Tuesday, May 27, 2008

DNA again: Low cancer risk for big drinkers

Another entry in the old alternating good for you, bad for you, good for you farce

The genes that regulate how quickly people get drunk also influence their risks of developing cancer of the mouth, larynx or gullet, a new study has found. People with a fast-acting variant of the gene for alcohol dehydrogenase - the enzyme that breaks down alcohol - were at much lower risk of these cancers, according to scientists collaborating in the international study. The reason, they conclude in Nature Genetics, is that these hyper-active enzymes break down alcohol, which is a toxin, more quickly.

This means that the mouth and throat are exposed to the damaging effects of alcohol for a shorter period, with a lower chance that cancer will be initiated. The study was led by Paul Brennan of the University of Aberdeen and incorporated data from almost 4,000 cases of cancer and more than 5,000 healthy people from Europe and Latin America.

There are known to be many variants of the alcohol dehydrogenase gene, which determine in part how susceptible people are to drinking. Its true purpose is to convert the alcohol created by bacteria in the gut into aldehydes, and then, via another enzyme, into harmless substances. Since the invention of brewing thousands of years ago, however, the alcohol and aldehyde enzymes have found themselves a much bigger task - detoxifying alcohol drunk for pleasure. Some people who lack the enzyme cannot drink even small amounts without becoming drunk.

The new study looked at the frequency of six variants of the alcohol dehydrogenase gene in the cancer cases and compared it with the frequency of the same six variants in people who had not developed cancer. It identified two variants that are particularly powerfully protective, called rs1229984 and rs1573496. People with the rs1229984 gene are known to break down alcohol 100 times faster than those without it. The results showed that both these genes protect against cancer, and are particularly powerful in combination. Those who carry both genes were 55 per cent less likely to develop any of the cancers studied.

Dr Tatiana Macfarlane, senior lecturer at the University of Aberdeen's department of general practice and primary care, and one of the authors, said: "The study showed that your risk of getting oral cancers is linked to genetics as well as lifestyle. "We found that, in particular, the risk depends on how fast your body metabolises alcohol. "The results suggest that the faster you metabolise it, the lower your risk. "These results provided the strongest evidence yet that alcohol consumption is strongly linked to oral cancers. "The risk is particularly high if you also smoke or rarely eat fruit and vegetables."

Professor Gary Macfarlane, chair in epidemiology at the University, said: "At a time when we are concerned about the levels of alcohol consumption in the United Kingdom, these results demonstrate the public health importance of measures to reduce consumption and prevent deaths at young ages from diseases, including oral cancers."

In healthy people, neither of these gene variants seems to be linked to the amount of alcohol consumed. If possessing these protective genes encouraged people to drink more - because they metabolised alcohol more quickly - then any benefit would be eroded. But in fact there is no link between the genes and drinking habits. Equally, the genes do not have any effect on cancer risk among non-drinkers.

The only possible conclusion, say the authors, is that the protective effect comes from the greater ability of the carriers of these genes to break down alcohol before it can do so much harm


Rogue DNA can lead to nutritional deficincies

That some people can have nutritional deficiences because of their genes clearly detonates a lot of simplistic thinking. All men are NOT equal, once again

WHEN Michael Fenech sits down to dinner, he looks at the food on his plate rather differently to the rest of us. For Fenech, a principal researcher with the CSIRO's Human Nutrition centre in Adelaide, tasty morsels of meat and vegetables are more than just fuel to keep his body running. They also contain nutrients that have the potential to protect his DNA from serious damage, and affect his chances of falling ill.

Fenech has spent the past 20 years studying the nutrients we need to keep our genes healthy, and how our genetic make-up influences the way we respond to food. That work has put him at the forefront of a new scientific discipline known as "nutrigenomics", which brings to bear a detailed understanding of how humans differ from one another in genetic terms and applies it to the traditional science of nutrition.

It's also a field that's poised to take on growing importance given the recent political emphasis on "preventive" health care, as highlighted in this week's federal budget. Advocates say nutrigenomics could allow us to tailor our diets to our individual genetic characteristics -- potentially helping us lose weight more effectively, avoid cancer, say goodbye to binge drinking and live to a ripe old age.

Folate -- a vitamin found in leafy vegetables, fortified grain products and other foods -- is a good example of how nutrients can affect our genes, Fenech says. "When one has inadequate intake of folate, the DNA in the cells can be damaged, or fragmented, or the expression of the genes can be altered," he says. This can have a dramatic effect on our chromosomes, causing as much damage as carcinogenic doses of radiation. Similar damage may result from deficiencies in other nutrients such as calcium, magnesium, retinol, nicotinic acid, vitamin E and vitamin B12, adds Fenech. And as our cells grow and divide the damage can accumulate, a problem associated with infertility, developmental defects in the foetus, cancer, Alzheimer's disease and other conditions.

But avoiding these unhealthy outcomes is not a simple matter of everyone boosting their nutrient intake a certain amount, Fenech says. Each of us carries within our cells different forms of genes that affect how our bodies absorb and use the nutrients we need, such as folate and vitamin B12. "At this point in time, we're assuming that the nutritional requirements are the same for everyone and that everyone absorbs the nutrients in the same way -- well, that's not the case."

Fenech's work is giving us an important insight into the detailed mechanics of how good dietary choices keep us healthy, says nutritionist Rosemary Stanton. "Michael Fenech is a genuinely good researcher," she says. "The sort of work he does may offer some really important solutions for some people."

In 2005, Fenech and his CSIRO colleagues developed a test that specifically measures the amount of damage present in human DNA, dubbed the "cytokenesis-block micronucleus cytome (CBMN Cyt) assay." Since last year, the test has been used by an Adelaide health clinic called Reach 100. For a fee of roughly $600 per test, the clinic offers patients a chance to have their level of DNA damage measured by CSIRO scientists, and then provides tailored suggestions on how to improve it through dietary supplements and lifestyle changes.

Beyond preventing DNA damage, nutrigenomics suggests there might be other ways to personalise our diet according to our genetic make-up. One particular gene, called apolipoprotein E (APOE), for example, can have a dramatic impact on your risk of heart disease and diabetes, depending on which variant you carry. About one in five people carries a specific variant of the gene that raises cholesterol, increases diabetes and Alzheimer's risk and reverses the protective effects of moderate alcohol drinking.

Individuals with that genotype should be careful about their diet and exercise, and in particular should give up or avoid smoking and alcohol, Lynn Ferguson from Nutrigenomics New Zealand wrote in the journal Molecular Diagnosis & Therapy in 2006. "However, very few of the population are aware of their APOE genotype at present."

Fenech adds that genes can also partly determine how well you do on particular diets. "We know that there is variation in people's response to weight-loss diets and the genetic basis of that response is being unravelled," he says. "That is actually being worked out now."


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