The rate of developing esophageal squamous cell carcinoma (ESCC) nearly doubles in those who both smoke and drink compared to those who only smoke or drink, according to new research published in The American Journal of Gastroenterology. Although multiple studies have identified risk factors for the development of ESCC, notably, exposure to alcohol and tobacco, this research is the first meta-analysis to look at the interaction between alcohol and tobacco in the risk of ESCC, a class of esophageal cancer that begins in the flat cells lining the esophagus. 
 
 "Our study suggests that not only do alcohol and tobacco play an important role in the development of esophageal cancer, the combination of their use markedly increases their potency as carcinogens. As a result, we as physicians should focus efforts directed at controlling the burden of esophageal cancer on those who consume both of these substances," said lead author Anoop Prabhu, MD, Advanced Endoscopy Fellow at the Icahn School of Medicine at Mount Sinai, in New York, NY. 
 
 Dr. Prabhu, and authors Drs. Kenneth O. Obi and Joel H. Rubenstein at the University of Michigan Medical School, performed a systematic literature search in multiple electronic databases and looked at population-based case-control or cohort studies of ESCC that assessed the effects of tobaccos and/or alcohol. A synergy factor was calculated from each study to estimate the interaction on a multiplicative scale between tobacco and alcohol on the outcome of ESCC. 
 
 "Our systematic review confirmed the expected exposure-dependent relationship of both alcohol and tobacco with the risk of ESCC, as alcohol use and tobacco use were both independent risk factors for the development of ESCC," stated Dr. Prabhu. 
 
 According to the National Cancer Institute, it is estimated in 2014 there will be over 18,000 new cases of esophageal cancer in the United States, and over 15,000 deaths from the disease. ||||| "Grape or grain, but never the twain." So runs the old folk wisdom that advises against drinking wine or beer on the same night. It is far from uncommon to hear people who have woken up feeling sick, dehydrated and with a splitting headache blaming their hangovers on having unwisely mixed their drinks. 
 
 Then there are the theories about the order in which to consume different tipples. One version suggests: “Wine before beer and you’ll feel queer. Beer before wine and you’ll feel fine.” Or is it the other way round? After a couple of drinks it’s not always easy to remember. All of which begs the question of how reliable these sayings are. Is there any evidence beyond the anecdotal that drinking wine followed by beer or vice versa makes hangovers worse? 
 
 A review of previous research published in 2000 confirms that the causes of the main symptoms of hangovers are dehydration, changes in the levels of hormones such as aldosterone and cortisol, and the toxic effects of alcohol itself. In addition there’s evidence that the immune system is disrupted and that this could be the cause of the headache, the nausea and the fatigue. 
 
 
 
 The first of the two main ingredients of a drink that affect the severity of a hangover is obvious. The higher the alcohol content, and the faster you drink it, the worse the hangover. This is however just an average. The same quantity of alcohol does not always result in the same severity of hangover. Many report that they don’t get hangovers and no one quite knows why. In a study of young Danes on holiday, almost a third of those who consumed at least 12 units of alcohol (roughly equivalent to four pints of lager or four 250ml glasses of wine) avoided hangovers. 
 
 Mixing drinks needn’t necessarily increase the overall amount of alcohol consumed, but it may do with cocktails. If combining three or four measures of spirits alongside other ingredients, a throbbing head and dry throat is probably just the result of consuming more alcohol in total. 
 
 Beyond the ethanol that triggers intoxication, the other key ingredients that affect hangovers are what the beverage industry calls congeners. These are the other substances produced during fermentation, such as acetone, acetaldehyde, fusel oil and the best-known, tannins, which give darker drinks their colour and part of their flavour. Bourbon whisky, for example, contains 37 times the quantity of congeners as vodka. 
 
 To find out the effect of these substances on hangover severity, researchers in the US recruited university students who were regular drinkers, without alcohol problems. On different nights they were given either bourbon and cola, vodka and cola or a placebo which consisted of cola mixed with tonic, with a few drops of either bourbon or vodka to make it taste similar to the real stuff. They drank anything between three and six drinks, however much was enough to give them a concentration of 0.11g of alcohol per 100ml of breath. This would put them two to five times over the drink drive limit, depending which country they were in. They then spent the night in the clinic and were woken at 7am for breakfast before taking part in a battery of tests. For this they were paid a rather generous $450. The researchers found the students who drank bourbon rated their hangovers as worse, but interestingly they performed just as well on tasks such as reaction time tests. 
 
 Clear drinks such as white rum, vodka and gin tend to cause fewer and less severe hangovers because they contain relatively low levels of congeners. Perhaps those who mix their drinks are more likely to choose a dark-coloured drink containing higher levels of these substances simply by virtue of their wider drinking range, but again it isn't the mixing in itself that causes the problem. 
 
 No scientist seems to have done the perfect counter-balanced study where people are randomly assigned to drink beer followed by wine or wine followed by beer. But perhaps it’s not the grape or the grain that matters, but the effect that the strength of those drinks has on judgement. Beer is only between a third and half the strength of wine, so starting on it leads to less intoxication if followed by the stronger stuff. But if a person starts on wine or spirits, then their judgement may be impaired enough to drink more heavily later. There’s certainly evidence that people are not good at judging their own drunkenness. At low levels people overestimate the amount of alcohol in our blood, but after a few drinks they start to underestimate it. 
 
 So, the existing evidence suggests that hangovers can't be blamed on mixing drinks. It's probably down to the high congener count of the booze, or over-drinking. As for hangover cures, scientists have looked into those too, and the British Medical Journal published a review of trials of everything from borage to artichoke and glucose to prickly pears in 2005. The bad news for drinkers is that none of them work. 
 
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– Many of us may avoid downing hard alcohol, wine, and beer on the same night for fear of a raging hangover the next day. But at the BBC, a review of existing research on the topic suggests the drinks' variety itself isn't the problem. Instead, Claudia Hammond points to other possible factors. For instance, she notes, having several different types of drinks may simply mean drinking more total alcohol. (As for "beer before liquor, never been sicker"? It appears no research has been done to prove or disprove the idea that drink order makes a difference.) "The existing evidence suggests that hangovers can't be blamed on mixing drinks," Hammond writes. But the amount of alcohol may not be the only culprit: Congeners, the non-ethanol products of the fermentation process, also contribute to a hangover. Tannins, for instance, are responsible for the color in darker types of alcohol. There are 37 times more congeners in bourbon than in vodka, and one study found that bourbon drinkers reported worse hangovers than those who drank vodka. So, Hammond writes, people having various types of drinks in a single night may end up indulging in drinks with more tannins. So go ahead and mix types of alcohol if you so desire, but you may want to avoid mixing alcohol with cigarettes: A study last month found that people who smoke and drink are at a higher risk of developing esophageal cancer, Science Daily reported. (If you do find yourself with a hangover, you may want to reach for a Sprite.)