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

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.

Keywords: CRCI; breast cancer survivors; chemotherapy; cognitive impairment.

FIGURE 1

Technical process of this study

FIGURE 2

Comparison of cognitive abilities of patients before and after chemotherapy. (A) Score of MMSE of those with ALDH2_rs671_GG. (B) Score of DST of those with ALDH2_rs671_GG. (C) Score of VFT of those with ALDH2_rs671_GG. (D) Score of MMSE of those with ALDH2_rs886205_GG. (E) Score of DST of those with ALDH2_rs886205_GG. (F) Score of VFT of those with ALDH2_rs886205_GG. BC means before chemotherapy, AC means after chemotherapy, *p < 0.05, **p < 0.01, ****p < 0.0001, and p < 0.05 were considered significant

FIGURE 3

Comparison of cognitive abilities of patients before and after chemotherapy. (A) Score of MMSE of those with ALDH2_rs4648328_CC. (B) Score of DST of those with ALDH2_rs4648328_CC. (C) Score of VFT of those with ALDH2_rs4648328_CC. (D) Score of MMSE of those with ALDH2_rs4767944_TT. (E) Score of DST of those with ALDH2_rs4767944_TT. (F) Score of VFT of those with ALDH2_rs4767944_TT. BC means before chemotherapy, AC means after chemotherapy, *p < 0.05, **p < 0.01, ****p < 0.0001, and p < 0.05 were considered significant.

FIGURE 4

Correlation analysis of cognitive outcomes in patients with single‐nucleotide polymorphisms characteristic of cognitive decline after chemotherapy. (A) Correlation between MMSE and VFT in ALDH2_rs671_GG patients after chemotherapy. (B) Correlation between MMSE and DST in ALDH2_rs886205_GG patients after chemotherapy. (C) Correlation between DST and VFT in ALDH2_rs4648328_CC patients after chemotherapy. (D) Correlation between DST and VFT in ALDH2_rs4767944_TT patients after chemotherapy

FIGURE 5

Expression of ALDH2 in the brain. (A) Expression of ALDH2 in different parts of the brain. (B) Expression of ALDH2 in different parts of the hippocampal formation. (C) Expression of ALDH2 in different parts of the amygdala

FIGURE 6

Scientific value of this research