Drinking alcohol regularly increases cancer risk in Chinese populations

A new study demonstrates that reducing alcohol consumption in China could be an important cancer prevention strategy. Full story on the NDPH website.

For Western populations, there is a well-established association between regular alcohol consumption and a greater risk of various types of cancer. However, it was unknown whether these increased risks were the same for Eastern populations, which have very different drinking patterns and alcohol tolerance. Cancer rates are rising rapidly in China, and this may be partly due to more frequent alcohol consumption as citizens become more affluent. A new study led by NDPH on the large China Kadoorie Biobank has investigated this, with the findings published today in the International Journal of Cancer.

The study assessed over half a million adults recruited across ten diverse regions in China between 2004 and 2008. Each participant was questioned about their drinking habits, then followed up for a median period of 10 years. By the end of the study, almost 27,000 individuals had developed cancer (13,342 men, 13,619 women).

About a third of the men in the study drank regularly (at least once every week). Compared with those who abstained from alcohol, regular drinkers had a 26% higher risk for cancers previously associated with alcohol (ie, mouth/throat, oesophagus, colon-rectum and liver) and a 7% higher risk for all types of cancer. The risks were greater in those who drank daily or drank outside of meals.

For most of the cancers investigated, there was a clear dose-response relationship. Each 280 g/week higher alcohol intake was associated with an increased risk of 98% for oesophageal cancer; 74% for mouth/throat cancer; 52% for liver cancer and 19% for colon-rectum cancer. The study also found that each 280 g/week higher alcohol intake increased the risk of lung cancer (25%) and gallbladder cancer (60%), even though these cancers had not previously been clearly linked with alcohol.

In East Asia, many people cannot metabolise alcohol effectively due to an inherited deficiency in the enzyme aldehyde dehydrogenase 2. This causes the carcinogenic compound acetaldehyde to accumulate, which can lead to facial flushing. In this study, those who experienced flushing after drinking had stronger associations between alcohol intake and cancer risk, particularly for oesophageal and lung cancer. This suggests that the risk of developing cancer is greater for those with low alcohol tolerability.

The associations remained strong when the researchers controlled for potential confounding variables including age, region, education, income, body mass index, physical activity, and fresh fruit intake. The association between alcohol and lung cancer was similar for regular smokers and those who had never smoked regularly. Nevertheless, large-scale genetic studies are needed to determine if the associations between alcohol and cancer are likely to be causal.

Very few women in the study drank alcohol regularly, hence the study was unable to assess whether the association between alcohol and cancer risk was the same for women.

Lead author Dr Pek Kei Im said: ‘Our study has clearly shown that among Chinese men, alcohol consumption is associated with increased risks of several types of cancer, including some that were less clearly established to be alcohol-related previously. This suggests that lowering population levels of alcohol consumption is an important strategy for cancer prevention in China.’

Developing a system to simultaneously detect genetic and epigenetic information

Many diseases are associated with changes to the DNA sequence, most notably cancer. Also altered in disease is the way that the DNA is decorated with chemical modifications such as methylation (epigenetic modifications). Being able to extract genetic and epigenetic information using DNA sequencing has revolutionised biomedical research and has led to new ways to diagnose diseases. A particular interest currently is in using genetic and epigenetic characteristics of tumour DNA circulating in the blood or other bodily fluids as a strategy for detecting cancer earlier. However, despite the potential utility of combining genetic and epigenetic information to enhance disease detection, no methods currently exist that can efficiently simultaneously extract this information from the same DNA sequencing data.

Up until now, DNA methylation has predominantly been detected using methods that rely on a process called bisulphite conversion. Bisulphite is a harsh chemical that damages DNA, resulting in decreased sensitivity and a high error rate in the sequencing data. Because it is not known whether any changes in the DNA compared to a reference genome are introduced by bisulphite or real mutations, it is very challenging to simultaneously detect methylation and mutation data using these methods.

Recently, a new bisulphite-free method for detecting DNA methylation called TET-assisted pyridine borane sequencing (TAPS) has been developed by Ludwig Oxford’s Dr Chunxiao Song and Dr Benjamin Schuster-Böckler. This method is both cheaper than bisulphite sequencing and importantly produces data of higher quality, similar to that of standard DNA sequencing.

In this project, funded by an MRC Methodology Research Grant, Dr Benjamin Schuster-Böckler will collaborate with Professor Gerton Lunter (Visiting Professor, Radcliffe Department of Medicine) to develop algorithms that simultaneously detect mutations and DNA methylation from TAPS data.  Experimental data will be provided in collaboration with Ludwig Oxford’s Dr Chunxiao Song and Professor Xin Lu, and Professor Ellie Barnes (Nuffield Department of Medicine). Test data will be used to train machine-learning algorithms to optimise the accuracy of the sequencing method and to establish the best possible experimental parameters for this technique.

The resulting method will greatly increase the utility of the TAPS technique and will make it possible to routinely query a patient’s genetic background, while simultaneously measuring their epigenetic state. This will lead to a much broader understanding of the role of epigenetics in disease and would raise the possibility of using combined genetic and epigenetic information from sequencing data to aid earlier detection of cancer.

Image attribution: Darryl Leja, National Human Genome Research Institute (NHGRI) from Bethesda, MD, USA, CC BY 2.0 https://creativecommons.org/licenses/by/2.0, via Wikimedia Commons