Single nucleotide polymorphisms in telomere length-related genes are associated with hepatocellular carcinoma risk in the Chinese Han population

Background: Single nucleotide polymorphisms (SNPs) in telomere-related genes are associated with a high risk of hepatocellular carcinoma (HCC). In this study, we investigated the SNPs of telomere length-related genes and their correlation with HCC risk in the Chinese Han population. Materials and methods: A total of 473 HCC patients and 564 healthy volunteers were recruited. Overall, 42 SNPs distributed in telomere-related genes were selected and identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: We found rs6713088 (OR = 1.27, 95% CI = 1.07–1.52, p = 0.007), rs843711 (OR = 1.29, 95% CI = 1.09–1.54, p = 0.004) and rs843706 (OR = 1.30, 95% CI = 1.09–1.55, p = 0.003) in the ACYP2 gene, rs10936599 (OR = 1.21, 95% CI = 1.02–1.44, p = 0.032) in the TERC gene and rs7708392 (OR = 1.24, 95% CI = 1.00–1.52, p = 0.042) in the TNIP1 gene were associated with high HCC risk (OR > 1). In contrast, rs1682111 (OR = 0.77, 95% CI = 0.64–0.94, p = 0.008) in the ACYP2 gene, rs2320615 (OR = 0.79, 95% CI = 0.64–0.99, p = 0.038) in the NAF1 gene, rs10069690 (OR = 0.75, 95% CI = 0.59–0.96, p = 0.021) and rs2242652 (OR = 0.70, 95% CI = 0.55–0.90, p = 0.004) in the TERT gene were associated with low HCC risk (OR < 1). Based on genotype frequency distributions, rs6713088, rs843645, rs843711 and rs843706 located in the ACYP2 gene as well as rs10936599 in the TERC gene were associated with a high incidence of HCC ( p < 0.05). In addition, SNPs in these genes could form a linkage imbalance haplotype. Specifically, the haploid ‘GC’ formed by rs10069690 and rs2242652 within the TERT gene increased the risk of HCC ( p < 0.05). Conclusion: SNPs in ACYP2, TERC, TERT and other genes were correlated with HCC risk in the Chinese Han population. These data may provide new insights into early diagnosis and screening of HCC.

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A new discovery of STAT4 single nucleotide polymorphisms associated with hepatocellular carcinoma risk in Chinese Han population: a case-control study

Bioscience Reports ◽

10.1042/bsr20210124 ◽

2021 ◽

Author(s):

Xu Chao ◽

Jieqiong Wu ◽

Wei Zhang ◽

Xuesong Feng ◽

Luyan Zhao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Single Nucleotide Polymorphisms ◽

Case Control Study ◽

Case Control ◽

Chinese Han Population ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

Han Population ◽

Control Study

Background: Hepatocellular carcinoma (HCC) is a common fatal malignant tumor worldwide. STAT4 is HCC susceptibility gene identified by genome-wide association study. The purpose of this study was to determine the association between four candidate single nucleotide polymorphisms (SNPs) in STAT4 genes and HCC risk in Chinese Han population. Methods: A case-control study was conducted to assess the association between STAT4 SNPs and HCC risk in 1011 Chinese Han population. Agena MassARRAY was used to genotype SNPs. The association between SNPs and HCC susceptibility under different genetic models was evaluated by logistic regression analysis. Multifactorial dimension reduction (MDR) analyzed the interaction of ‘SNP-SNP’ in HCC risk. The difference of clinical characteristics between different genotypes was completed by ANOVA. Results: The results showed that STAT4 rs11889341 was significantly associated with HCC risk under multiple genetic models (homozygote: OR = 0.60, p = 0.033; recessive: OR = 0.63, p = 0.028; log-additive: OR = 0.83, p = 0.032). The results of subgroup analysis showed that STAT4 rs11889341 is significantly associated with HCC risk with participants who were > 55 years, male or smoking. Both STAT4 rs7574865 and rs10174238 were significantly associated with HCC risk among participants who were > 55 years old, smoking or drinking. STAT4 haplotype (Trs11889341Trs7574865) could reduce the risk of HCC. In addition, rs11889341 and rs7574865 were significantly associated with the level of serum ferritin. Conclusion: STAT4 rs11889341, rs7574865 or rs10174238 is potentially associated with HCC risk in Chinese Han population. In particular, rs11889341 showed outstanding association with HCC risk.

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