Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.
Department of Gynecologic Oncology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
Int J Cancer. 2024 Jul 1;155(1):149-158. doi: 10.1002/ijc.34911. Epub 2024 Mar 6.
Human papillomavirus can be contracted by sexually active women. However, only a small proportion of these infections persist and have the potential to progress into cervical cancers, indicating a significant involvement of the immune system in cervical cancer development. Despite this, our understanding of the precise contributions of genes from different immune cell types in cervical cancers remains limited. Therefore, the primary objective of our study was to investigate the potential causal relationships between specific immune cell genes and the development of cervical cancers. By accessing expression quantitative trait loci datasets of 14 distinct immune cell types and genome wide association study of cervical cancers, we employed the summary data-based Mendelian randomization (SMR) along with multi-single nucleotide polymorphism (SNP)-based SMR to identify significant genes associated with cervical cancers. Colocalization analysis was further conducted to explore the shared genetic causality. A total of 10 genes across 11 immune cell types (26 significant gene-trait associations) were found to be associated with cervical cancers after false discovery rate correction. Notably, the ORMDL3, BRK1 and HMGN1 gene expression levels showed significant association with cervical cancer in specific immune cell types, respectively. These associations were supported by strong evidence of colocalization analyses. Our study has identified several genes in different immune cells that were associated with cervical cancer. However, further research is necessary to confirm these findings and provide more comprehensive insights into the association between these gene expressions and cervical cancer risk.
人乳头瘤病毒可通过性行为活跃的女性传播。然而,这些感染中只有一小部分持续存在并有发展为宫颈癌的潜力,这表明免疫系统在宫颈癌的发展中起着重要作用。尽管如此,我们对不同免疫细胞类型的基因在宫颈癌中的确切贡献的理解仍然有限。因此,我们研究的主要目的是研究特定免疫细胞基因与宫颈癌发展之间的潜在因果关系。通过访问 14 种不同免疫细胞类型的表达定量性状基因座数据集和宫颈癌的全基因组关联研究,我们采用基于汇总数据的孟德尔随机化(SMR)以及基于多单核苷酸多态性(SNP)的 SMR 来识别与宫颈癌相关的显著基因。进一步进行共定位分析以探索共享的遗传因果关系。在经过错误发现率校正后,在 11 种免疫细胞类型中发现了 10 个基因(26 个显著的基因-表型关联)与宫颈癌相关。值得注意的是,ORMDL3、BRK1 和 HMGN1 基因的表达水平分别与特定免疫细胞类型中的宫颈癌显著相关。这些关联得到了共定位分析的有力证据支持。我们的研究已经确定了不同免疫细胞中与宫颈癌相关的几个基因。然而,需要进一步的研究来证实这些发现,并提供更全面的见解,了解这些基因表达与宫颈癌风险之间的关联。