Single Nucleotide Polymorphisms ofCBX4andCBX7Decrease the Risk of Hepatocellular Carcinoma

Background. The chromobox (CBX) proteins CBX2, CBX4, CBX6, CBX7, and CBX8, also known as Polycomb (Pc) proteins, are canonical components of the Polycomb repressive complex 1 (PRC1). Abundant evidence indicates that abnormal expression of Pc proteins is associated with a variety of tumors, but their role in the pathogenesis of hepatocellular carcinoma (HCC) has not been fully elucidated. In the present study, we performed a case-control study to investigate the relationship between single nucleotide polymorphisms (SNPs) ofCBXgenes and HCC.Methods. Nine SNPs onCBXgenes (rs7217395, rs2036316 ofCBX2; rs3764374, rs1285251, rs2289728 ofCBX4; rs7292074 ofCBX6; and rs710190, rs139394, rs5750753 ofCBX7) were screened and genotyped using MassARRAY technology in 334 HCC cases and 321 controls. The association between SNPs and their corresponding gene expressions was analyzed through bioinformatics methods using the Ensembl database and Blood eQTL browser online tools.Results. The results indicated that rs2289728 (G>A) ofCBX4(P= 0.03, OR = 0.56, 95% CI: 0.33-0.94) and rs139394 (C>A) ofCBX7(P= 0.02, OR = 0.55, 95% CI: 0.33-0.90) decreased the risk of HCC. Interaction between rs2036316 and HBsAg increased the risk of HCC (P= 0.02, OR = 6.88, 95% CI: 5.20-9.11), whereas SNP-SNP interaction between rs710190 and rs139394 reduced the risk of HCC (P= 0.03, OR = 0.33, 95% CI: 0.12-0.91). Gene expression analyses showed that the rs2289728 A allele and the rs139394 A allele significantly reducedCBX4andCBX7expression, respectively.Conclusion. Our findings suggest thatCBX4rs2289728 andCBX7rs139394 are protective SNPs against HCC. The two SNPs may reduce the risk of HCC while suppressing the expression ofCBX4andCBX7.

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Single‐nucleotide polymorphisms in the coding region of a disintegrin and metalloproteinase with thrombospondin motifs 4 and hepatocellular carcinoma: A retrospective case‐control study

Cancer Medicine ◽

10.1002/cam4.2646 ◽

2019 ◽

Vol 8 (18) ◽

pp. 7869-7880

Author(s):

Xing‐Zhizi Wang ◽

Wei‐Zhong Tang ◽

Qun‐Ying Su ◽

Jin‐Guang Yao ◽

Xiao‐Ying Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Single Nucleotide Polymorphisms ◽

Case Control Study ◽

Case Control ◽

Nucleotide Polymorphisms ◽

Coding Region ◽

Retrospective Case ◽

Single Nucleotide ◽

A Disintegrin And Metalloproteinase ◽

Control Study

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A case-control study on the relationship between miRNAs single nucleotide polymorphisms and sepsis risk

Medicine ◽

10.1097/md.0000000000016744 ◽

2019 ◽

Vol 98 (33) ◽

pp. e16744 ◽

Cited By ~ 1

Author(s):

Yan Zhang ◽

Min Li ◽

Lanying Bao ◽

Pengfei Hu

Keyword(s):

Single Nucleotide Polymorphisms ◽

Case Control Study ◽

Case Control ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Sepsis Risk ◽

The Relationship ◽

Control Study

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The Relationship Between Single-Nucleotide Polymorphisms, the Expression of DNA Damage Response Genes, and Hepatocellular Carcinoma in a Polish Population

DNA and Cell Biology ◽

10.1089/dna.2017.3664 ◽

2017 ◽

Vol 36 (8) ◽

pp. 693-708 ◽

Cited By ~ 8

Author(s):

Renata Krupa ◽

Piotr Czarny ◽

Paulina Wigner ◽

Joanna Wozny ◽

Maciej Jablkowski ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Dna Damage ◽

Single Nucleotide Polymorphisms ◽

Dna Damage Response ◽

Polish Population ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Damage Response ◽

The Relationship

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CD44, IL-33, and ST2 Gene Polymorphisms on Hepatocellular Carcinoma Susceptibility in the Chinese Population

BioMed Research International ◽

10.1155/2020/2918517 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Xiaolan Pan ◽

Meiqin Li ◽

Lei Huang ◽

Dan Mo ◽

Yihua Liang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Single Nucleotide Polymorphisms ◽

Chinese Population ◽

Haplotype Analysis ◽

Control Group ◽

Case Group ◽

Nucleotide Polymorphisms ◽

Cancer Stemness ◽

Single Nucleotide ◽

The Relationship

The interleukin- (IL-) 33/ST2 axis plays a pivotal role in tumorigenesis through influencing cancer stemness and other mechanisms. CD44 is one of the critical markers of hepatocellular carcinoma (HCC) among the cancer stem cells (CSCs). There is still a lack of CD44 gene single-nucleotide polymorphisms (SNPs) combined with IL-33/ST2 pathway single-nucleotide polymorphisms in HCC susceptibility analysis literature, although CD44 and IL-33/ST2 have been reported separately in human cancers. This study is aimed at investigating the relationship between CD44, IL-33, and ST2 SNPs and HCC susceptibility and clinicopathological features. We analyzed 565 HCC patients and 561 healthy controls in the Chinese population. The genes for CD44rs187115A>G, IL-33 rs1929992A>G, and ST2 rs3821204G>C were typed using the SNaPshot method. We found that the distribution frequencies of CD44 and ST2 alleles and genotypes in both the HCC case group and the control group were statistically significant ( p < 0.05 ). The results showed that individuals carrying at least one G allele of the CD44 rs187115 gene were at a higher risk than the AA genotype carriers ( p = 0.007 , odds ratio OR = 1.429 , 95% confidence interval (CI): 1.102–1.854). Similarly, individuals with at least one C allele of ST2 rs3821204 had a higher risk of HCC than those with GG genes ( p ≤ 0.001 , OR = 1.647 , 95% CI: 1.296-2.093). Combining the haplotype analysis of the 3 loci suggested that CD44 rs187115, IL-33 rs1929992, and ST2 rs3821204 are associated with the risk of HCC and could potentially serve as useful genetic markers for HCC in some populations of China.

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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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