analysis and evidence-based guideline.
abstract: Ataxia-telangiectasia (AT) is an autosomal recessive neurodegenerative disorder with immunodeficiency and an increased risk of developing cancer, caused by mutations in the ataxia-telangiectasia mutated (ATM) gene. Logically, blood relatives may also carry a pathogenic ATM mutation. Female carriers of such a mutation have an increased risk of breast cancer. Other health risks for carriers are suspected but have never been studied systematically. Consequently, evidence-based guidelines for carriers are not available yet. We systematically analyzed all literature and found that ATM mutation carriers have a reduced life expectancy because of mortality from cancer and ischemic heart diseases (RR 1.7, 95% CI 1.2-2.4) and an increased risk of developing cancer (RR 1.5, 95% CI 0.9-2.4), in particular breast cancer (RRwomen 3.0, 95% CI 2.1-4.5), and cancers of the digestive tract. Associations between ATM heterozygosity and other health risks have been suggested, but clear evidence is lacking. Based on these results, we propose that all female carriers of 40-50 years of age and female ATM c.7271T>G mutation carriers from 25 years of age onwards be offered intensified surveillance programs for breast cancer. Furthermore, all carriers should be made aware of lifestyle factors that contribute to the development of cardiovascular diseases and diabetes.
authors.affiliation: Department of Neurology - Pediatric Neurology, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: N J H
authors.initials: NJ
authors.lastname: van Os
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.|Department of Pediatrics, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Roeleveld
authors.affiliation: Department of Pediatrics, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands.
authors.forename: C M R
authors.initials: CM
authors.lastname: Weemaes
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: M C J
authors.initials: MC
authors.lastname: Jongmans
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht and Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: G O
authors.initials: GO
authors.lastname: Janssens
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: A M R
authors.initials: AM
authors.lastname: Taylor
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Hoogerbrugge
authors.affiliation: Department of Neurology - Pediatric Neurology, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: M A A P
authors.initials: MA
authors.lastname: Willemsen
mesh_terms: D000328:Adult; D001260:Ataxia Telangiectasia / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D019317:Evidence-Based Medicine; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008017:Life Expectancy; D008875:Middle Aged; D009154:Mutation; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D017410:Practice Guidelines as Topic; D012307:Risk Factors
chemical_list: C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM protein; ataxia-telangiectasia; heterozygote; risk factor