Risky pregnancy drug raised daughters' cancer odds (AP)

A drug that millions of pregnant women took decades ago to prevent miscarriage and complications has put their daughters at higher risk for breast cancer and other health problems that are showing up now, a new federal study finds.

Many of these daughters, now over 40, may not even know of their risk if their mothers never realized or told them they had used the drug, a synthetic estrogen called DES.

The new study suggests that infertility is twice as common and that breast cancer risk is nearly doubled in these daughters.

Debbie Wingard is one of them. The 59-year-old San Diego woman adopted two boys after being unable to conceive and has had breast cancer twice � when she was 39 and 49.

"There's no knowing what's going to happen as we age. There's always the fear there's going to be another cancer or another outcome," she said. "I don't think I'll ever get to the point where I feel it's behind me."

The sons of DES users also face health risks � testicular problems and cysts � but these are less well studied and don't seem to be as common. Even less is known about the third generation � "DES grandchildren." Some research suggests these girls start menstruating late and have irregular periods, possible signs of fertility issues down the road.

In the United States alone, more than 2 million women and 2 million men are thought to have been exposed to DES while in the womb and may now want to talk with their doctors about when they should be screened for health problems.

"We don't want to cause a panic of everyone rushing out thinking they're going to get cervical or breast cancer. They just need to have that conversation with their physician," said Dr. Sharmila Makhija, women's health chief at the University of Louisville.

The average woman has about a 1 in 50 chance of developing breast cancer by age 55; for DES daughters it's 1 in 25, the study found. Risks for other health problems vary.

DES, or diethylstilbestrol, was widely used in the United States, Europe and elsewhere from the 1940s through the 1960s to prevent miscarriage, premature birth, bleeding and other problems. Many companies made and sold it as pills, creams and other forms.

Studies later showed it didn't work. The government told doctors to stop using it in pregnancy in 1971, after DES daughters in their late teens and 20s were found to be at higher risk of a rare form of vaginal cancer. Further research has tied DES to infertility and various pregnancy problems.

"They've been identified one at a time. Nobody's been able to get the whole picture," said Dr. Robert Hoover, a researcher at the National Cancer Institute. The new study, which he led, "takes the woman and looks at everything that can happen as a result of this drug," and adds evidence for some previously suspected risks like breast cancer, he said.

Results are in Thursday's New England Journal of Medicine.

The study started in 1992 and involved about 4,600 DES daughters and a comparison group of 1,900 similar women whose mothers had not used DES. Their health was tracked over time through surveys and medical records. Their average age at the last followup was 48.

In the study, researchers found these rates of health problems in DES daughters compared to non-exposed women:

_Breast cancer, 3.9 percent versus 2.2 percent.

_Cervical pre-cancer, 6.9 percent versus 3.4 percent.

_Infertility, 33.3 percent versus 15.5 percent.

_Early menopause, 5.1 percent versus 1.7 percent

These complications were seen among women who were able to become pregnant:

_Preterm delivery, 53.3 percent versus 17.8 percent.

_Miscarriage, 50.3 percent versus 38.6 percent.

_Tubal pregnancy, 14.6 percent versus 2.9 percent.

_Stillbirth, 8.9 percent versus 2.6 percent.

_Preeclampsia (high blood pressure during pregnancy), 26.4 percent versus 13.7 percent.

The claim of added breast cancer risk is being tested by 53 women in a lawsuit against DES makers under way now in Boston. One of them is Jackie White, 48, who lives in Centerburg, Ohio, north of Columbus. She said she had a misshaped uterus and reproductive problems, and found a lump last year that turned out to be breast cancer. Tests showed 20 tumors in one breast, two pre-cancers in the other and spread to her lymph nodes.

"I ate a low-fat diet. I exercise faithfully so I was not overweight. I had none of the normal risk factors," she said.

When and how often to screen women for breast cancer is the subject of much debate. A government task force recommends that women at average risk of breast cancer get mammograms every other year starting at age 50, and talk to their doctors about screening before then. Many medical groups urge starting at age 40.

DES exposure needs to be considered with the whole picture of a woman's risk, said Dr. G. Wright Bates, director of reproductive medicine at the University of Alabama at Birmingham.

"In some cases, frequent Pap smears and early mammography or breast MRI may be warranted for women with DES exposure," he said.

Others are focused on possible risks to the next generation.

Sally Keely, who was part of the federal study, and her husband are both offspring of women who took DES during pregnancy. Keely, 49, of Kalama, Wash., had miscarriages and a tubal pregnancy and required fertility treatments to have a daughter, now 9.

"I would like to push for more funding on the third generation exposed so I would know best how to advise my daughter," she said.

Fran Howell, executive director of DES Action USA, an advocacy group based in Jupiter, Fla., adopted a daughter, now 20, after being unable to conceive.

"So many of the DES daughters worry about problems with their children," she said. "The DES ends with me."

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Online:

Cancer Institute: http://www.cancer.gov/cancertopics/factsheet/Risk/DES.

CDC: http://www.cdc.gov/des/consumers/about/concerns_daughters.html

Advocacy group: http://www.desaction.org

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Marilynn Marchione can be followed at http://twitter.com/MMarchioneAP

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CDC: Self-reported drunk driving is down (AP)

ATLANTA � Health officials say drunken driving has fallen 30 percent in five years, and last year was at its lowest mark in nearly two decades.

The Centers for Disease Control and Prevention study, released Tuesday, is based on a 2010 national telephone survey of U.S. adults. About 1 in 50 said they'd driven drunk at least once in the previous month. Some said they did it daily.

That led to a CDC estimate of more than 112 million episodes of drunk driving in 2010. But that's down from the 161 million incidents in the peak year of 2006.

Other research suggests people drink heavily as much as in years past. CDC officials think more people may now drink at home, perhaps because of the economy.

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Online:

CDC report: http://www.cdc.gov/vitalsigns

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Cervical cancer virus fuels oral cancer type, too (AP)

WASHINGTON � A prolonged sore throat once was considered a cancer worry mainly for smokers and drinkers. Today there's another risk: A sexually transmitted virus is fueling a rise in oral cancer.

The HPV virus is best known for causing cervical cancer. But it can cause cancer in the upper throat, too, and a new study says HPV-positive tumors now account for a majority of these cases of what is called oropharyngeal cancer.

If that trend continues, that type of oral cancer will become the nation's main HPV-related cancer within the decade, surpassing cervical cancer, researchers from Ohio State University and the National Cancer Institute report Monday.

"There is an urgency to try to figure out how to prevent this," says Dr. Amy Chen of the American Cancer Society and Emory University, who wasn't part of the new research.

While women sometimes get oral cancer caused by the HPV, the risk is greatest and rising among men, researchers reported in the Journal of Clinical Oncology. No one knows why, but it begs the question of whether the vaccine given to girls and young women to protect against cervical cancer also might protect against oral HPV.

HPV vaccination is approved for boys to prevent genital warts and anal cancer, additional problems caused by human papillomavirus. But protection against oral HPV hasn't been studied in either gender, says Dr. Maura Gillison, a head-and-neck cancer specialist at Ohio State and senior author of the new research. That's important, because it's possible to have HPV in one part of the body but not the other, she says.

A spokeswoman for Merck & Co., maker of the HPV vaccine Gardasil, said the company has no plans for an oral cancer study.

Monday's research was funded by the NCI and Ohio State. Gillison has been a consultant to Merck.

There are nearly 10,000 new cases of oropharyngeal cancer a year, and overall incidence has risen by 28 percent since 1988 even as other types of head-and-neck cancer have been declining.

Tobacco and alcohol have long been the main causes of these tumors, which occur in the tonsils, base of the tongue and upper throat. But over the past few years, studies have shown HPV is playing a role in that rise, probably due to an increase in oral sex even as tobacco use was dropping.

The new study took a closer look, tracking HPV over time by directly testing tumor tissue from 271 patients that had been stored in cancer registries in Hawaii, Iowa and Los Angeles. The proportion that were HPV-positive rose from just 16 percent in the late 1980s to nearly 73 percent by the early 2000s.

Translate that to the overall population, and the researchers concluded that incidence rates of the HPV-positive tumors more than tripled while HPV-negative tumors dropped by half.

Oral cancer has always been a bigger threat to men than women. Gillison says women account for only about 1 in 4 cases, and their incidence is holding steady while men's is rising. That raises questions about gender differences in sexual behavior or whether oral HPV infection is likely to linger longer in men.

While HPV is the most common sexually transmitted infection, studies show women's bodies usually clear the virus from the cervix quickly; only an infection that persists for years is a cancer risk. It's not known if oral HPV acts similarly or even is as common.

Nor is it clear if oral sex is the only way it's transmitted, cautions Dr. Gregory Masters of the American Society for Clinical Oncology, an oncologist at Delaware's Helen Graham Cancer Center.

Regardless, just over 11,000 cases of cervical cancer will be diagnosed this year, a number that has been dropping steadily thanks to better Pap smears. (It's too soon to know what difference vaccination will make.) Gillison's team calculated that annual cases of cervical cancer will drop to 7,700 by 2020 � compared with about 8,700 cases of HPV-positive oropharyngeal cancer by then, about 7,400 of them in men.

The cancer society's Chen urged caution about those numbers, saying more data is needed. But she says two things are clear: First, patients with HPV-linked oral tumors have better survival odds than those with other types of this cancer, possibly because they tend to be younger. Studies are beginning to test if they can scale back today's treatment and thus suffer fewer long-term side effects such as problems with speech and swallowing.

And "just because you're not a smoker or drinker doesn't mean you can't get throat cancer," Chen says � so get checked for symptoms like a throat that's sore for longer than two weeks.

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EDITOR'S NOTE � Lauran Neergaard covers health and medical issues for The Associated Press.

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Scientist wins Nobel for medicine days after death (AP)

STOCKHOLM � A pioneering cell biologist was awarded the Nobel Prize in medicine Monday for his discoveries about the immune system. Hours later, his university said he had died of pancreatic cancer three days earlier, even as he was using his own research to try to save his life.

The Nobel committee, which is only supposed to consider living scientists, said it was unaware of the death of Ralph Steinman when it awarded the 10 million kronor ($1.5 million) prize.

The Nobel statutes say work "by a person since deceased shall not be considered for an award" but they don't specifically say whether that also applies if the jury mistakenly picks a winner unaware that he or she has died.

"I think you can safely say that this hasn't happened before," Nobel Foundation spokeswoman Annika Pontikis told The Associated Press. The committee was expected to make a statement on the issue later Monday.

The Canadian-born Steinman, 68, who shared the prize with American Bruce Beutler and French scientist Jules Hoffmann, died Sept. 30 of pancreatic cancer, according to Rockefeller University in New York, where he had studied and worked since 1970.

It said Steinman underwent therapy based on his discovery of the immune system's dendritic cells, for which he won the prize.

"He was diagnosed with pancreatic cancer four years ago, and his life was extended using a dendritic-cell based immunotherapy of his own design," the university said.

Beutler and Hoffmann were cited for their discoveries in the 1990s of receptor proteins that can recognize bacteria and other microorganisms as they enter the body, and activate the first line of defense in the immune system, known as innate immunity.

Nobel committee members said the work by the three is being used to develop better vaccines, and in the long run could also help treatment of diseases linked to abnormalities in the immune system, such as rheumatoid arthritis, Type 1 diabetes, multiple sclerosis and chronic inflammatory diseases.

The work could also help efforts to make the immune system fight cancerous tumors, the committee said.

No vaccines are on the market yet, but Nobel committee member Goran Hansson told The Associated Press that vaccines against hepatitis are in the pipeline.

"I am very touched. I'm thinking of all the people who worked with me, who gave everything," Hoffmann said by telephone to a news conference in Paris. "I wasn't sure this domain merited a Nobel."

Beutler said he woke up in the middle of the night, glanced at his cellphone and realized he had a new email message.

"And, I squinted at it and I saw that the title line was 'Nobel Prize,' so I thought I should give close attention to that," Beutler said in an interview posted on the Nobel website. "And, I opened it and it was from Goran Hansson, and it said that I had won the Nobel Prize, and so I was thrilled."

Still, he was a "little disbelieving" until he checked his laptop, "and in a few minutes I saw my name there and so I knew it was real."

Since 1974, the Nobel statutes don't allow posthumous awards unless a laureate dies after the announcement but before the Dec. 10 award ceremony. That happened in 1996 when economics winner William Vickrey died a few days after the announcement.

Before the statutes were changed in 1974 two Nobel Prizes were given posthumously. In 1961, U.N. Secretary-General Dag Hammarskjold was awarded the Nobel Peace Prize less than a month after he died in a plane crash during a peace mission to Congo. Swedish poet Erik Axel Karlfeldt won the Nobel in literature in 1931, although he had died in March of that year.

Hansson said the medicine committee didn't know Steinman was dead when it chose him as a winner and was looking through its regulations.

"It is incredibly sad news," he said. "We can only regret that he didn't have the chance to receive the news he had won the Nobel Prize. Our thoughts are now with his family."

Beutler, 53, holds dual appointments at University of Texas Southwestern Medical Center in Dallas and as professor of genetics and immunology at the Scripps Research Institute in San Diego. He will become a full-time faculty member at UT Southwestern on Dec. 1.

Hoffmann, 70, headed a research laboratory in Strasbourg, France, between 1974 and 2009 and served as president of the French National Academy of Sciences between 2007-08.

Steinman had been head of Rockefeller University's Center for Immunology and Immune Diseases.

"We are all so touched that our father's many years of hard work are being recognized with a Nobel Prize," Steinman's daughter, Alexis Steinman, said in the Rockefeller University statement. "He devoted his life to his work and his family, and he would be truly honored."

Hoffmann's discovery came in 1996 during research on how fruit flies fight infections. Two years later, Beutler's research on mice showed that fruit flies and mammals activate innate immunity in similar ways when attacked by germs.

Steinman's discovery dates back to 1973, when he found a new cell type, the dendritic cell, which has a unique capacity to activate T-cells. Those cells have a key role in adaptive immunity, when antibodies and killer cells fight infections. They also develop a memory that helps the immune system mobilize its defenses next time it comes under a similar attack.

The medicine award kicked off a week of Nobel Prize announcements, and will be followed by the physics prize on Tuesday, chemistry on Wednesday, literature on Thursday and the Nobel Peace Prize on Friday. The winners of the economics award will be announced on Oct. 10.

The coveted prizes were established by wealthy Swedish industrialist Alfred Nobel � the inventor of dynamite � except for the economics award, which was created by Sweden's central bank in 1968 in Nobel's memory. The prizes are always handed out on Dec. 10, on the anniversary of Nobel's death in 1896.

Last year's medicine award went to British professor Robert Edwards for fertility research that led to the first test tube baby.

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Associated Press writer Malin Rising contributed to this report.

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Calif. gov signs bill to prevent circumcision bans (AP)

SACRAMENTO, Calif. � California's governor has signed a bill that that will prevent local governments from banning male circumcision.

Gov. Jerry Brown's office announced Sunday that the Democrat signed AB768, a bill written in response to a ballot measure proposed in San Francisco.

Backers of a ban collected more than 7,700 signatures to put a measure on the November ballot in San Francisco to outlaw the circumcision of most male children. It was later blocked by a judge.

They had argued that circumcision is an unnecessary surgery that can lead to sexual and health problems later in life.

Those against the ban say it is an important religious practice for many Jews and Muslims, and that it can reduce the risk of cancer and sexually transmitted diseases.

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Long road from farm to fork worsens food outbreaks (AP)

WASHINGTON � Outbreaks of listeria and other serious illnesses linked to tainted food are becoming more common, partly because much of what we eat takes a long and winding road from farm to fork.

A cantaloupe grown on a Colorado field may make four or five stops before it reaches the dinner table. There's the packing house where it is cleaned and packaged, then the distributor who contracts with retailers to sell the melons in large quantities. A processor may cut or bag the fruit. The retail distribution center is where the melons are sent out to various stores. Finally it's stacked on display at the grocery store.

Imported fruits and vegetables, which make up almost two-thirds of the produce consumed in the United States, have an even longer journey.

"Increasingly with agribusiness you have limited producers of any given food, so a breakdown in a facility or plant or in a large field crop operation exposes thousands because of the way the food is distributed," says Dr. Brian Currie, an infectious disease specialist at Montefiore Medical Center in New York.

The Colorado cantaloupe crop that's linked to 84 illnesses and as many as 17 deaths in 19 states has traveled so far and wide that producer Jensen Farms doesn't even know exactly where their fruit ended up.

The company said last week that it can't provide a list of retailers that sold the tainted fruit because the melons were sold and resold. It named the 28 states where the fruit was shipped, but people in other states have reported getting sick.

A Kansas-based processor that purchased cantaloupes from Jensen, Carol's Cuts, didn't provide a notice to its customers that it had sold the farm's cantaloupes until nine days after the original recall.

"The food chain is very complex," says Sherri McGarry, a senior adviser in the Food and Drug Administration's Office of Foods. "There are many steps, and the more steps there are the harder it can be to link up each step to identify what the common source" of an outbreak is.

Fewer and larger farms and companies dominate food production in the country. That has driven some consumers to seek out farmers markets and locally grown produce. Supermarkets now highlight food grown nearby, while farmers markets have soared in popularity.

But many in the produce industry have come together to try and improve the ability to quickly trace food from field to plate.

This is good business. Large recalls, such as spinach in 2006, peanuts in 2009 and eggs in 2010, tend to depress sales for an entire product industry, even if only one company or grower was responsible for the outbreak.

Recent outbreaks of salmonella in peanuts and eggs, which are ingredients in thousands of foods, have been more widespread and sickened more people than have the tainted cantaloupe.

"There has been a laser focus on improving traceability so any recall can identify the affected product immediately and not have an effect on the rest of the entire category," says Ray Gilmer of United Fresh Produce Association, which represents the country's largest growers.

Gilmer says that larger food companies have no choice but to take food safety very seriously.

"The stakes for a large company to have a food safety incident are huge," he said. "It could destroy their company."

Listeria, a bacteria found in soil and water, often turns up in processed meats because it can contaminate a processing facility and stay there for a long period of time. It's also common in unpasteurized cheeses and unpasteurized milk, though less so produce such as cantaloupe.

The disease can cause fever, muscle aches, gastrointestinal symptoms and even death. One in five people who have listeria can die.

A food safety law passed by Congress last year gives the FDA new power to improve tracing food through the system. Food safety advocates say the law will help make the food network safer by focusing on making every step in the chain safer and making it easier to find the source of outbreaks.

For the first time, larger farms are required to submit plans detailing how they are keeping their produce safe.

Erik Olson, director of food and consumer safety programs for the Pew Health Group, says it is critical that those improvements are made to prevent more, larger outbreaks as the system grows more complex.

"Clearly the food industry has just changed enormously in the last several decades," Olson said. "It would be virtually impossible to sit down and eat a meal and eat food that hasn't come from all over the world."

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Online:

Centers for Disease Control and Prevention: http://www.cdc.gov/listeria/index.html

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