Feng Yanan, Li Xiaoying, Ma Qi, Zhang Shuang, Zhu Manning, Li Songxue, Fang Lei, Tian Jiawei, Sun Litao
Department of Ultrasound, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Ultrasound, Harbin Red Cross Central Hospital, Harbin, China.
Front Genet. 2021 Jul 27;12:668539. doi: 10.3389/fgene.2021.668539. eCollection 2021.
Many epidemiological studies have confirmed that gene single-nucleotide polymorphisms (SNPs) are associated with susceptibility of various cancers, but there are relatively few studies on the relationship between gene polymorphisms and the risk of cervical cancer. Therefore, we aimed to explore the potential role of gene polymorphisms and the combined effect of SNPs in the pathogenesis of cervical cancer in Han women in northern China. This case-control group includes 488 cases of cervical cancer, 684 cases of cervical precancerous lesions, and 510 healthy females. Multiplex polymerase chain reaction (PCR) combined with the next-generation sequencing method was used for the determination of gene polymorphisms (rs5498, rs3093030, and rs281432). In our study, we divide cervical cancer into two subgroups: cervical squamous cell carcinoma (CSCC) group and cervical adenocarcinoma (CAC) group. We analyzed the alleles and genotypes of all research subjects using multivariate logistic regression analysis combined with 10,000 permutation tests. In addition, we also analyzed the distribution of haplotypes of the three SNPs in cervical cancer and cervical precancerous lesions. We found that the T allele and the dominant model of rs3093030 were associated with the susceptibility of cervical cancer ( = 0.042, = 0.040, respectively). However, the significance disappeared after the Bonferroni correction for multiple testing ( > 0.05). For rs5498, its mutant gene G, the codominant model, and the dominant model could reduce the risk of CAC ( = 0.009, = 0.028, = 0.011, respectively). Significant differences remained after Bonferroni correction ( < 0.05, all). In addition, the frequency of haplotype "CTG" was significantly lower in the CAC group than in the controls. In conclusion, the study suggested that gene polymorphisms may have a potential role in the pathogenesis of cervical cancer in the northern Chinese Han population.
许多流行病学研究已证实,基因单核苷酸多态性(SNPs)与多种癌症的易感性相关,但关于基因多态性与宫颈癌风险之间关系的研究相对较少。因此,我们旨在探讨基因多态性及SNPs的联合效应在中国北方汉族女性宫颈癌发病机制中的潜在作用。本病例对照研究纳入488例宫颈癌患者、684例宫颈上皮内瘤变患者及510例健康女性。采用多重聚合酶链反应(PCR)结合二代测序方法检测基因多态性(rs5498、rs3093030和rs281432)。在本研究中,我们将宫颈癌分为两个亚组:宫颈鳞状细胞癌(CSCC)组和宫颈腺癌(CAC)组。我们采用多因素logistic回归分析结合10000次置换检验分析所有研究对象的等位基因和基因型。此外,我们还分析了这三个SNPs在宫颈癌和宫颈上皮内瘤变中的单倍型分布。我们发现,rs3093030的T等位基因和显性模型与宫颈癌易感性相关(分别为P = 0.042,P = 0.040)。然而,在进行多重检验的Bonferroni校正后,显著性消失(P>0.05)。对于rs5498,其突变基因G、共显性模型和显性模型均可降低CAC风险(分别为P = 0.009,P = 0.028,P = 0.011)。在Bonferroni校正后仍存在显著差异(均P<0.05)。此外,单倍型“CTG”在CAC组中的频率显著低于对照组。总之,该研究表明基因多态性可能在中国北方汉族人群宫颈癌发病机制中发挥潜在作用。