Observational studyBMC cancer2021
ALDH2 polymorphism rs671 is a predictor of PD-1/PD-L1 inhibitor efficacy against thoracic malignancies.
Observational study in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 14 citations in OpenAlex.
- A Bayesian phase I/II design to determine subgroup-specific optimal dose for immunotherapy sequentially combined with radiotherapy.Pharmaceutical statistics · 2023Trial
- Regulatory polymorphisms ofJournal for immunotherapy of cancer · 2025Article
- [Research progress of aldehyde dehydrogenase type 2 in head and neck malignant tumors].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- Expression pattern and prognostic significance of aldehyde dehydrogenase 2 in lung adenocarcinoma as a potential predictor of immunotherapy efficacy.Cancer innovation · 2025Article
- Article
- Asian flush gene variant increases mild cognitive impairment risk: a cross-sectional study of the Yoshinogari Brain MRI Checkup Cohort.Environmental health and preventive medicine · 2024Article
- ALDH2 polymorphism rs671 and alcohol consumption: possible explanatory factors for race/ethnic differences in bone density.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Article
- ALDH2 rs671 variant allele is associated with higher energy intake in middle-aged and elderly Japanese who routinely consume alcohol.Environmental health and preventive medicine · 2023Article
- Variant Allele ofVaccines · 2022Article
- Challenges of the Immunotherapy: Perspectives and Limitations of the Immune Checkpoint Inhibitor Treatment.International journal of molecular sciences · 2022Review
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Authors and funding
5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundAldehyde dehydrogenase 2 (ALDH2) plays an important role in the endogenous aldehyde detoxification of various types of cells. ALDH2*2, a variant allele of the ALDH2 polymorphism rs671, leads to decreased enzymatic activity. ALDH2*2 may enhance tumor antigen presentation due to aldehyde-induced DNA damage while suppressing peripheral blood T cell counts and T cell activation.
methodsOn the basis of our hypothesis that rs671 affects the sensitivity of immune checkpoint inhibitors (ICIs), we evaluated the effects of rs671 on patients with thoracic malignancies who started ICI therapy in 2016-2019. The cohort consisted of 105 cases, including 64 cases with adenocarcinoma and 30 cases with squamous cell carcinoma, 49 of whom were ALDH2*2 carriers. The first ICI was PD-1/PD-L1 inhibitor (Nivolumab, Pembrolizumab, or Atezolizumab) in all cases.
resultsThe best response to anti-PD-1/PD-L1 therapy (partial response/stable disease/progressive disease) was 36%/50%/14% in the rs671(-) cases; however, the response was relatively poor in the rs671(+) cases (27%/29%/45%, respectively) (p = 0.002). The hazard ratio (95% confidence interval) of disease progression within the observation period of 6 months for the rs671(+) cases was estimated to be 5.0 (2.5-10) after the adjustment for covariates, including sex, Brinkman index, treatment line, tumor tissue programmed death-ligand 1 positivity rate, tumor tissue EGFR mutation. This association was also maintained in a stratified analysis, suggesting that ALDH2*2 is an independent negative predictive factor for the short-term prognosis of anti-PD-1/PD-L1 therapy. Thus, the progression-free survival (PFS) ratio of the rs671(+) cases decreased rapidly after ICI initiation but was eventually higher than that of the rs671(-) cases (restricted mean survival time in 12 months from 2 to 3 years afterward was 1.3 times that of the rs671(-) cases). Moreover, the highest PFS ratio after 2 years among sub-groups was found in the first-line treatment sub-group of rs671(+) group (40%).
conclusionsOur study suggests that rs671 may be an accurate and cost-effective predictor of PD-1/PD-L1 inhibitor treatment, in which optimal case selection is an important issue.
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