Familial Correlations of Onset Age of Hepatocellular Carcinoma: A Population-Based Case-Control Family Study

Liu, Li; Li, Lixia; Zhou, Shudong; Jiang, Qingwu; Chen, Sidong; Gao, Yanhui; Chen, Yue

doi:10.1371/journal.pone.0108391

Cited by 12 publications

(13 citation statements)

References 23 publications

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“…Hepatocellular carcinoma (HCC) is the fifth most frequent malignancy in the world [ 1 ]. With a mortality rate of about one million per year, it ranks the third leading cause of cancer deaths worldwide [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Relationship between TRAF6 and deterioration of HCC: an immunohistochemical and in vitro study

Luo

et al. 2016

Cancer Cell Int

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ObjectiveTo explore the relationship between tumor necrosis factor receptor-associated factor 6 (TRAF6) and the clinicopathological features in HCC as well as its biological function.MethodsTotally, 412 liver tissues were collected, including 171 hepatocellular carcinoma (HCC) and their corresponding non-tumor tissues, 37 cirrhosis and 33 normal liver tissues. The expression of TRAF6 was assessed by immunohistochemistry. Then, analysis of the correlations between TRAF6 expression and clinicopathological parameters in HCC was conducted. Furtherer, in vitro experiments on HepG2 and Hep3B cells were performed to validate the biological function of TRAF6 on HCC cells. TRAF6 siRNA was transfected into HepG2 and Hep3B cell lines and TRAF6 expression was evaluated with RT-qPCR and western blot. The assays of cell viability, proliferation, apoptosis and caspase-3/7 activity were carried out to investigate the effects of TRAF6 on HCC cells with RNA interference. Cell viability was assessed with Cell Titer-Blue kit. Cell proliferation was tested with MTS kit. Cell apoptosis was checked through morphologic detection with fluorescence microscope, as well as caspase-3/7 activity was measured with fluorogenic substrate detection.ResultsThe positive expression rate of TRAF6 protein was 49.7 % in HCC, significantly higher than that of normal liver (12.1 %), cirrhosis (21.6 %) and adjacent non-cancerous tissues (36.3 %, all P < 0.05). Upregulated TRAF6 was detected in groups with metastasis (Z = −2.058, P = 0.04) and with low micro-vessel density (MVD) expression (Z = −2.813, P = 0.005). Spearman correlation analysis further showed that the expression of TRAF6 was positively correlated with distant metastasis (r = 0.158, P = 0.039) and negatively associated with MVD (r = −0.249, P = 0.004). Besides, knock-down of TRAF6 mRNA in HCC cell lines HepG2 and Hep3B both resulted in cell viability and proliferation inhibition, also cell apoptosis induction and caspase-3/7 activity activation.ConclusionsTRAF6 may contribute to metastasis and deterioration of the HCC via influencing cell growth and apoptosis. Thus, TRAF6 might become a predictive and therapeutic biomarker for HCC.

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Section: Introductionmentioning

confidence: 99%

Relationship between TRAF6 and deterioration of HCC: an immunohistochemical and in vitro study

Luo

et al. 2016

Cancer Cell Int

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“…A familial correlation of liver cancer among FDRs predicts increasing risks of liver cancer with an addition of genetic variance functioning 16–18. Adjusting for common confounding factors like hepatitis B virus infection and alcohol intake, the familial aggregation remains significant (cross ratio [CR]=2.94, 95% CI 1.59–5.45, p =0.001) 17. Another recent study conducted in America16 showed that risks exhibited high with a family history of liver cancer (OR=4.1; 95%CI, 1.30–12.9) when potential confounding factors were controlled including age, gender, race, educational level, tobacco smoking, diabetes mellitus, alcohol consumption and HBV/HCV infection.…”

Section: Discussionmentioning

confidence: 99%

<p>Familial association of lung cancer with liver cancer in first-degree relatives</p>

Lin

et al. 2019

CMAR

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Purpose: Besides the smoking and occupational exposures, heritable factors have been proven to be a risk factor for lung cancer by several population-based studies, which would misestimate the risk of lung cancer. Patients and methods: To quantify the magnitude of the high risk of lung cancer with family history, we performed a case-based study with 1373 enrolled individuals, which may be more accurate than a population-based study. Results: Risk of lung cancer was higher in people with lung cancer family history than in the control group (OR 2.50, p <0.001). Individuals with family history of liver cancer also had a higher risk of lung cancer than the control group (OR 1.78, p =0.038) while there was no significant difference within the individuals with family history of colorectal cancer, esophageal cancer, nasopharyngeal cancer or breast cancer. Furthermore, the risk of lung cancer in the subjects with early-onset cancers (age <50 years) was higher than the later-onset cancers (age ≥50 years), especially in individuals with family history of liver cancer (OR 9.24 vs 1.39). Risk of lung cancer in females with family history of lung cancer or liver cancer was higher than in males. Conclusion: The results of this study proved that the familial aggregation of lung cancer and liver cancer manifests higher risks of lung cancer, supporting the hypothesis that lung cancer and liver cancer are attributable to common familial predisposition.

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“…Hepatocellular carcinoma (HCC) is the fifth most frequent malignancy in the world [1]. With a mortality rate of about one million per year, it ranks as the third leading cause of cancer deaths worldwide [2].…”

Section: Introductionmentioning

confidence: 99%

TRAF6 Affects RAC1 Expression and Apoptosis in SK-Hep1 Cells

Zhang¹,

Qian²,

Liu³

et al. 2018

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RAC1 is a small-molecule G protein that regulates multiple cell cycle, cytoskeletal reorganization, cell migration, and apoptosis. FADD-dependent TRAIL can promote tumor metastasis through RAC1 and PI3K, and down-regulating RAC1 expression can reduce FasL-induced apoptosis. In addition, RIP1 bound to GTP acts as an activating protein for RAC1 and is involved in cytoskeletal reorganization. TRAF6 promotes migration and metastasis by regulating the RAS pathway in tumors. Thus, it is necessary to understand the interaction between RAC1 and TRAF6 as well as FADD and RIP1. In this study, we cultured hepatoma SK-Hep1 cells in vitro, specifically blocked the necroptosis pathway with Nec-1, and silenced FADD, RIP1 and TRAF6 gene expression using RNAi technology. At the same time, the expression of RAC1 was evaluated separately using RT-PCR and Western blot. The hepatoma SK-Hep1 cells survival rate was highest when the concentration of Nec-1 was 60 μM and the concentration of Z-vad-fmk was 20 μM. And the apoptosis rate of the transfected RAC1 siRNA cells was 3.59% compared with transfected siRNA cells 10.01% which was significantly decreased (P < 0.01). RAC1 could promote the occurrence of apoptosis in SK-Hep1 cells. RAC1 expression was suppressed in both protein and gene level in SK-Hep1 cells when the TRAF6 gene was silenced, but there was no significant change in RAC1 gene and protein expression when FADD and RIP1 genes were silenced. TRAF6 affects RAC1 expression and apoptosis in SK-Hep1 cells, while the FADD and RIP1 genes do not affect the role of RAC1. The TRAF6 gene is an important target in liver cancer cells.

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Familial Correlations of Onset Age of Hepatocellular Carcinoma: A Population-Based Case-Control Family Study

Cited by 12 publications

References 23 publications

Relationship between TRAF6 and deterioration of HCC: an immunohistochemical and in vitro study

Relationship between TRAF6 and deterioration of HCC: an immunohistochemical and in vitro study

<p>Familial association of lung cancer with liver cancer in first-degree relatives</p>

TRAF6 Affects RAC1 Expression and Apoptosis in SK-Hep1 Cells

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