Association Between the c.3751G&gt;A Genetic Variant of MDR1 and Hepatocellular Carcinoma Risk in a Chinese Han Population

Li, Xiaofei; He, Hongbin; Zhu, Yanshuang; He, Jinke; Ye, Wei-Wei; Chen, Yongxin; Lou, Lianqing

doi:10.7314/apjcp.2013.14.9.5361

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…Studies have demonstrated that chronic HBV carriers with a family history of HCC have a two-fold risk for HCC over those without any family history (Yu et al, 2000), which suggested that genetic susceptibility for HBV-related HCC is a strong component of this disease. Furthermore, it is common knowledge that single nucleotide polymorphisms (SNPs) in immune response and tumorigenesis related genes, such as XPD, XRCC1,MDR1,EGF,TP53, and GSTT1 might affect the host immune response to virus infection as well as provide crucial genetic markers for determining the stages of HCC development (Chen et al, 2012;Guo et al, 2012;Ren et al, 2012;Li et al, 2012Li et al, , 2013Thongbai et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Relationship between HLA-DP gene polymorphisms and the risk of hepatocellular carcinoma: a meta-analysis

Zhang

Zheng

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The association between the HLA-DP single nucleotide polymorphisms (SNPs) rs3077 and rs9277535 and hepatocellular carcinoma (HCC) has been reported, but results have been inconclusive and controversial. Therefore, to investigate the relationship between these HLA-DP SNPs and HCC susceptibility, a meta-analysis of studies published before January 2014 was carried out using the PubMed and Google Scholar databases. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated for HLA-DP alleles, and for co-dominant, dominant, and recessive genotype models of each SNP, based on fixed-or randomeffects models. A total of nine studies from six published articles were included. The association study between rs3077 and HCC susceptibility was performed in four independent comparisons that contained 1871 cases with hepatitis B virus (HBV)-related HCC and 3207 carriers with (2015) persistent HBV. Association between rs9277535 and HCC susceptibility was examined in five separate comparisons that contained 2017 cases and 3930 carriers. Our analysis indicated a significant association of rs3077 and rs9277535 with HCC susceptibility, suggesting that rs3077 might act beneficially against HCC susceptibility (A vs G: OR = 0.884, 95%CI = 0.803-0.973, P = 0.012; GA vs GG: OR = 0.842, 95%CI = 0.733-0.967, P = 0.015; AA+GA vs GG: OR = 0.848, 95%CI = 0.744-0.968, P = 0.014), and that rs9277535 might promote HCC susceptibility (AA vs GA: OR = 1.202, 95%CI = 1.011-1.428, P = 0.037). This study suggested that HLA-DP rs3077 and rs9277535 polymorphisms are associated with HCC susceptibility in the Asian population.

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Section: Introductionmentioning

confidence: 99%

Relationship between HLA-DP gene polymorphisms and the risk of hepatocellular carcinoma: a meta-analysis

Zhang

Zheng

et al. 2015

Genet. Mol. Res.

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“…The functional significance of single nucleotide polymorphisms (SNPs) of ABCB1 (PGP/MDR1), ABCC1 (MRP1), ABCC2 (MRP2), and ABCG2 (BCRP) in in vitro systems, in vivo, and drug disposition was previously reviewed, as well as on the clinical outcome [34,35]. Various SNPs of the ABCB1 (SNPs 335T>C, 3073A>C, 3751G>A, and 4125A>C) had also been associated with the risk of occurrence of HCC in Chinese populations [36][37][38].…”

Section: Drug Efflux: Abc Transporters Familymentioning

confidence: 99%

Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity

Cabral

Tiribelli

Sukowati

2020

Cancers

117

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Despite advances in biomedicine, the incidence and the mortality of hepatocellular carcinoma (HCC) remain high. The majority of HCC cases are diagnosed in later stages leading to the less than optimal outcome of the treatments. Molecular targeted therapy with sorafenib, a dual-target inhibitor targeting the serine-threonine kinase Raf and the tyrosine kinases VEGFR/PDGFR, is at present the main treatment for advanced-stage HCC, either in a single or combinatory regimen. However, it was observed in a large number of patients that its effectiveness is hampered by drug resistance. HCC is highly heterogeneous, within the tumor and among individuals, and this influences disease progression, classification, prognosis, and naturally cellular susceptibility to drug resistance. This review aims to provide an insight on how HCC heterogeneity influences the different primary mechanisms of chemoresistance against sorafenib including reduced drug intake, enhanced drug efflux, intracellular drug metabolism, alteration of molecular targets, activation/inactivation of signaling pathways, changes in the DNA repair machinery, and negative balance between apoptosis and survival of the cancer cells. The diverse variants, mutations, and polymorphisms in molecules and their association with drug response can be a helpful tool in treatment decision making. Accordingly, the existence of heterogeneous biomarkers in the tumor must be considered to strengthen multi-target strategies in patient-tailored treatment.

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“…A recent study showed that ABCB1, encoding for multidrug resistance protein 1 (MDR1), genetic variant rs2032582 (3435 C > T) is associated with the lowest sorafenib plasma levels in HCC patients and hence, is related to sorafenib resistance [35]. Furthermore, an interesting finding was elaborated by a study conducted on the Chinese population, in which SNPs in ABCB1 (335T > C, 3073A > C, 3751G > A, and 4125A > C) were associated with the risk of HCC development [53][54][55].…”

Section: Abc Transportersmentioning

confidence: 99%

Genetic Heterogeneity, Therapeutic Hurdle Confronting Sorafenib and Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Atwa

Odenthal

Tayebi

2021

Cancers

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Despite the latest advances in hepatocellular carcinoma (HCC) screening and treatment modalities, HCC is still representing a global burden. Most HCC patients present at later stages to an extent that conventional curative options are ineffective. Hence, systemic therapy represented by the tyrosine kinase inhibitor, sorafenib, in the first-line setting is the main treatment modality for advanced-stage HCC. However, in the two groundbreaking phase III clinical trials, the SHARP and Asia-Pacific trials, sorafenib has demonstrated a modest prolongation of overall survival in almost 30% of HCC patients. As HCC develops in an immune-rich milieu, particular attention has been placed on immune checkpoint inhibitors (ICIs) as a novel therapeutic modality for HCC. Yet, HCC therapy is hampered by the resistance to chemotherapeutic drugs and the subsequent tumor recurrence. HCC is characterized by substantial genomic heterogeneity that has an impact on cellular response to the applied therapy. And hence, this review aims at giving an insight into the therapeutic impact and the different mechanisms of resistance to sorafenib and ICIs as well as, discussing the genomic heterogeneity associated with such mechanisms.

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Association Between the c.3751G>A Genetic Variant of MDR1 and Hepatocellular Carcinoma Risk in a Chinese Han Population

Cited by 6 publications

References 36 publications

Relationship between HLA-DP gene polymorphisms and the risk of hepatocellular carcinoma: a meta-analysis

Relationship between HLA-DP gene polymorphisms and the risk of hepatocellular carcinoma: a meta-analysis

Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity

Genetic Heterogeneity, Therapeutic Hurdle Confronting Sorafenib and Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

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