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Wednesday, October 22nd 2008

6:47 PM

Gene study turns up 26 lung cancer genes

A broad analysis of genes has turned up 26 mutations linked with the most common form of lung cancer, several of which play a role in other cancers as well, researchers said on Wednesday.

The findings, published in the journal Nature, double the number of genes already linked with lung adenocarcinoma, a type of non-small cell lung cancer that accounts for 40 percent of the more than 1 million lung cancer deaths each year.

"We think that our study may achieve a real impact on the cure of lung cancer patients," Dr. Matthew Meyerson of the Broad Institute of Massachusetts Institute of Technology and Harvard University said in a telephone briefing.

Meyerson was part of an international team that decoded 623 genes from tumors in 188 lung cancer patients and compared these to genes from normal tissues from the same people.

They found 26 genes that were most commonly altered in the tumors, most of which had never been linked with lung cancer. Some had been found in other types of tumors.

The new genes included mutations in neurofibromatosis 1, a gene known to cause a rare neurological disorder and raise the risk of nerve and brain tumors; ataxia telengiectasia mutated or ATM, which has ties with leukemia and lymphoma; retinoblastoma 1, which is linked with a rare childhood cancer of the eye; and adenomatosis polyposis coli or APC, which is common in colon cancer.

Many of the mutated genes also share common biological pathways or gene networks.

"Looking at the pathways helps simplify the picture," said Richard Wilson of Washington University in St. Louis, who helped lead the project.

PROMISING DRUGS

One of the most promising of these pathways is the mitogen-activated protein kinase or MAPK pathway, altered in more than 70 percent of the tumors. Drug compounds called MEK inhibitors that affect this pathway have already shown promise in mice with lung cancer.

About half of the tumors had defects in the p53 pathway, which is critical for suppressing tumor growth. Companies such as Introgen Therapeutics Inc (INGN.O: Quote, Profile, Research, Stock Buzz) are working on drugs that affect this pathway.

Some 30 percent of the tumors had mutations in the mTOR pathway, raising hope that drugs that inhibit the mTOR protein might help some lung cancer patients. Swiss drugmaker Novartis' (NOVN.VX: Quote, Profile, Research, Stock Buzz) mTOR inhibitor for kidney cancer, Afinitor, is currently under review by U.S. regulators.

The researchers also saw that a familiar class of genes known as tyrosine kinases, which trigger cell growth, played a key role in lung tumors. Gene families in this group include EGFR and VEGF.

Genentech (DNA.N: Quote, Profile, Research, Stock Buzz) and Roche Holding AG's (ROG.VX: Quote, Profile, Research, Stock Buzz) drug Avastin targets VEGF, while their pill for advanced lung cancer called Tarceva interferes with EGFR. A recent study found combining the two did little to help lung cancer patients live any longer.

Meyerson said genetic testing may help determine which patients might benefit from current drugs, but he said many new drugs will likely come from the findings as well.

"Probably, we will need a lot more drugs. What's great is we've identified many new drug targets," he said.

Some analysts predict the market for non-small cell lung cancer could exceed $4 billion between 2010 and 2015.

Julie Steenhuysen


Food Allergy in Kids Up 18%


CDC: 4% of U.S. Children Now Suffer Food Allergies
Child food allergies are up 18% over the last decade, the CDC reports.

Four out of every 100 U.S. kids under age 18 now suffer food allergies, which doubles their risk of asthma and triples their risk of skin or respiratory allergies.

"It is a significant trend -- food allergies do appear to be continuously increasing over the decade," CDC health statistician Amy Barnum, MSPH , tells WebMD. "And if you look at hospital discharges with any diagnosis related to food allergy, there has been a significant increase."

The new CDC data confirms what pediatricians and allergists have been suspecting, says Hugh Sampson, MD, director of the Jaffe Food Allergy Institute at Mount Sinai Hospital, New York.

"There was the impression food allergy is increasing in children, but we only had data on peanut allergy," Sampson tells WebMD. "This report shows it is food allergy in general. That goes along with what a lot of pediatric allergists and pediatricians have been thinking."

Eight types of food account for 90% of food allergies, the CDC finds:

  • Milk
  • Eggs
  • Peanuts
  • Tree nuts
  • Fish
  • Shellfish
  • Soy
  • Wheat

Why are our more and more American kids allergic to foods? Nobody knows for sure, Sampson says. But one clue comes from the fact that peanut allergies are up not just in the U.S., but in other nations that eat the same way we do.

"This seems to be primarily a phenomenon of Westernized countries, among people who have our kind of lifestyle and our kind of diet. You don't see similar things in countries in Asia or in Africa," he notes.

For example, Sampson says, children in China eat just as much peanut-based food as U.S. children do. But peanut allergy is almost unheard of in China.

"We eat peanuts dry roasted, and they eat them boiled or fried," Sampson notes. "The high temperature of dry roasting does make peanuts accrue changes that make them more allergenic."

Most food allergies develop in the first years of life. Milk and egg allergies tend to occur before a child's first birthday. Sampson suggests that the CDC numbers -- based on food allergies in the last year in kids up to 18 years old -- may actually underestimate the prevalence of food allergies in very young children.

"There was a study suggesting that 6% to 8% of kids up to age 3 years had some form of food allergy. Then by age 10 it drops down to about 4%, which corresponds with the number the CDC has come up with," Sampson notes.

Food allergy is different from food intolerance. An allergic reaction is a haywire immune response to what should be a harmless substance. Food intolerance is the inability to digest or to metabolize food.

Sampson says kids who develop food allergies usually get a skin rash or hives. With more severe cases, there may be vomiting or difficulty breathing. A child with food intolerance usually has a stomachache, bloating, and/or diarrhea.

Food allergies can be very serious.

"I would never ignore a rash. At a minimum, contact a pediatrician," Sampson says. "And we know that children who develop a milk allergy are at risk of another allergy. We see that kids with milk allergy get other allergic symptoms, like asthma, much more often than kids without food allergies."

Indeed, the CDC finds:

  • 29% of kids with food allergies, but only 12% of kids without food allergies, also have asthma.
  • 27% of kids with food allergies, but only 8% of kids without food allergies, also have eczema or skin allergy.
  • More than 30% of kids with food allergies, but only 9% of kids without food allergies, also have respiratory allergies.

The CDC data come from two sources: the National Health Interview Survey, which sampled some 9,500 children in 2007; and the National Hospital Discharge Survey, which includes 270,000 inpatient records from about 500 hospitals.

The CDC report, "Food Allergy Among U.S. Children: Trends in Prevalence and Hospitalizations," was released on Oct. 22.

Daniel J. DeNoon
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