Abstract

Background: Liver cancer is the second most fatal cancer in the world. China is disproportionally affected, accounting for approximately 50% of liver cancer cases and deaths worldwide. Major risk factors for liver cancer include chronic hepatitis B and C viral infections, aflatoxin B1 exposure, alcoholic consumption, and tobacco smoking. Objective and Methods: We aimed to update the fraction of liver cancer cases attributable to these known risk factors, as well as estimate attributable risk of obesity for liver cancer at country, regional, and global levels. At the individual level, a population-based case-control study was conducted in a high risk area of China, Jiangsu Province, to evaluate novel associations between dietary intakes of flavonoids as well as glycemic index and load with liver cancer, and to assess original relationships of single nucleotide polymorphisms of NF-κB, the stem cell pathway, and GWAS SNPs with liver cancer. The association between SNPs and liver cancer was additionally stratified by flavonoid intake. Results: In the global analyses, we found that most liver cancer cases could be attributed to viral hepatitis, particularly in low income regions. Alcohol consumption was the strongest lifestyle risk factor, and patterns varied geographically. In the case-control study, we observed marginal and inverse associations between total flavonoid consumption and liver cancer, driven in largely by the protective association between tea consumption and liver cancer. Carbohydrate intake was associated with increased odds of liver cancer. No obvious association between SNPs of the NF-κB pathway and liver cancer was observed, however, genetic risk scores of SNPs of the stem cell pathway and those identified in GWAS studies were associated with liver cancer. Furthermore, we found that dietary flavonoid intake modified the associations between liver cancer and selected SNPs. Conclusion: This study provides policy-makers updated and regionally specific estimates of the burden of cancer. The results from the case-control study support a marginally protective effect of dietary flavonoid consumption, and a marginal increase in susceptibility associated with increased glycemic load and liver cancer in a Chinese population. Furthermore, there was evidence that dietary intake may modify the associations between some SNPs and liver cancer.