背景:COX/PGE2通路广泛参与肿瘤的发展和T细胞等肿瘤免疫细胞的调节,NK细胞和DC。然而,关于肺癌患者COX/PGE2通路相关基因的单核苷酸多态性(SNP)的信息很少.
方法:在包括600例肺癌病例和600例对照的病例对照队列中,使用MassARRAY平台对PTGS2、PTGER2和PTGIS基因的7个SNP进行基因分型。
结果:PTGS2-rs4648298、PTGS2-rs2745557、PTGER2-rs2075797和PTGIS-rs6125671的次要等位基因均为导致不同程度肺癌风险升高的风险等位基因(p<0.001)。rs4648298-TC/CC,rs2745557-GA/AA,rs2075797-CG/GG和rs6125671-TC/CC基因型与肺癌风险升高显著相关(p<0.0001)。此外,遗传模型结果表明,PTGS2-rs4648298与4.91-,占主导地位的肺癌风险增加6.90-和4.21倍,隐性和对数累加模型,分别(p<0.0001)。同样,PTGS2-rs2745557,PTGER2-rs2075797和PTGIS-rs6125671也与三种遗传模型下的疾病风险升高有关(p<0.001)。此外,基于吸烟状况和病理类型的分层分析表明,这四个SNP与吸烟者和非吸烟者以及所有三种病理类型的肺癌风险相关。包括腺癌,鳞状细胞癌,和小细胞肺癌(p<0.014)。
结论:这些结果有助于更好地理解肺癌的发病机制,并为疾病的早期发现和个性化治疗提供新的线索。
BACKGROUND: The COX/PGE2 pathway is widely involved in the development of tumors and the regulation of tumor immune cells such as T cells, NK cells and DCs. However, little information is available on the single nucleotide polymorphisms (SNPs) of COX/PGE2 pathway-related genes in patients with lung cancer.
METHODS: Seven SNPs of the PTGS2, PTGER2 and PTGIS genes were genotyped in a
case-control cohort including 600 lung cancer cases and 600 controls using the MassARRAY platform.
RESULTS: The minor alleles of PTGS2-rs4648298, PTGS2-rs2745557, PTGER2-rs2075797 and PTGIS-rs6125671 were all risk alleles that led to a different degree of elevated lung cancer risk (p < 0.001). The rs4648298-TC/CC, rs2745557-GA/AA, rs2075797-CG/GG and rs6125671-TC/CC genotypes were markedly associated with an elevated risk of lung cancer (p < 0.0001). Moreover, genetic model results showed that PTGS2-rs4648298 was correlated with a 4.91-, 6.90- and 4.21-fold increased risk of lung cancer under dominant, recessive and log-additive models, respectively (p < 0.0001). Similarly, PTGS2-rs2745557, PTGER2-rs2075797 and PTGIS-rs6125671 were also related to an elevated risk of the disease under the three genetic models (p < 0.001). In addition, stratification analysis based on smoking status and pathological types showed that these four SNPs were associated with the risk of lung cancer in both smokers and nonsmokers and in all three pathological types, including adenocarcinoma, squamous cell carcinoma, and small cell lung cancer (p < 0.014).
CONCLUSIONS: These results contribute to a better understanding of the pathogenesis of lung cancer and provide new clues for the early detection and personalized treatment of the disease.