Dietary trace element intake and liver cancer risk: Results from two population-based cohorts in China

Dietary factors have been hypothesized to affect the risk of liver cancer via various mechanisms, but the influence has been not well studied and the evidence is conflicting. We investigated associations of dietary trace element intake, assessed through a validated food frequency questionnaire, with risk of liver cancer in two prospective cohort studies of 132,765 women (1997-2013) and men (2002-2013) in Shanghai, China. The associations were first evaluated in cohort studies and further assessed in a case-control study nested within these cohorts adjusting for hepatitis B virus infection. For cohort analyses, Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After a median follow-up time of 15.2 years for the Shanghai Women's Health Study and 9.3 years for the Shanghai Men's Health Study, 192 women and 344 men developed liver cancer. Dietary intake of manganese was inversely associated with liver cancer risk (highest vs. lowest quintile, HR = 0.51, 95% CI: 0.35-0.73; p_trend  = 0.001). Further adjustment for hepatitis B virus infection in the nested case-control study yielded a similar result (highest vs. lowest quintile, OR = 0.38, 95% CI: 0.21-0.69; p_trend  < 0.001). No significant association was found between dietary intake of selenium, iron, zinc, copper and liver cancer risk. The results suggest that higher intake of manganese may be associated with a lower risk of liver cancer in China.