Evidence has suggested a potential link exists between trimethylamine-N-oxide (TMAO), a choline-derived metabolite produced by gut microbiota, and some cancers, but little is known for primary liver cancer (PLC). A case-control study was designed including 671 newly diagnosed PLC patients and 671 control subjects frequency-matched by age (±5 years) and sex, in Guangdong province, China. High-performance liquid chromatography with online electrospray ionization tandem mass spectrometry (HPLC-MS/MS) was used to measure serum TMAO and choline. The associations between these biomarkers and PLC risk were evaluated using logistic regression models. Serum TMAO concentrations were greater in the PLC group than the control group (P = 0.002). Logistic regression analysis showed that the sex- and age-adjusted odds ratio (OR) and (95% confidence interval [CI]) was 3.43 (2.42–4.86) when comparing the top and bottom quartiles (Q4 vs Q1). After further adjusting for more selected confounders, the OR (95% CI) remained significant but was attenuated to 2.85 (1.59–5.11) (Q4 vs Q1). The multivariable-adjusted ORs (95% CIs) across quartiles of choline were 0.35–0.15 (P-trend < 0.001). Higher serum levels of TMAO were associated with increased PLC risk. The association was stronger in those with lower serum levels of choline. Additional large prospective studies are required to confirm these findings. This study was registered at clinicaltrials.gov as NCT 03297255 .

Adherence to healthy dietary guidelines has been related to a lower risk of several cancers, but its role in primary liver cancer (PLC) has not been fully investigated, especially among Eastern populations. This study enrolled 720 PLC patients and 720 healthy controls who were frequency-matched by age and sex between September 2013 and October 2017 in South China. Dietary quality was assessed by the Chinese Healthy Eating Index (CHEI) and the Healthy Eating Index 2015 (HEI-2015), which manifests as scores of adhering to the 2016 Dietary Guidelines for Chinese and adhering to the 2015–2020 Dietary Guidelines for Americans, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models, adjusting for potential confounders. Higher scores in both the CHEI and HEI-2015 were associated with a lower risk of PLC (per 5-points increment of the total scores: OR: 0.43, 95% CI: 0.38–0.50 for CHEI; OR: 0.47, 95% CI: 0.40–0.55 for HEI-2015). The protective associations persisted significantly in the stratified analyses by sex, smoker status, alcohol consumption, HBV infection, and histological types of PLC, without statistical evidence for heterogeneity (p-interaction > 0.05). Closer adherence to the most recent dietary guidelines for Chinese or Americans may protect against PLC.