Chen Xingdong's team found new clues to the association between alcohol consumption and hepatocellular carcinoma

On October 28, 2022, the internationally renowned journal BMC Medicine published online a research paper by Chen Xingdong, a young researcher from the Institute of Human Phenomics/School of Life Sciences, Fudan University, and the team of Professor Zhang Tiejun from the School of Public Health of Fudan University “Alcohol consumption and hepatocellular carcinoma: novel insights from a prospective cohort study and nonlinear Mendelian randomization analysis”
。 The study conducted a systematic study on the classic epidemiological problem of drinking and liver cancer, which provided new clues
to this problem.

A large number of epidemiological studies have shown that alcohol consumption is one of the clear risk factors for
liver cancer.
Excessive alcohol consumption can increase the risk of liver cancer by 2-10 times, but the association between moderate drinking and the risk of liver cancer has been controversial
.
Previous studies have found that moderate alcohol intake can significantly reduce the risk of liver cancer, but some studies have believed that there is no safety threshold for drinking, that is, there is a "dose-response relationship" between drinking and liver cancer, and the risk of liver cancer continues to rise
with the increase of alcohol consumption.
To address this problem, the researchers comprehensively evaluated the relationship
between alcohol intake and hepatocellular carcinoma (HCC) using additive Cox regression models and nonlinear Mendelian randomization (NLMR) methods based on a large population cohort after excluding subjects who could not calculate precise alcohol intake and baseline patients with various chronic diseases.
The results of the study found a "J" shaped relationship between daily pure alcohol intake levels and HCC risk at the population level (Figure 1A), indicating that moderate alcohol consumption reduces the risk
of liver cancer compared with those who do not drink at all.
However, at the genetic level, NLMR analysis found no nonlinear relationship between alcohol consumption and HCC (nonlinear p-value: 0.
386; Figure 1B), suggesting that alcohol itself may not have a positive effect
on liver health.

Figure 1.
Association between alcohol intake and risk of hepatocellular carcinoma

The researchers further found that the "J" pattern of association between alcohol consumption and liver cancer was detected only in participants who primarily drank wine (Figure 2A), but not in subjects who primarily drank beer (Figure 2B), spirits, or fortified wine (Figure 2C
).
The results suggest that the "protective effect" of drinking alcohol may be caused by biologically active substances in wine
.

Figure 2.
Association of different alcohol types intake with hepatocellular carcinoma

The researchers also found that moderate wine consumption significantly reduced blood levels of alanine aminotransferase and aspartate aminotransferase (Figure 3).

Figure 3.
Association of alcohol consumption with liver enzymes

In addition, the study found that the "J" association was found only in women, adults aged < 60 years, normal alanine aminotransferase levels, and low-risk people with PNPLA3 rs738409 and TM6SF2 rss58542926 wild genotypes, while in the contrasting high-risk groups, the increase in alcohol consumption was dose-responsive with HCC risk regardless of the type of alcohol consumed
。 Compared with people at high risk of liver cancer, the proportion of individuals who mainly drink wine is higher in the low-risk group (Figure 4).

Figure 4.
The proportion of different subgroups who mainly drink wine

It is worth noting that in people at low risk of liver cancer, when the main wine drinking subjects were excluded, drinking and liver cancer showed a significant linear association, that is, there was no longer a safe threshold
for drinking.
The results further suggest that the "protective effect" of drinking alcohol may be caused by
wine.

The results of this study suggest that low- to moderate alcohol consumption may be inversely associated with the risk of HCC in people at low risk of liver cancer, which may be largely related to
wine consumption.
For people at high risk of HCC, such as men and the elderly, as well as those with abnormal ALT levels and those with genetic risk variants, there is no safety threshold for any type of alcohol, suggesting that such people should abstain completely from alcohol to reduce H CC risk
.
In general, this study not only provides new evidence and clues for the "ancient" topic of alcohol consumption and liver cancer, but also has important guiding significance
for the health management of high-risk groups of HCC.

Postdoctoral fellow Liu Zhenqiu of the Institute of Human Phenome and Associate Professor Song Ci of the School of Public Health, Nanjing Medical University are the co-first authors
of this paper.
Chen Xingdong, a young researcher, and Professor Zhang Tiejun, a professor from the School of Public Health of Fudan University, are the co-corresponding authors
of this paper.
The study was also guided by Professor Jin Li and supported
by the National Geriatrics Center of Huashan Hospital.
The research was supported
by the Boxin Program, the China Postdoctoral Science Foundation, the National Natural Science Foundation of China, the National Key Research and Development Program of China, and the Natural Science Foundation of Jiangsu Province.

Links to papers: https://bmcmedicine.
biomedcentral.
com/articles/10.
1186/s12916-022-02622-8