Žilienė Eglė, Inčiūra Arturas, Ugenskienė Rasa, Juozaitytė Elona
Institute of Oncology, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania.
Department of Genetics and Molecular Medicine, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania.
Diagnostics (Basel). 2023 Jun 7;13(12):1999. doi: 10.3390/diagnostics13121999.
Cervical cancer (CC) is often associated with human papillomavirus (HPV). Chronic inflammation has been described as one of the triggers of cancer. The immune system fights diseases, including cancer. The genetic polymorphism of pathogen recognition receptors potentially influences the infectious process, development, and disease progression. Many candidate genes SNPs have been contradictory demonstrated to be associated with cervical cancer by association studies, GWAS. gene activation can promote antitumor immunity. It can also result in immunosuppression and tumor growth. Our study aimed to investigate eight selected polymorphisms of the gene (rs10759932, rs1927906, rs11536898, rs11536865, rs10983755, rs4986790, rs4986791, rs11536897) and to determine the impact of polymorphisms in genotypes and alleles on the pathomorphological characteristics and progression in a group of 172 cervical cancer subjects with stage I-IV. Genotyping was performed by RT-PCR assay. We detected that the CA genotype and A allele of rs11536898 were significantly more frequent in patients with metastases ( = 0.026; = 0.008). The multivariate logistic regression analysis confirmed this link to be significant. The effect of rs10759932 and rs11536898 on progression-free survival (PFS) and overall survival (OS) has been identified as important. In univariate and multivariate Cox analyses, AA genotype of rs11536898 was a negative prognostic factor for PFS ( = 0.024; = 0.057, respectively) and OS ( = 0.008; = 0.042, respectively). Rs11536898 C allele predisposed for longer PFS (univariate and multivariate: = 0.025; = 0.048, respectively) and for better OS (univariate and multivariate: = 0.010; = 0.043). The worse prognostic factor of rs10759932 in a univariate and multivariate Cox analysis for survival was CC genotype: shorter PFS ( = 0.032) and increased risk of death ( = 0.048; = 0.015, respectively). The T allele of rs10759932 increased longer PFS (univariate and multivariate: = 0.048; = 0.019, respectively) and longer OS (univariate and multivariate: = 0.037; = 0.009, respectively). Our study suggests that SNPs rs10759932 and rs11536898 may have the potential to be markers contributing to the assessment of the cervical cancer prognosis. Further studies, preferably with larger groups of different ethnic backgrounds, are needed to confirm the results of the current study.
宫颈癌（CC）常与人乳头瘤病毒（HPV）相关。慢性炎症被认为是癌症的触发因素之一。免疫系统对抗包括癌症在内的疾病。病原体识别受体的基因多态性可能影响感染过程、发展及疾病进展。许多候选基因单核苷酸多态性（SNPs）经关联研究、全基因组关联研究（GWAS）已被矛盾地证明与宫颈癌相关。基因激活可促进抗肿瘤免疫。它也可导致免疫抑制和肿瘤生长。我们的研究旨在调查该基因的八个选定多态性位点（rs10759932、rs1927906、rs11536898、rs11536865、rs10983755、rs4986790、rs4986791、rs11536897），并确定这些多态性位点在基因型和等位基因方面对172例I-IV期宫颈癌患者的病理形态学特征及病情进展的影响。通过逆转录聚合酶链反应（RT-PCR）检测法进行基因分型。我们检测到rs11536898的CA基因型和A等位基因在有转移的患者中显著更常见（P = 0.026；P = 0.008）。多因素逻辑回归分析证实这种关联具有显著性。已确定rs10759932和rs11536898对无进展生存期（PFS）和总生存期（OS）的影响很重要。在单因素和多因素Cox分析中，rs11536898的AA基因型是PFS的负性预后因素（分别为P = 0.024；P = 0.057）和OS的负性预后因素（分别为P = 0.008；P = 0.042）。rs11536898的C等位基因有利于更长的PFS（单因素和多因素分析中：分别为P = 0.025；P = 0.048）和更好的OS（单因素和多因素分析中：分别为P = 0.010；P = 0.043）。在单因素和多因素Cox生存分析中，rs10759932的CC基因型是更差的预后因素：PFS更短（P = 0.032）且死亡风险增加（分别为P = 0.048；P = 0.015）。rs10759932的T等位基因使PFS更长（单因素和多因素分析中：分别为P = 0.048；P = 0.019）且OS更长（单因素和多因素分析中：分别为P = 0.037；P = 0.009）。我们的研究表明，SNPs rs10759932和rs11536898可能有潜力成为有助于评估宫颈癌预后的标志物。需要进一步的研究，最好是纳入更大规模不同种族背景人群的研究，以证实本研究结果。
