Genetic association study of intron variants in the forkhead box protein P3 gene in Chinese patients diagnosed with cervical cancer

• Published in: Journal of cellular and molecular medicine Vol. 26; no. 9; pp. 2658 - 2672
• Main Authors: Shi, Feng, Pang, Xiao‐xia, Li, Guang‐jing, Chen, Zhi‐hong, Dong, Ming‐you, Wang, Jun‐li
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2022; John Wiley and Sons Inc
• Subjects: Algorithms; Alleles; Case-Control Studies; Cervical cancer; Cervix; China; Enzymes; Female; Forkhead Box Protein O3 - genetics; forkhead box protein P3; Forkhead protein; Forkhead Transcription Factors - genetics; Foxp3 protein; Gene expression; Genetic Association Studies; Genetic Predisposition to Disease; genetic variants; Genotype; Genotyping; Haplotypes; Hospitals; Human papillomavirus; Humans; immune infiltration; Infections; Infiltration; Introns - genetics; Lesions; Medical prognosis; Mutation; Original; Papillomavirus Infections - genetics; Pathogenesis; Polymorphism, Single Nucleotide - genetics; Prognosis; Proteins; RNA polymerase; Single-nucleotide polymorphism; Uterine Cervical Neoplasms - genetics; Womens health; China; India; genetic variants; forkhead box protein P3; immune infiltration; cervical cancer; human papillomavirus
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.17276

The aim of this study was to investigate the effects of forkhead box protein P3 (FOXP3) intron single nucleotide variants (SNVs) in high‐risk human papilloma virus (HR‐HPV) infection and cervical cancer (CC) malignant lesions. We performed FOXP3 genotyping in 350 patients with CC and 350 healthy controls using the ImLDR multiple single nucleotide polymorphism genotyping technology. The heterozygous mutation TC in rs2294021 decreased the risk of HR‐HPV infection and CC malignant lesions (TC vs. TT: OR = 0.71, 95% CI = 0.51–0.99); the dominant model TC+CC and allele C in rs2294021 decreased the risk of CC malignant lesions (TC+CC vs. TT: OR = 0.69, 95% CI = 0.50–0.95; C vs. T: OR = 0.78, 95% CI = 0.63–0.97). The heterozygous mutation GA, dominant model GA+AA and allele A in rs3761549 also decreased the risk of HR‐HPV infection and CC malignant lesions (GA vs. GG: OR = 0.70, 95% CI = 0.51–0.96; GA+AA vs. GG: OR = 0.69, 95% CI = 0.51–0.94; A vs. G: OR = 0.75, 95% CI = 0.58–0.96). Patients with CC and HR‐HPV infection carrying rs2294021 TC and rs3761549 GA had lower expression of FOXP3 protein. Haplotype analysis revealed that T‐C‐A decreased the risk of HR‐HPV infection. Furthermore, we found a significant association between immune cells infiltration and prognosis in patients with CC. Our findings demonstrated that rs2294021 and rs3761549 variants may protect against HR‐HPV and CC malignant lesions by downregulating FOXP3 and that FOXP3 was associated with immune cells infiltration, which affected the prognosis of CC.