Pyroptosis and Inflammasome-Related Genes-NLRP3, NLRC4 and NLRP7 Polymorphisms Were Associated with Risk of Lung Cancer.

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics & Personalized Medicine Pub Date : 2023-01-01 DOI:10.2147/PGPM.S424326

Xin Jing, Yuhui Yun, Xiang Ji, Ende Yang, Pei Li

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引用次数: 0

Abstract

Background: 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 (NLRP3, NLRC4, and NLRP7) polymorphisms and the risk of lung cancer.

Methods: The MassARRAY platform was used to genotype six SNPs of the NLRP3, NLRC4, and NLRP7 genes in 660 lung cancer cases and 660 controls.

Results: Individuals with rs35829419-A, rs385076-C, and rs775882-T alleles exhibited a higher risk of lung cancer (p < 0.01), while rs212704-T appears protective (p = 0.006). The rs35829419-AA, rs385076-TC/CC, and rs775882-CT/TT genotypes were associated with various degrees of elevated risk of lung cancer (p<0.02), whereas rs212704-TT was associated with a reduced risk of the disease (p=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 (p < 0.05). The four SNPs remained significant in smoker and nonsmoker subgroups (p < 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 (p < 0.01).

Conclusion: 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.

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焦亡和炎性小体相关基因nlrp3、NLRC4和NLRP7多态性与肺癌风险相关

背景:肿瘤的发展和肿瘤免疫微环境重塑与焦亡和炎性体活化密切相关。然而，关于肺癌患者焦亡和炎性小体相关基因的单核苷酸多态性(snp)的信息很少。本研究的目的是评估热作用相关基因(NLRP3、NLRC4和NLRP7)多态性与肺癌风险的关系。方法:利用MassARRAY平台对660例肺癌患者和660例对照者的NLRP3、NLRC4和NLRP7基因的6个snp进行基因分型。结果:携带rs35829419-A、rs385076-C和rs775882-T等位基因的个体患肺癌的风险较高(p < 0.01)，而携带rs212704-T等位基因的个体具有保护作用(p = 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(pp=0.014)。遗传模型分析显示，rs35829419、rs385076和rs775882与肺癌风险增加相关，而rs212704与肺癌风险降低相关(p < 0.05)。这4个snp在吸烟者和非吸烟者亚组中仍然显著(p < 0.05)。然而，rs35829419与腺癌和小细胞肺癌的风险相关，rs212704仅对鳞状细胞癌有保护作用。rs385076和rs775882与3种病理类型均相关(p < 0.01)。结论:我们的研究除了为高危人群的识别和疾病的早期预防提供候选标志物外，还为针对炎症小体和焦亡的抗肿瘤策略提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

3.30

自引率

5.30%

发文量

110

审稿时长

16 weeks

期刊介绍： Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.