Integrated DNA Repair Capacity and NER Gene Expression for Improving Risk Prediction in Head and Neck Squamous Cell Carcinoma

Abstract

Objective

DNA repair plays a critical role in the development of smoking-related cancers. We hypothesized that DNA repair capacity (DRC) and nucleotide excision repair (NER) mRNA expression are associated with increased head and neck squamous cell carcinoma (HNSCC) risk in the Chinese population.

Methods

We conducted a case-control study including 349 patients with HNSCC and 316 cancer-free controls. DRC and NER mRNA expression levels were measured in lymphoblastoid cells exposed to benzo[a]pyrene diol epoxide (BPDE). Correlations between DRC and NER mRNA expression were analyzed, and their associations with HNSCC risk were evaluated.

Results

The mean DRC was significantly lower in patients with HNSCC (9.72% ± 2.25%) than in healthy controls (10.81% ± 2.63%, P < 0.001). Compared with individuals with higher DRCs, those with lower DRCs had a significantly greater risk of HNSCC (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 1.60–3.10, P < 0.001; P_trend < 0.001). Correlation analyses demonstrated significant associations between DRC and the expression of XPA and XPB. Moreover, predictive models combining DRC with XPA and/or XPB mRNA expression significantly improved risk prediction, as evidenced by increased area under the curve (AUC) values (P < 0.05).

Conclusions

Suboptimal DRC and reduced expression of key NER genes, particularly XPA and XPB, are associated with increased HNSCC risk. Integrating these two NER biomarkers may provide a novel and improved model for HNSCC risk assessment.

Keywords

Head and neck neoplasms / DNA repair / Nucleotide excision repair / Cancer susceptibility / Risk assessment / Biomarkers / Case-control studies

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Funding

Natural Science Foundation of China(82571316)

Natural Science Basic Research Program of Shaanxi Province(2023-JC-YB-791)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to the Huazhong University of Science and Technology