Alcohol and liver cancer – is there a safe limit?

We know that one of the causes of liver cancer is heavy alcohol consumption. A recent report from the World Cancer Research Fund has put a number of the amount of drinks a day at which risk increases – 3 or more alcohol drinks a day can cause liver cancer according to the report. This is the type of finding that is generally widely reported, and judging from comments in the media leads to a mixture of reactions – from broad interest to outright scepticism. It is therefore a great topic for EPICentre to delve into.

First of all it is worth noting what the authors of the report have done. They have basically reviewed all the epidemiology literature on the causes of liver cancer, including alcohol, but also other factors such as diet, contamination with aflatoxin (common in some parts of Asia and Africa), obesity and coffee – more on these later. They have done this by searching the scientific literature in a clear and transparent way, and have ended up with results from 105 scientific studies, 103 from cohort studies and 2 from randomized trials. Many types of studies were not included as they were thought to be of limited quality, for example case-control studies where individuals who already have liver cancer are asked about their exposure history and compared to controls.

The research team next tried to get summary results from the papers on the risks associated with various lifestyle habits (e.g. drinking alcohol or coffee) or conditions (body weight) and the subsequent risk of liver cancer. They have then combined these results in a ‘meta-analysis’ and produced a report that includes 56 tables and 60 figures. This work involves a lot of time and effort, and is meticulously done, and the authors should be congratulated for it. The hard bit however is interpreting the figures, and also the limits of this type of analysis.

Based on results from 14 studies, a statistically significant trend was seen for increasing alcohol consumption and subsequent liver cancer. A sub-analysis within 8 studies showed that this trend was not seen at lower categories of alcohol consumption but only kicked in at 45 grams per day or more, hence the study conclusion (the authors estimate that three drinks is about 40 grams of alcohol). The authors did however report some other results that show how difficult a simple interpretation is. First of all, there was evidence of significant publication bias, with an absence of small studies that show no effect (this is Figure 39 of their report). Maybe the studies exist but were just not published. Secondly, there were differences between the study results (i.e. study heterogeneity). Not all studies were giving the same answer, and it is therefore difficult to put them all together to come up with a simple result. Women also seemed to have higher risks than men. Thirdly, the results from the individual studies showed some interesting trends (this is in Figure 40) with a few studies showing a higher risk among non-drinkers as opposed to light drinkers. This could even have been expected. We know that alcohol causes liver cancer primarily by inducing liver cirrhosis. It could be expected that individuals who develop cirrhosis will quit drinking, and their history of previous heavy alcohol consumption may not be picked up by the studies. In a similar vein, levels of alcohol consumption are notoriously hard to measure by a questionnaire, with many people not giving an accurate answer.

All of the above means that it is extremely difficult to interpret the results from a large meta-analysis with the precision we would like. It probably has little effect on the overall conclusions however. We know that heavy alcohol consumption causes liver cancer (primarily by causing cirrhosis) as well as many other conditions, including several cancers. There probably is no safe level of alcohol consumption for cancer, and if people do decide to drink, moderation is key. Further clear guidelines on this have been published recently in the European Code against Cancer.

This does not detract from the value of the report either. While the results on alcohol stole the headlines, we at EPICentre were more interested in the increasing evidence of obesity increasing liver cancer risk and also coffee consumption reducing the risk of liver cancer. Overweight and obesity have not been considered as accepted risk factors for liver cancer up to now. Similarly, a protective effect with coffee consumption is in line with other reports of beneficial effects for a variety of health outcomes. When it comes to lifestyle and cancer, it’s not all bad news.

Paul Brennan

Paul Brennan

Paul Brennan is head of the Genetics Section at the International Agency for Research on Cancer, and also one of the EPIC principal investigators. Most of his work focuses on identifying new biomarkers and genes that are involved in some common cancers and how this knowledge can inform cancer prevention, either through identification of new risk factors or early detection.

Research Interests: Cancer aetiology and prevention.
Paul Brennan

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