Tuesday, April 10, 2007

High African prostate cancer risk tied to DNA

A team led by Harvard researchers has found dramatic genetic links to prostate cancer that appear to underlie many of the cases and help explain the higher occurrence of the disease among African-American men. The scientists said yesterday that they have identified a set of changes in human DNA that are common in the American population and that, together, can increase the risk of the disease by more than five times. These changes may be responsible for up to two-thirds of African-American cases and one-third of the cases among Caucasian-Americans, according to a report in the journal Nature Genetics. The discovery may eventually allow doctors to improve screening, a strategy that has had an impact on the disease, by identifying high-risk people to be tested at an earlier age. And it could someday lead to better treatments for the second-leading cancer killer of men.

The finding also poses a compelling mystery. All the dangerous genetic changes identified lie in stretches of DNA that contain no genes and have no known biological function. This, researchers said, suggests that scientists are now on the trail of a new mechanism behind cancer, and it raises the possibility that this mechanism is behind some other forms of cancer. "It is a smoking gun to something new," said Dr. Tom Hudson, who was not involved in the research and is president and scientific director of the Ontario Institute for Cancer Research in Toronto. "It is very exciting."

The field of prostate cancer genetics is moving rapidly. Last year, deCODE Genetics, a company in Iceland, identified the first genetic variant, a portion of DNA that is different from the rest of the population's, which is associated with a 60 percent increase in risk of prostate cancer. The new work, led by David Reich of Harvard Medical School, identified five variants. These six variants , as well as another one already found, are more common in Americans with African ancestors than those with European ancestors, Reich said. The study suggests that genetics are a powerful reason for African-Americans' greater susceptibility to prostate cancer. African-Americans are 56 percent more likely to get the disease than Caucasian men, and 2 1/2 times more likely to die of it, according to the Prostate Cancer Foundation in Santa Monica, Calif.

Reich cautioned, however, that scientists could not tell from the research how much the genetic variants contribute to the disparity in the incidence or death rate of the disease. Other factors, including genetic changes that have not been identified and the environment, may play a role in the disease's higher incidence among African-Americans.

The new variants were identified by studying the DNA of 7,500 people, some of whom had prostate cancer. The research team focused on a particular region on chromosome 8, which previous research, including the deCODE work, has implicated in the disease. They looked for DNA variants that victims of prostate cancer tended to have, but healthy people did not


Defeating malaria with both high- and low-tech

O death, where is thy sting? Far too often it comes at the end of a mosquito's proboscis. The worst mosquito-borne disease, malaria, infects about 400 million people worldwide each year (90 percent in sub-Saharan Africa) and kills about 1.3 million of them. So it's great that scientists at the Malaria Research Institute at Johns Hopkins University in Maryland have genetically built a better mosquito, which is to say that it still bites and leaves an itchy welt but cannot spread malaria. The idea is that large numbers of engineered mosquitoes would be released in malaria-ridden areas so they could interbreed with wild ones. Over time more and more of the mosquito population would carry the new trait.

This is not a new concept. Various types of harmful male insects are irradiated to make them sterile, and then released to interbreed with fertile bugs and thereby reduce the overall population. The problem with sterilization, though, is that it often weakens the insect and gives fertile wild competitors the advantage in breeding.

But these biotech mosquitoes actually have a breeding advantage. Mosquitoes infected with the malaria parasite, Plasmodium, don't die from it but are weakened. The engineered ones, being immune, can drink their natural cousins under the table. "When fed on Plasmodium-infected blood, the transgenic malaria-resistant mosquitoes had a significant fitness advantage over wild-type," the researchers remarked in the Proceedings of the National Academy of Sciences. Thus, in an experiment in which the engineered mosquitoes began as 50 percent of the laboratory population, over the course of nine generations (several months) they grew to become 70 percent of the population.

Richard Tren, director of the group Africa Fighting Malaria, with offices in both South Africa and Washington, D.C., nevertheless cautions against over-enthusiasm. The mosquito work "is great research," he told me, but notes that what works beautifully in the lab may not work in the field for reasons we can't even guess at now. Further, he observes, "The research was done on a mosquito mostly found in Southeast Asia, Anopheles stephensi, and not in the more aggressive sub-Saharan African mosquito that spreads malaria called Anopheles gambiae." He also worries about whether it would be possible to introduce a large enough number of the engineered mosquitoes to squeeze out the natural population. But his greatest fear is that people "will get the idea this is a magic bullet." Even if all goes well, it may not be ready for prime time for ten years or more - or to measure it another way, 13 million deaths.

Tren calls for a holistic approach in fighting the disease. That includes full rehabilitation of the use of the insecticide DDT. "We're inching towards a vaccine," he told me, one that also will be genetically engineered. But he notes malaria vaccine research has been going on for many decades and "it seems like we're always just seven years away." Says Tren, "During the time we're waiting on this mosquito research it could be distracting from things that are already proved. This is a really complex disease and we need a range of interventions."

Don Roberts agrees. Roberts is a professor of tropical public heath at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. The engineered mosquito "is interesting research and an advancement of the science," he says. But among the problems is that even within anopheles gambiae there are an almost infinite genetic variety of mosquitoes. "A population of mosquitoes is a result of evolutionary force," he told me. "Just go downstream and you'll find a population that is different." He supports the biotech mosquito and vaccine research but says the emphasis for now must be insecticides, to include DDT but not to exclude developing others that may be far more effective.

"If you look at the amount of money going into a vaccine, it's probably in the billions" Roberts says. "Look into what's gone in to drugs to treat malaria and that's probably in the tens of billions. Then there's the environmentalist fight against DDT, which has probably also consumed billions of dollars," he notes. "But how much is being spent on an insecticide that would be less controversial and yet could be more effective at killing mosquitoes than DDT? Zero." He adds, "For me, it's a failure that's almost breathtaking."

So bring on the mosquito research and vaccine research. But for now and in the indefinite future the best weapon we have against this vicious mass-murderer of a disease is old-fashioned insecticide. Low-tech works now and we cannot afford to wait.



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

Trans fats:

For one summary of the weak science behind the "trans-fat" hysteria, see here. Trans fats have only a temporary effect on blood chemistry and the evidence of lasting harm from them is dubious. By taking extreme groups in trans fats intake, some weak association with coronary heart disease has at times been shown in some sub-populations but extreme group studies are inherently at risk of confounding with other factors and are intrinsically of little interest to the average person.