Can gene therapy be used to prevent cancer? Gene therapy for aldehyde dehydrogenase 2 deficiency.
Can gene therapy be used to prevent cancer? Gene therapy for aldehyde dehydrogenase 2 deficiency.
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基因治疗可以用来预防癌症吗？乙醛脱氢酶2缺乏症的基因治疗。
DOI：
10.1038/s41417-021-00399-1
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发表时间：
2022-07
影响因子：
6.4
通讯作者：
Crystal, Ronald G.
中科院分区：
文献类型：
--
作者：
Montel, Rachel A.;Munoz-Zuluaga, Carlos;Stiles, Katie M.;Crystal, Ronald G.
大约 8% 的世界人口和 35% 至 45% 的东亚人是遗传性疾病乙醛脱氢酶 2 (ALDH2) 缺乏症的携带者。 ALDH2 在肝脏代谢乙醇中发挥核心作用。常见的E487K变体缺乏ALDH2功能；当消耗乙醇时，乙醛（乙醇代谢的中间产物）会在全身积累。在缺乏 ALDH2 的个体中，摄入乙醇会严重导致“酒精潮红综合症”，伴有面部潮红、心动过速、恶心和头痛。长期饮酒后，ALDH2 缺乏与多种疾病相关，包括罹患呼吸消化道癌症的极高风险。乙醛是一种已知的致癌物质。与 ALDH2 缺乏和癌症风险相关的流行病学数据令人震惊：中度至大量乙醇消耗的 ALDH2 纯合子患食道癌的风险增加 7 至 12 倍，这使得 ALDH2 缺乏成为与癌症风险增加相关的最常见遗传性疾病。在这篇综述中，我们总结了 ALDH2 的遗传学和生物化学、与 ALDH2 缺乏相关的癌症风险的流行病学、与 ALDH2 缺乏相关的乙醇消耗的代谢后果以及纠正 ALDH2 缺乏及其相关癌症风险的基因治疗策略。为了降低呼吸消化道癌症的风险，在 ALDH2 是一种遗传性疾病且 ALDH2 主要在肝脏中发挥作用的背景下，ALDH2 缺乏是应用腺相关病毒介导的肝脏定向基因治疗预防癌症的理想靶点。
Approximately 8% of the world population and 35 to 45% of East Asians are carriers of the hereditary disorder, aldehyde dehydrogenase 2 (ALDH2) deficiency. ALDH2 plays a central role in the liver to metabolize ethanol. With the common E487K variant, there is a deficiency of ALDH2 function; when ethanol is consumed, there is a systemic accumulation of acetaldehyde, an intermediate product in ethanol metabolism. In ALDH2 deficient individuals, ethanol consumption acutely causes the “Alcohol Flushing Syndrome” with facial flushing, tachycardia, nausea and headaches. With chronic alcohol consumption, ALDH2 deficiency is associated with a variety of disorders, including a remarkably high risk for aerodigestive tract cancers. Acetaldehyde is a known carcinogen. The epidemiologic data relating to the association of ALDH2 deficiency and cancer risk are striking: ALDH2 homozygotes that are moderate to heavy consumers of ethanol have a 7- to 12-fold increased risk for esophageal cancer, making ALDH2 deficiency the most common hereditary disorder associated with an increased cancer risk. In this review, we summarize the genetics and biochemistry of ALDH2, the epidemiology of cancer risk associated with ALDH2 deficiency, the metabolic consequences of ethanol consumption associated with ALDH2 deficiency and gene therapy strategies to correct ALDH2 deficiency and its associated cancer risk. With the goal of reducing the risk of aerodigestive tract cancers, in the context that ALDH2 is a hereditary disorder and ALDH2 functions primarily in the liver, ALDH2 deficiency is an ideal target for the application of adeno-associated virus-mediated liver directed gene therapy to prevent cancer.
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影响因子：
11
作者：
Chang JS;Hsiao JR;Chen CH
通讯作者：
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影响因子：
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作者：
Gao YH;Wu ZX;Xie LQ;Li CX;Mao YQ;Duan YT;Han B;Han SF;Yu Y;Lu HJ;Yang PY;Xu TR;Xia JL;Chen GQ;Wang LS
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2.3
作者：
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通讯作者：
Theruvathu, JA
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影响因子：
5.3
作者：
Gao, Yong;He, Yisha;Shen, Hongbing
通讯作者：
Shen, Hongbing
影响因子：
5.8
作者：
ERIKSSON, CJP;SIPPEL, HW
通讯作者：
SIPPEL, HW