Identification of common genetic variants in KCNQ family genes associated with gastric cancer survival in a Chinese population.

Abstract

The KCNQ family of genes ( KCNQ1- KCNQ5), encoding voltage-gated K ⁺ (Kv) channels, have been demonstrated to play potential pathophysiological roles in cancers. However, the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear. In this study, a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival (OS). Based on the survival evaluation of all five KCNQ family genes, KCNQ1 was selected for subsequent genetic analysis. In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants, we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients (adjusted hazards ratio [HR] = 0.84, 95% confidence interval [CI]: 0.72-0.98, P = 0.023). Subsequently, a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants. The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure. Furthermore, we observed that gastric cancer patients with downregulated KCNQ1 expression had a poorer survival across multiple public datasets. The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer, providing novel insights into the progression and survival of the disease.