Abstract
BackgroundPrevious evidence has shown that the FOXP3 gene was involved in the pathogenesis of several tumors; however, the correlation between single nucleotide polymorphisms (SNPs) in the FOXP3 gene and the susceptibility to hepatitis B-related hepatocellular carcinoma (HCC) remains unclear.MethodsWe analyzed two SNPs in the FOXP3 gene, rs2280883 and rs3761549, in 392 patients with HCC, 344 patients with chronic hepatitis B (CHB) and 372 matched healthy controls. Genotyping was performed by MALDI-TOF Mass Spectrometry for all donors.ResultsCompared to healthy controls, HCC patients had higher frequencies of the TT genotype (79.6%) at rs2280883 and the CC genotype (77.6%) at rs3761549 of the FOXP3 gene; CHB patients also had higher frequencies of the TT genotype (74.1%) at rs2280883 and the CC genotype (74.6%) at rs3761549. There were no significant differences in the distribution of FOXP3 genotypes between CHB donors and HCC donors. The TT genotype at rs2280883 was more frequent in patients with HCC than healthy donors (P = 0.01), but no significant difference was observed in this genotype between CHB and healthy donors (P = 0.479). C allele frequency at rs3761549 was higher in HCC patients than healthy donors (P = 0.03), but distribution of this allele was not significantly different between CHB patients and healthy donors (P = 0.11). Stratified analysis showed that the CC genotype at rs3761549 was significantly associated with a high incidence of portal vein tumor thrombus (P = 0.02) and that the TT/CT genotype at rs3761549 was significantly associated with an increased rate of tumor recurrence in HCC patients (P = 0.001).ConclusionsOur results suggested that the FOXP3 gene polymorphisms at rs2280883 and rs3761549 may be associated with hepatitis B-related HCC. At rs3761549, the CC genotype and the TT/CT genotype were associated with a high incidence of portal vein tumor thrombus and tumor recurrence, respectively.
Highlights
Previous evidence has shown that the FOXP3 gene was involved in the pathogenesis of several tumors; the correlation between single nucleotide polymorphisms (SNPs) in the FOXP3 gene and the susceptibility to hepatitis B-related hepatocellular carcinoma (HCC) remains unclear
Statistical analysis Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), γ-Glutamyl transpeptidase (GGT), total bilirubin (TBIL) and AFP levels were reported as the mean ± standard deviation, and the distributions of these variables were compared by Kruskal-Wallis tests; AFP values between HCC and chronic hepatitis B (CHB) donors were compared by the Mann–Whitney U test
The analysis of FOXP3 SNPs allele frequency in all donors In Table 3, there was no significant difference in the distribution of C and T alleles at rs2280883 of FOXP3 between HCC and healthy donors (P = 0.20), and the frequencies of C and T alleles at rs2280883 were similar in CHB donors and healthy donors (P = 0.54)
Summary
The distribution of demographic and clinical characteristics of all donors As shown in Table 1, there were no significant differences in the age, AST, ALT, GGT, and TBIL levels between either HCC or CHB groups and the healthy group (all P > 0.05). The distribution of demographic and clinical characteristics of all donors there were no significant differences in the age, AST, ALT, GGT, and TBIL levels between either HCC or CHB groups and the healthy group (all P > 0.05). The AFP level and the frequency of cirrhosis were significantly higher in the HCC group than in the CHB group. The distributions of gender and alcohol abuse showed that male alcohol-abusing donors accounted for the majority of the HCC, CHB and healthy donors. The C allele frequency at rs3761549 was higher in HCC donors than in healthy donors (OR 1.32; 95% CI 1.03-1.70; P = 0.03), but there was no significant difference in the distribution of C and T alleles at rs3761549 between CHB patients and healthy donors (P = 0.11).
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