Genetic polymorphism ofNFKB1andNFKBIAgenes and liver cancer risk: a nested case–control study in Shanghai, China

Abstract

ObjectivesGenetic variations of nuclear factor-κB (NF-κB) signalling pathway were found to be associated with inflammatory diseases and several malignancies. However, little is known about NF-κB pathway gene polymorphisms and susceptibility of liver cancer. The aim of this study was to investigate whether genetic variants of NFKB1 and NFKBIA were associated with risk of liver cancer in a Chinese population.DesignThe study was designed as a nested case–control study within two prospective cohorts (the Shanghai Women's Health Study, SWHS, 1996–2000 and the Shanghai Men's Health Study, SMHS, 2002–2006).SettingsThis population-based study was conducted in urban Shanghai, China.ParticipantsA total of 217 incident liver cancer cases diagnosed through 31 December 2009 and 427 healthy controls matched by sex, age at baseline (±2 years) and date (±30 days) of sample collection were included in the study.Primary and secondary outcome measuresGenetic polymorphisms of NFKB1 and NFKBIA were determined blindly by TaqMan single-nucleotide polymorphism (SNP) genotyping assay. OR and its 95% CIs were estimated by an unconditional logistic regression model to measure the association between selected SNPs and the risk of liver cancer.ResultsAfter adjusted for potential confounding factors, rs28362491 ins/del or del/del genotypes were associated with higher risk of liver cancer with an adjusted OR 1.54 (95% CI 1.04 to 2.28). rs230496 AG and GG genotypes were also noted with higher risk of liver cancer with an adjusted OR 1.53 (95% CI 1.03 to 2.26). Haplotype analysis indicated that carriers of the NFKB1 GA and AA (rs230525-rs230530) haplotypes had higher risk of liver cancer under an additive model. No association was observed between NFKBIA variants and risk of live cancer.ConclusionsOur results suggest that genetic variants of NFKB1 influence liver cancer susceptibility in Chinese population, although replication in other studies is needed.

Exogenous hydrogen sulfide exerts proliferation/anti-apoptosis/angiogenesis/migration effects via amplifying the activation of NF-κB pathway in PLC/PRF/5 hepatoma cells

“…Treatment of PLC/PRF/5 hepatoma cells with 500 µmol/l NaHS for 24 h markedly diminished cell apoptosis, and decreased the expression level of caspase-3, an apoptotic factor. The above result was consistent with previous reports (13)(14)(15)(16)(17)(18)(19)). These results demonstrate that H 2 S induces cell proliferation via exerting its dual cytoprotective and anti-apoptosis effects.…”

“…It has been reported that NF-κB can be activated by various stimuli both in normal cells (13) and in cancer cells (13)(14)(15)(16)(17)(18)(19). Herein, we found that NaHS not only activated NF-κB in PLC/ PRF/5 hepatoma cells, leading to increased phosphorylation of NF-κB p65 and IκBα, but also increased NF-κB nuclear translocation.…”

“…The activated NF-κB (p65) binds to κB sequences and alters the expression of various target genes (13). The above physiologic process also occurred in different tumor tissues or in cancer cells (14)(15)(16)(17)(18), such as breast cells, and especially in liver cancer cells (19), indicating that NF-κB is involved in oncogenesis process of liver cancer. Hydrogen sulfide (H 2 S), is an unusual virulent gas, and has been qualified as the third gasotransmitter following nitric oxide (NO) and carbon monoxide (CO) (20)(21)(22).…”

Potential biomarkers of HCC based on gene expression and DNA methylation profiles

“…is decreased in liver cancer tissue compared with control tissue, and that negative NFKBIA expression predicted poor prognosis in patients with primary HCC (48). A nested case-control study in Shanghai (China) suggested that genetic variants of NFKB1 influenced liver cancer-susceptibility in the Chinese population (49). SOCS2 has been reported to inhibit tumor metastasis (50).…”

Distribution of allelic and genotypic frequencies of IL1A, IL4, NFKB1 and PAR1 variants in Native American, African, European and Brazilian populations

“…Recently, many studies have tested the association between different forms of cancer and functional variants of genes responsible for the inflammatory process [ 5 – 8 ], such as interleukin 1A ( IL1A ), interleukin 4 ( IL4 ), nuclear factor kappa B1 ( NFKB1 ) and protease-activated receptor 1 ( PAR1 ) [ 9 – 12 ].…”