Objective: We employed a large-scale pooled analysis to investigate the association of liver cancer-related mortality with being overweight/obese and total cholesterol (TC) levels, since limited and inconsistent data on these associations exist in Japan. Methods: A total of 59,332 participants (23,853 men and 35,479 women) from 12 cohorts without a history of cancer who were followed for a median of 14.3 years were analyzed. A sex-specific stratified Cox proportional hazards model adjusted for age and other potential confounders was used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for liver cancer-related mortality. Results: A total of 447 participants (266 men and 181 women) died of liver cancer within the follow-up period. Individuals classified as having a high BMI (≥25.0 kg/m2) and low TC levels (< 160 mg/dL) had a significantly increased risk for liver cancer-related mortality (HR 7.05, 95% CI 4.41-11.26 in men; HR 8.07, 95% CI 4.76-13.67 in women) when compared with those in the intermediate BMI (18.5-24.9 kg/m2) and TC (160-219 mg/dL) categories. These associations remained after limiting the follow-up duration to > 5 years. Conclusion: Being overweight/obese, combined with low TC levels, was strongly associated with liver cancer-related mortality in the EPOCH-JAPAN.
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