Health risks for ataxia‐telangiectasia mutated heterozygotes: a systematic review, meta‐analysis and evidence‐based guideline
Health risks for ataxia‐telangiectasia mutated heterozygotes: a systematic review, meta‐analysis and evidence‐based guideline
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DOI：
10.1111/cge.12710
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发表时间：
2016-08
影响因子：
3.5
通讯作者：
Nielsen Os;N. Roeleveld;C. Weemaes;M. Jongmans;G. Janssens;A. Taylor;N. Hoogerbrugge;M. Willemsen
中科院分区：
文献类型：
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作者：
Nielsen Os;N. Roeleveld;C. Weemaes;M. Jongmans;G. Janssens;A. Taylor;N. Hoogerbrugge;M. Willemsen
共济失调-毛细血管扩张症（AT）是一种常染色体隐性遗传性神经退行性疾病，伴有免疫缺陷和癌症风险增加，由共济失调-毛细血管扩张症突变（ATM）基因突变引起。从逻辑上讲，血亲也可能携带致病性ATM突变。这种突变的女性携带者患乳腺癌的风险增加。对携带者的其他健康风险也有怀疑，但从未进行过系统的研究。因此，目前还没有针对携带者的循证指南。我们系统地分析了所有的文献，发现ATM突变携带者由于癌症和缺血性心脏病的死亡率而缩短了预期寿命（RR 1.7，95% CI 1.2 - 2.4）和癌症风险增加（RR 1.5，95%CI 0.9 - 2.4），特别是乳腺癌（RR女性3.0，95%CI 2.1 - 4.5）和消化道癌症。ATM杂合性和其他健康风险之间的关联已经提出，但缺乏明确的证据。基于这些结果，我们建议所有40 - 50岁的女性携带者和25岁以上的女性ATM c.7271T> G突变携带者都应接受乳腺癌的强化监测。此外，所有携带者都应了解导致心血管疾病和糖尿病发展的生活方式因素。
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.