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乙醛脱氢酶 2 多态性与接受化疗的乳腺癌患者化疗相关认知功能障碍相关。

Aldehyde dehydrogenase 2 polymorphism is associated with chemotherapy-related cognitive impairment in patients with breast cancer who receive chemotherapy.

机构信息

Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China.

Cancer and Cognition Laboratory, Anhui Medical University, Hefei, Anhui, China.

出版信息

Cancer Med. 2023 Mar;12(5):5209-5221. doi: 10.1002/cam4.5319. Epub 2022 Oct 6.

Abstract

BACKGROUND

Chemotherapy-related cognitive impairment (CRCI) is a common but easily overlooked condition that markedly affects the quality of life (QOL) of patients with breast cancer. The rs671 is a common gene polymorphism of aldehyde dehydrogenase 2 (ALDH2) in Asia that is involved in aldehyde metabolism and may be closely related to CRCI. However, no study has yet summarised the association between ALDH2 and CRCI.

METHODS

This study enrolled one hundred and twenty-four patients diagnosed with breast cancer according to the pathology results, genotyped for ALDH2 single-nucleotide polymorphisms (SNP) to explore these. The mini-mental state exam (MMSE), verbal fluency test (VFT), and digit span test (DST) results were compared in these patients before and after chemotherapy (CT).

RESULTS

We found that patients with ALDH2 gene genotypes of rs671_GG, rs886205_GG, rs4648328_CC, and rs4767944_TT polymorphisms were more likely to suffer from cognitive impairment during chemotherapy. A trend toward statistical significance was observed for rs671_GG of DST (z = 2.769, p = 0.006), VFT (t = 4.624, P<0.001); rs886205_GG of DST (z = 3.663, P<0.001); rs4648328_CC of DST (z = 2.850, p = 0.004), VFT (t = 3.477, p = 0.001); and rs4767944_TT of DST (z = 2.967, p = 0.003), VFT (t = 2.776, p = 0.008). The cognitive indicators of these patients significantly decreased after chemotherapy (p < 0.05). The difference in ALDH2 rs671 was most obvious.

CONCLUSION

Our results showed what kinds of ALDH2 genotyped patients that are more likely to develop CRCI. In the future, it may be possible to infer the risk of CRCI by detecting the single-nucleotide locus of ALDH2 that is conducive to strengthening clinical interventions for these patients and improving their QOL. More importantly, this study has important implications for Asian women with breast cancer as ALDH2 rs671 is a common polymorphism in Asians.

摘要

背景

化疗相关性认知障碍(CRCI)是一种常见但易被忽视的病症,显著影响乳腺癌患者的生活质量(QOL)。rs671 是亚洲人乙醛脱氢酶 2(ALDH2)的常见基因多态性,参与醛类代谢,可能与 CRCI 密切相关。然而,目前尚无研究总结 ALDH2 与 CRCI 之间的关系。

方法

本研究纳入了 124 例根据病理结果诊断为乳腺癌的患者,对 ALDH2 单核苷酸多态性(SNP)进行基因分型,以探讨这些患者的情况。在化疗(CT)前后,比较这些患者的简易精神状态检查(MMSE)、词语流畅性测试(VFT)和数字跨度测试(DST)结果。

结果

我们发现,ALDH2 基因 rs671_GG、rs886205_GG、rs4648328_CC 和 rs4767944_TT 基因型的患者在化疗期间更易发生认知障碍。DST 的 rs671_GG(z=2.769,p=0.006)、VFT(t=4.624,P<0.001);rs886205_GG 的 DST(z=3.663,P<0.001);rs4648328_CC 的 DST(z=2.850,p=0.004)、VFT(t=3.477,p=0.001);rs4767944_TT 的 DST(z=2.967,p=0.003)、VFT(t=2.776,p=0.008)显示出统计学趋势。这些患者的认知指标在化疗后明显下降(p<0.05)。ALDH2 rs671 的差异最为明显。

结论

我们的研究结果表明,哪些类型的 ALDH2 基因型患者更容易发生 CRCI。未来,通过检测 ALDH2 的单核苷酸位点,可能可以推断出 CRCI 的风险,有利于加强对这些患者的临床干预,提高他们的生活质量。更重要的是,这项研究对亚洲乳腺癌女性具有重要意义,因为 ALDH2 rs671 是亚洲人的常见多态性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82e5/10028021/5b54984dbd3f/CAM4-12-5209-g001.jpg

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