Wednesday, 21 August 2019

Does alcohol really cause breast cancer?

The anti-alcohol lobby got very excited in April when a Mendelian Randomisation (MR) study suggested that there are no overall health benefits from moderate drinking. Put very simply, MR takes account of genetic differences to see if an epidemiological association has been confounded by genes or other factors.

The authors of the study chose to look at people living in a specific area of China where two genes associated with teetotalism are very prevalent. They didn't explain how these genetic differences explain the J-Curve and - more importantly - they didn't explain what relevance their findings had to countries like the UK where these genes are rare. As I said at the time...

In short, the study looks at a Chinese population and argues that the J-Curve showing lower levels of stroke risk for moderate drinkers is an artifact of genetic differences. Two genotypes - ALDH2-rs671 and ADH1B-rs1229984 - are identified as suspects. The problem is that the former 'is mainly absent among Europeans but is prevalent in populations in East Asia' and the latter 'is found in 19 to 91% of East-Asians and 10 to 70% of West-Asians, but at rates ranging from zero to 10% in other populations'. Since most of the evidence for the J-Curve comes from western countries, it is not at all obvious that this explanation would hold up outside of Asia.

Nevertheless, it was good enough for The Lancet which published an extraordinary editorial pronouncing the death of the J-Curve, declaring that there is no safe level of drinking, and calling for a Framework Convention on Alcohol Control. Hello confirmation bias, my old friend.

The 'no safe level' claim is largely based on epidemiological studies of drinking and breast cancer, which purportedly show an increase in risk from very low levels of alcohol consumption. The evidence for this, in fact, very weak and a new MR study - currently in pre-print and based on a large sample of people in the UK - has found that the relationship between drinking and breast cancer doesn't exist at all. Moreover, it found that there is a threshold (ie. a safe level) for the handful of rare cancers that are genuinely associated with alcohol consumption.

Alcohol was observationally associated with cancers of the lower digestive system, head and neck and breast cancer. No associations were observed when we considered those keeping alcohol consumption below the recommended threshold of 14 units/week. When Mendelian randomisation was used to assess the causal effect of alcohol on cancer, we found that increasing alcohol consumption, especially above the recommended level, was causal to head and neck cancers but not breast cancer.
Our results where replicated using a two sample MR method and data from the much larger COGS genome wide analysis of breast cancer. We conclude that alcohol is causally related to head and neck cancers, especially cancer of larynx, but the observed association with breast cancer are likely due to confounding. The suggested threshold of 14 units/week appears suitable to manage the risk of cancer due to alcohol.

Strangely, the temperance lobby alcohol research community hasn't said much about this, even though it was reported in New Scientist.

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