Professor Zhang Tiejun of our institute and researcher Xingdong Chen of the Institute of Human Phenomics teamed up to discover new clues about the association between alcohol consumption and hepatocellular carcinoma

(Contributed by: Fan Hong)

Recently, the internationally renowned journal BMC Medicine published online the research paper "Alcohol consumption and hepatocellular carcinoma: novel insights from a prospective cohort study and" by Professor Zhang Tiejun of the School of Public Health of Fudan University and the research team of Chen Xingdong of the Institute of Human Phenomics/School of Life Sciences 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 solve this problem, the researchers comprehensively evaluated the relationship
between alcohol intake and hepatocellular carcinoma (HCC) using additive Cox regression model and nonlinear Mendelian randomization (NLMR) methods based on a large population cohort.
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

In addition, the "J" association was found only in female, 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.
The proportion of individuals who primarily drink wine is higher in the low-risk group compared to those at high risk of liver cancer (Figure 2).

Figure 2.
The proportion of different subgroups who mainly drink 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 from alcohol altogether to reduce HCC 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.

Liu Zhenqiu, a postdoctoral fellow at the Institute of Human Phenotyping of Fudan University, and Associate Professor Song Ci of the School of Public Health, Nanjing Medical University, are the co-first authors of this paper, and Xingdong Chen, researcher of the Institute of Human Phenotyping of Fudan University, and Professor Zhang Tiejun of the School of Public Health of Fudan University are the co-corresponding authors of this paper, and the study was also guided
by Professor Jin Li 。 The research was supported
by the National Innovation Talents Postdoctoral Grant Program (BX2021077), the China Postdoctoral Science Foundation (2021M700841), the National Natural Science Foundation of China (82073637, 82122060), the National Key Research and Development Program of China (2019YFC1315804, 2019FY101103), and the Natural Science Foundation of Jiangsu Province (BK20190652).

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