Genetic polymorphism of NFKB 1 and NFKBIA genes and liver cancer risk : a nested case – control study in Shanghai , China

Correspondence to Professor Y-B Xiang; ybxiang@shsci.org ABSTRACT Objectives: Genetic 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. Design: The 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). Settings: This population-based study was conducted in urban Shanghai, China. Participants: A 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 measures: Genetic 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. Results: After 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. Conclusions: Our results suggest that genetic variants of NFKB1 influence liver cancer susceptibility in Chinese population, although replication in other studies is needed. INTRODUCTION Liver cancer is a common disorder worldwide which ranks the fifth and seventh most common cancer among men and women. It was estimated that more than 80% of liver cancers occur in developing countries and about 54% occur in China. Among the main risk factors for liver cancer, chronic infections of hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most important in humans, accounting for more than 70% of liver cancer cases worldwide. Liver cirrhosis, heavy alcohol consumption, exposure to aflatoxin and diabetes also account for part of liver cancer occurrence. Chronic inflammation has been widely accepted to play an important role in hepatocarcinogenesis. Most of the known risk factors of liver cancer such as HBV, HCV infection and alcohol drinking can cause persistent inflammatory reaction of the liver and promote cancer development. 6 However, the molecular and cellular mechanisms linking inflammation and liver cancer remain unclear. Recent findings have Strengths and limitations of this study