Alcohol consumption and hepatocellular carcinoma: novel insights from a prospective cohort study and nonlinear Mendelian randomization analysis

Abstract

Background Heavy drinking was well associated with an increased risk of hepatocellular carcinoma (HCC), whereas the effect of low-to-moderate drinking on HCC remains under debate. Methods Participants from the UK Biobank with detailed information on alcohol use and free of common diseases were included. Daily pure alcohol intake (g/day) was calculated, and the predominant alcoholic beverage type was assigned for each participant. Additive Cox regression model and nonlinear Mendelian randomization (NLMR) analyses were performed to evaluate the association of alcohol intake with HCC. Results Of 329,164 participants (52.3% females, mean [SD] age = 56.7 [8.0] years), 201 incident HCC cases were recorded during the median follow-up of 12.6 years. The best-fitted Cox regression model suggested a J-shaped relationship between daily alcohol intake level and HCC risk. However, NLMR analysis did not detect a nonlinear correlation between alcohol use and HCC (nonlinearity P-value: 0.386). The J-shaped correlation pattern was detected only in subjects who mainly drank wine but not in those who mainly drank beer, spirits, or fortified wine. Moderate wine drinking showed a significant alanine transaminase (ALT)- and aspartate aminotransferase-lowering effect compared to that of the nondrinkers. In low-risk populations of HCC including women, people aged < 60 years, subjects with normal ALT levels, and those carrying non-risk genotypes of PNPLA3 rs738409 and TM6SF2 rs58542926, we observed a J-shaped correlation between alcohol use and HCC; however, a positive dose–response correlation was found in their respective counterparts, even in those predominantly drinking wine. Conclusions Low-to-moderate drinking may be inversely associated with the risk of HCC in low-risk populations, which may be largely driven by wine drinking. However, those in high-risk populations of HCC, such as men and older people, and those with abnormal ALT levels and carry genetic risk variants, should abstain from drinking alcohol. Given the small HCC case number, further validations with larger case numbers are warranted in future works.

Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study

“… 19 For alcohol consumption, the current frequency and volume of alcohol consumption were recorded, and individuals were categorised into never drinking (never drank or drank occasionally), low to excess drinking (daily alcohol consumption of 1-60 g), and heavy drinking (daily alcohol consumption >60 g). 20 The category of never drinking was deemed a healthy lifestyle factor. 21 The remaining three lifestyle factors were deemed healthy based on the top 40% of the population distribution, according to previous studies.…”

“…Never or former smoking was deemed a healthy lifestyle factor 19. For alcohol consumption, the current frequency and volume of alcohol consumption were recorded, and individuals were categorised into never drinking (never drank or drank occasionally), low to excess drinking (daily alcohol consumption of 1-60 g), and heavy drinking (daily alcohol consumption >60 g) 20. The category of never drinking was deemed a healthy lifestyle factor 21.…”

Global prevalence, incidence, and outcomes of alcohol related liver diseases: a systematic review and meta-analysis

“…Some studies proposed that moderate drinking was beneficial to health [ 414 – 416 ], but the defined alcohol intake and types of alcohol have not reached a consensus. American Association for the Study of Liver Diseases has set a safe threshold of alcohol consumption for men (no more than 2standard drinks per 24 h) and women (no more than 1standard drinks per 24 h) [ 417 ].…”

Alcohol and its associated liver carcinogenesis

“…11 There may also be an inverse relationship between low-level alcohol consumption and HCC risk as demonstrated in a nonlinear Mendelian randomization analysis on UK biobank data. 12 Furthermore, an umbrella meta-analysis demonstrated a 27% reduction in HCC risk associated with low alcohol consumption (relative risk 0.73, 95% CI 0.54-0.98). 13 Cessation of alcohol consumption also reduces the risk of HCC development by 6-7% annually and should therefore be encouraged in ALD patients.…”