背景:宫颈癌是全球女性中第四常见的癌症。全基因组关联研究揭示了宫颈癌风险的多个易感基因及其多态性。因此,我们旨在研究中国东北汉族人群CD40基因单核苷酸多态性(SNPs)与宫颈鳞状细胞癌(CSCC)易感性之间的相关性.
方法:通过多重聚合酶链反应(PCR)结合下一代测序方法,对421例CSCC患者CD40基因的三个SNP(rs1800686,rs3765459和rs4810485)进行分析。594例高度鳞状上皮内病变(HSIL),504名健康女性。多因素logistic回归分析CD40基因多态性与CSCC,或者HSIL.
结果:我们的研究结果表明,与GG基因型和AGGG基因型相比,rs1800686的AA基因型对CSCC具有保护作用(AA与GG:p=0.0389和AAvs.AG+GG:p=0.0280,分别)。FDR校正后,结果仍有统计学意义(分别为p=0.0389和p=0.0389).同样,rs3765459在显性和隐性模型中显示CSCC的风险关联降低(AA与GG:p=0.0286和AAvs.AG+GG:分别为p=0.0222)。FDR校正后仍存在显着差异(分别为p=0.0286和p=0.0286)。然而,Bonferroni校正后,这些差异不再显著.此外,rs4810485多态性的基因型与CSCC患者的产次相关.rs3765459多态性的基因型与CSCC患者的D-二聚体显著相关。CD40基因的3个SNPs基因型与HSIL患者的鳞状细胞癌抗原(SCC)亲密相干。
结论:CD40基因可能在CSCC的发生发展中起作用。
BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical cancer risk. Therefore, we aimed to investigate the correlation between single nucleotide polymorphisms (SNPs) of the CD40 gene and susceptibility to cervical squamous cell carcinoma (CSCC) in a population from the northeastern Han Chinese population.
METHODS: The three SNPs (rs1800686, rs3765459, and rs4810485) of the CD40 gene were analyzed by multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods in 421 patients with CSCC, 594 patients with high-grade squamous intraepithelial lesions (HSIL), and 504 healthy females. Multivariate logistic regression analysis was used to analyze the potential relationship between CD40 gene polymorphisms and CSCC, or HSIL.
RESULTS: Our research results showed the AA genotype of rs1800686 had a protective effect on CSCC in comparison to the GG genotype and AG+GG genotypes (AA vs. GG: p = 0.0389 and AA vs. AG+GG: p = 0.0280, respectively). After FDR correction, the results were still statistically significant (p = 0.0389 and p = 0.0389, respectively). Similarly, rs3765459 showed a reduced risk association for CSCC in the codominant and recessive models (AA vs. GG: p = 0.0286 and AA vs. AG+GG: p = 0.0222, respectively). Significant differences remained after FDR correction (p = 0.0286 and p = 0.0286, respectively). However, these differences were no longer significant after the Bonferroni correction. In addition, the genotypes for the rs4810485 polymorphisms were associated with parity of the patients with CSCC. The genotypes for the rs3765459 polymorphisms were significantly correlated with the D-dimer of the patients with CSCC. The 3 SNPs genotypes of the CD40 gene were closely related to the squamous cell carcinoma antigen (SCC) of the patients with HSIL.
CONCLUSIONS: The CD40 gene may play a role in the occurrence and development of CSCC.