When less is more: The association between the expression of polymorphic CYPs and AFB1-induced HCC

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL European Journal of Clinical Investigation Pub Date : 2024-08-05 DOI:10.1111/eci.14297

Asmaa Ashraf Mohamed, Monica Armanious, Rana W. Bedair, Nada Sherif Amin, Hend M. El Tayebi

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Abstract

Background

An individual’s genetic fingerprint is emerging as a pivotal predictor of numerous disease- and treatment-related factors. Single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes play key roles in an individual’s exposure to a malignancy-associated risk, such as Aflatoxin B1 (AFB1)-induced hepatocellular carcinoma (HCC).

Aim

This study aimed at reviewing literature on the polymorphisms that exist in CYP enzymes and their possible link with susceptibility to AFB1-induced HCC.

Materials & Methods

A set of keywords associated with the study subject of interest was used to search the Google Scholar and the PubMed database. The last ten years’ worth of research projects were included in the results filter. The research involved HCC patients and any connection between polymorphic forms of CYP enzymes and their susceptibility to AFB1-induced HCC, including older but significant data.

Results

Variations in CYP1A2 and CYP3A4 were reported to impact the rate and magnitude of AFB1 bio-activation, thus influencing an individual’s vulnerability to develop HCC. In HCC patients, the activity of CYP isoforms varies, where increased activity has been reported with CYP2C9, CYP2D6, and CYP2E1, while CYP1A2, CYP2C8, and CYP2C19 exhibit decreased activity. CYP2D6*10 frequency has been discovered to differ considerably in HCC patients. Rs2740574 (an upstream polymorphism in CYP3A4 as detected in CYP3A4*1B) and rs776746 (which affects CYP3A5 RNA splicing), both of which influence CYP3A expression, thus impacting the variability of AFB1-epoxide adducts in HCC patients.

Discussion

CYP1A2 is the primary enzyme accountable for the formation of harmful AFBO globally. CYP3A4, CYP3A5, CYP3A7, CYP2B7, and CYP3A3 are also implicated in the bio-activation of AFB1 to mutagenic metabolites. It is thought that CYP3A4 is the protein that interacts with AFB1 metabolism the most.

Conclusion

Polymorphic variants of CYP enzymes have a functional impact on the susceptibility to AFB1-induced HCC. Outlining such variation and their implications may provide deeper insights into approaching HCC in a more personalized manner for guiding future risk-assessment, diagnosis, and treatment.

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少即是多多态 CYPs 的表达与 AFB1 诱导的 HCC 之间的关联。

背景：个人的遗传指纹正在成为众多疾病和治疗相关因素的关键预测因子。药物代谢酶中的单核苷酸多态性（SNPs）在个体暴露于恶性肿瘤相关风险（如黄曲霉毒素 B1（AFB1）诱导的肝细胞癌（HCC））中发挥着关键作用：使用一组与研究主题相关的关键词在谷歌学术和 PubMed 数据库中进行搜索。结果筛选包括过去十年的研究项目。研究涉及 HCC 患者及其 CYP 酶多态形式与 AFB1 诱导的 HCC 易感性之间的任何联系，包括较早但重要的数据：结果：据报道，CYP1A2 和 CYP3A4 的变异会影响 AFB1 生物活化的速度和程度，从而影响个人患 HCC 的易感性。在 HCC 患者中，CYP 同工酶的活性各不相同，有报告称 CYP2C9、CYP2D6 和 CYP2E1 的活性增加，而 CYP1A2、CYP2C8 和 CYP2C19 的活性降低。已发现 CYP2D6*10 频率在 HCC 患者中差异很大。Rs2740574（CYP3A4*1B中检测到的CYP3A4上游多态性）和rs776746（影响CYP3A5 RNA剪接）都会影响CYP3A的表达，从而影响HCC患者中AFB1-环氧化物加合物的变化：讨论：CYP1A2 是在全球范围内形成有害 AFBO 的主要酶。CYP3A4、CYP3A5、CYP3A7、CYP2B7 和 CYP3A3 也参与了 AFB1 转化为诱变代谢物的生物活化过程。据认为，CYP3A4 是与 AFB1 代谢相互作用最大的蛋白质：结论：CYP 酶的多态变异对 AFB1 诱导的 HCC 易感性具有功能性影响。概述这种变异及其影响可为以更个性化的方式处理 HCC 提供更深入的见解，从而指导未来的风险评估、诊断和治疗。

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来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.