Low-Carbohydrate Diet Score and Risk of Hepatocellular Carcinoma: Findings from a Prospective Cohort Study

Limited data are reported on the association between low-carbohydrate diet (LCD) score, a comprehensive measure of dietary pattern according to sources of carbohydrate, fat, and protein, and risk of hepatocellular carcinoma (HCC). We evaluated this score with HCC risk in the Singapore Chinese Health Study, a prospective cohort of 63,275 middle-aged and elderly Chinese living in Singapore and recruited during 1993–1998 period. LCD scores were derived from the semi-quantitative food frequency questionnaire at baseline. A nested case–control study involved 197 HCC cases and 465 controls was also constructed among 28,346 participants who provided blood samples. Cox proportional hazard regression method was used to calculate HRs and 95% confidence intervals (CI) for HCC with different levels of LCD scores. Conditional logistic regression was performed for the case–control study analysis. After 17.6 years of followup with 819,573 person-years, 561 participants developed primary HCC. Although there was a null association between total LCD score and HCC risk (HR_{per-SD increment} = 1.07; 95% CI, 0.98–1.16; P_trend = 0.06), there was a positive association between animal-based LCD and the risk of HCC (HR_{per-SD increment} = 1.11; 95% CI, 1.02–1.21; P_trend = 0.01). Furthermore, this association was present in both HBsAg-negative and HBsAg-positive individuals in the case–control study. In stratified analysis for the entire cohort, this positive association was only present in those who consumed alcoholic beverages monthly or less frequent but not in weekly or daily drinker (P_interaction = 0.79). In summary, a diet with lower carbohydrate, higher animal fat and protein was significantly associated with higher risk of HCC among Chinese Singaporeans.