Jing Xin, Yun Yuhui, Ji Xiang, Yang Ende, Li Pei
Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710038, People's Republic of China.
Pharmgenomics Pers Med. 2023 Aug 25;16:795-804. doi: 10.2147/PGPM.S424326. eCollection 2023.
Cancer development and tumor immune microenvironment remodeling are closely linked to pyroptosis and inflammasome activation. However, little information is available in single nucleotide polymorphisms (SNPs) in pyroptosis and inflammasome-related genes in patients with lung cancer. This study aims to evaluate the associations between pyroptosis-related gene ( and ) polymorphisms and the risk of lung cancer.
The MassARRAY platform was used to genotype six SNPs of the and genes in 660 lung cancer cases and 660 controls.
Individuals with rs35829419-A, rs385076-C, and rs775882-T alleles exhibited a higher risk of lung cancer ( < 0.01), while rs212704-T appears protective ( = 0.006). The rs35829419-AA, rs385076-TC/CC, and rs775882-CT/TT genotypes were associated with various degrees of elevated risk of lung cancer (<0.02), whereas rs212704-TT was associated with a reduced risk of the disease (=0.014). Genetic models analysis showed that rs35829419, rs385076, and rs775882 was associated with an increased risk of lung cancer, while rs212704 was related to a reduced risk in all three models ( < 0.05). The four SNPs remained significant in smoker and nonsmoker subgroups ( < 0.05). However, rs35829419 was correlated with risk of adenocarcinoma and small cell lung cancer, and rs212704 was only protective for squamous cell carcinoma. The rs385076 and rs775882 were associated with all three pathological types ( < 0.01).
Besides providing candidate markers for identification of high-risk populations and early prevention of the disease, our research also provided new insight into anti-tumor strategies targeting inflammasomes and pyroptosis.
癌症发展和肿瘤免疫微环境重塑与细胞焦亡及炎性小体激活密切相关。然而，肺癌患者中细胞焦亡和炎性小体相关基因的单核苷酸多态性（SNP）信息较少。本研究旨在评估细胞焦亡相关基因（和）多态性与肺癌风险之间的关联。
采用MassARRAY平台对660例肺癌病例和660例对照的和基因的6个SNP进行基因分型。
携带rs35829419 - A、rs385076 - C和rs775882 - T等位基因的个体患肺癌风险更高（<0.01），而rs212704 - T显示出保护作用（=0.006）。rs35829419 - AA、rs385076 - TC/CC和rs775882 - CT/TT基因型与不同程度的肺癌风险升高相关（<0.02），而rs212704 - TT与疾病风险降低相关（=0.014）。遗传模型分析表明，rs35829419、rs385076和rs775882与肺癌风险增加相关，而rs212704在所有三种模型中均与风险降低相关（<0.05）。这四个SNP在吸烟者和非吸烟者亚组中仍然显著（<0.05）。然而，rs35829419与腺癌和小细胞肺癌风险相关，rs212704仅对鳞状细胞癌有保护作用。rs385076和rs775882与所有三种病理类型相关（<0.01）。
我们的研究不仅为识别高危人群和疾病的早期预防提供了候选标志物，还为针对炎性小体和细胞焦亡的抗肿瘤策略提供了新的见解。
