Health risks for ataxia-telangiectasia mutated heterozygotes: a systematic review, meta-analysis and evidence-based guideline.
Clin Genet
; 90(2): 105-17, 2016 Aug.
Article
em En
| MEDLINE
| ID: mdl-26662178
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Ataxia Telangiectasia
/
Isquemia Miocárdica
/
Proteínas Mutadas de Ataxia Telangiectasia
/
Neoplasias Gastrointestinais
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Guideline
/
Risk_factors_studies
/
Systematic_reviews
Limite:
Adult
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Clin Genet
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Holanda