Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese population
Hepatocellular carcinoma associated with chronic hepatitis B virus infection seriously affects human health. Present studies suggest that genetic susceptibility plays an important role in the mechanism of cancer development. Therefore, this study focused on single nucleotide polymorphisms (SNPs) of...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1124459/full |
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| author | Ning Ma Ao Jin Yitong Sun Yiyao Jin Yucheng Sun Qian Xiao XuanYi Sha Fengxue Yu Lei Yang Wenxuan Liu Xia Gao Xiaolin Zhang Lu Li |
| author_facet | Ning Ma Ao Jin Yitong Sun Yiyao Jin Yucheng Sun Qian Xiao XuanYi Sha Fengxue Yu Lei Yang Wenxuan Liu Xia Gao Xiaolin Zhang Lu Li |
| author_sort | Ning Ma |
| collection | DOAJ |
| description | Hepatocellular carcinoma associated with chronic hepatitis B virus infection seriously affects human health. Present studies suggest that genetic susceptibility plays an important role in the mechanism of cancer development. Therefore, this study focused on single nucleotide polymorphisms (SNPs) of MMR genes associated with HBV-HCC. Five groups of participants were included in this study, which were healthy control group (HC), spontaneous clearance (SC), chronic hepatitis B group (CHB), HBV-related liver cirrhosis group (LC) and HBV-related hepatocellular carcinoma group (HBV-HCC). A total of 3128 participants met the inclusion and exclusion criteria for this study. 20 polymorphic loci on MSH2, MSH3 and MSH6 were selected for genotyping. There were four case-control studies, which were HC vs. HCC, SC vs. HCC, CHB vs. HCC and LC vs. HCC. We used Hardy-Weinberg equilibrium test, unconditional logistic regression, haplotype analysis, and gene-gene interaction for genetic analysis. Ultimately, after excluding confounding factors such as age, gender, smoking and drinking, 12 polymorphisms were found to be associated with genetic susceptibility to HCC. Haplotype analysis showed the risk haplotype GTTT (rs1805355_G, rs3776968_T, rs1428030_C, rs181747_C) was more frequent in the HCC group compared with the HC group. The GMDR analysis showed that the best interaction model was the three-factor model of MSH2-rs1981928, MSH3-rs26779 and MSH6-rs2348244 in SC vs. HCC group (P=0.001). In addition, we found multiplicative or additive interactions between genes in our selected SNPs. These findings provide new ideas to further explore the etiology and pathogenesis of HCC. We have attempted to explain the molecular mechanisms by which certain SNPs (MSH2-rs4952887, MSH3-rs26779, MSH3-rs181747 and MSH3-rs32950) affect genetic susceptibility to HCC from the perspectives of eQTL, TFBS, cell cycle and so on. We also explained the results of haplotypes and gene-gene interactions. These findings provide new ideas to further explore the etiology and pathogenesis of HCC. |
| first_indexed | 2024-04-09T21:56:23Z |
| format | Article |
| id | doaj.art-67d4532f2fdc428fa4c33b7179460aac |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T21:56:23Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-67d4532f2fdc428fa4c33b7179460aac2023-03-24T05:23:00ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-03-011310.3389/fonc.2023.11244591124459Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese populationNing Ma0Ao Jin1Yitong Sun2Yiyao Jin3Yucheng Sun4Qian Xiao5XuanYi Sha6Fengxue Yu7Lei Yang8Wenxuan Liu9Xia Gao10Xiaolin Zhang11Lu Li12Hebei Key Laboratory of Environment and Human Health, Department of Social Medicine and Health Care Management, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, School of Basic Medicine, Hebei Medical University, Shijiazhuang, ChinaThe Hebei Key Laboratory of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Environment and Human Health, Department of Social Medicine and Health Care Management, School of Public Health, Hebei Medical University, Shijiazhuang, ChinaHepatocellular carcinoma associated with chronic hepatitis B virus infection seriously affects human health. Present studies suggest that genetic susceptibility plays an important role in the mechanism of cancer development. Therefore, this study focused on single nucleotide polymorphisms (SNPs) of MMR genes associated with HBV-HCC. Five groups of participants were included in this study, which were healthy control group (HC), spontaneous clearance (SC), chronic hepatitis B group (CHB), HBV-related liver cirrhosis group (LC) and HBV-related hepatocellular carcinoma group (HBV-HCC). A total of 3128 participants met the inclusion and exclusion criteria for this study. 20 polymorphic loci on MSH2, MSH3 and MSH6 were selected for genotyping. There were four case-control studies, which were HC vs. HCC, SC vs. HCC, CHB vs. HCC and LC vs. HCC. We used Hardy-Weinberg equilibrium test, unconditional logistic regression, haplotype analysis, and gene-gene interaction for genetic analysis. Ultimately, after excluding confounding factors such as age, gender, smoking and drinking, 12 polymorphisms were found to be associated with genetic susceptibility to HCC. Haplotype analysis showed the risk haplotype GTTT (rs1805355_G, rs3776968_T, rs1428030_C, rs181747_C) was more frequent in the HCC group compared with the HC group. The GMDR analysis showed that the best interaction model was the three-factor model of MSH2-rs1981928, MSH3-rs26779 and MSH6-rs2348244 in SC vs. HCC group (P=0.001). In addition, we found multiplicative or additive interactions between genes in our selected SNPs. These findings provide new ideas to further explore the etiology and pathogenesis of HCC. We have attempted to explain the molecular mechanisms by which certain SNPs (MSH2-rs4952887, MSH3-rs26779, MSH3-rs181747 and MSH3-rs32950) affect genetic susceptibility to HCC from the perspectives of eQTL, TFBS, cell cycle and so on. We also explained the results of haplotypes and gene-gene interactions. These findings provide new ideas to further explore the etiology and pathogenesis of HCC.https://www.frontiersin.org/articles/10.3389/fonc.2023.1124459/fullHBVHCCSNPMMRhaplotypeinteraction |
| spellingShingle | Ning Ma Ao Jin Yitong Sun Yiyao Jin Yucheng Sun Qian Xiao XuanYi Sha Fengxue Yu Lei Yang Wenxuan Liu Xia Gao Xiaolin Zhang Lu Li Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese population Frontiers in Oncology HBV HCC SNP MMR haplotype interaction |
| title | Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese population |
| title_full | Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese population |
| title_fullStr | Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese population |
| title_full_unstemmed | Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese population |
| title_short | Comprehensive investigating of MMR gene in hepatocellular carcinoma with chronic hepatitis B virus infection in Han Chinese population |
| title_sort | comprehensive investigating of mmr gene in hepatocellular carcinoma with chronic hepatitis b virus infection in han chinese population |
| topic | HBV HCC SNP MMR haplotype interaction |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1124459/full |
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