Total cholesterol, alanine aminotransferase and the risk of primary liver cancer: A population-based prospective study in China

Abstract Background: Previous studies have shown that serum total cholesterol(TC) and serum alanine aminotransferase(ALT) were associated with liver cancer risk, respectively. However, the common contribution of TC and normal-high ALT to primary liver cancer(PLC) has not been reported to date. We aim to assess the separate and joint effect of low TC level and normal-high ALT level on the risk of PLC, a large prospective cohort was conducted in our study. Method: The participants were divided into 4 groups via mismarch method according to TC[low level(-)/ non-low level(+)] and ALT[normal level(-)/ normal-high level(+)] status, and using the lower quartile(P25) value(4.24 mmol/L) of TC and the upper quartile(P75) value(22 U/L) of ALT as a cut point, respectively. Incident PLC was confirmed by review of medical records. Cox proportional hazards regression models and interactive additive models were used to evaluate whether the joint effect of low TC level and normal-high ALT level is associated with the risk of PLC. Results: During 1,248,895 person-years of follow-up, 298 participants were diagnosed with PLC among 114,972 subjects. TC＜4.24 mmol/L for the “TC(-)” group; TC≥4.24 mmol/L for the “TC(+)” group; ALT＜22U/L for the “ALT(-)” group; ALT≥22U/L for the “ALT(+)”. Compared with the “TC(+)” group and “ALT(-)” group, respectively, the adjusted hazard ratio(HR) and 95% confidence interval(95%CI) of “TC(-)” group for PLC risk was 1.71 (1.34-2.19) and of “ALT(+)” group for PLC risk was 1.52 (1.18-1.95). In combinatorial analysis, compared with the group of “TC(+) with ALT(-)”, the significant increased risk of PLC were observed in “TC(+) with ALT(+) group”(HR=1.45; 95%CI: 1.07-1.97), “TC(-) with ALT(-)” group(HR=1.64; 95%CI: 1.21-2.22) and “TC(-) with ALT(+)” group(HR=2.70; 95%CI: 1.84-3.96), respectively. The interaction term between “TC(-)” and “ALT (+)” on the risk of PLC was not significant(Pinteraction=0.26). Conclusions: Both low TC level and normal-high ALT level were strong predictors of PLC. Individuals with low TC level and normal-high ALT level, would extremely increase the risk of PLC.Trial registration: ChiCTR-TNRC-11001489. Registered August 24, 2011 (retrospectively registered)