Cancer-causing substances update

For the first time, the US government has added certain viruses to its list of things that can cause cancer in humans. Hepatitis B, hepatitis C, and some human papilloma viruses (HPV) are among the 17 new entries on the Department of Health and Human Services' Eleventh Edition of the Report on Carcinogens.

The list, which is updated every two years, now details 58 substances that are known to cause cancer in humans, and 188 substances "reasonably anticipated" to do so.

Six new known carcinogens were added in the latest update. Hepatitis B and C were included because they cause liver cancer. Several types of HPV cause cervical cancer.

"These viruses are important causes of cancer," said Elizabeth Ward, PhD, director of surveillance research for the American Cancer Society.

The most recent ACS report on cancer in the US, Cancer Facts & Figures 2005, highlighted these and several other cancer-causing viruses because of their impact on cancer worldwide.

The report estimates that there will be 667,000 new cases of liver cancer worldwide in 2005. Of those, 35% will be caused by chronic infection with hepatitis B and 23% will be caused by chronic infection with hepatitis C. HPV is considered the main cause of the 490,000 new cases of cervical cancer that occur worldwide each year.

Gamma radiation and X-rays were also added to the list of known carcinogens because they can cause leukemia and cancers of the thyroid, breast, and lung, as well as other types of cancer. Most people are exposed to this type of radiation from medical procedures or by exposure to natural sources like radon, a gas that filters up through the ground. Radiation from neutrons, which penetrates the Earth's atmosphere from space, is also now part of this list. Neutron radiation causes genetic damage similar to that caused by x-rays and gamma rays and can cause the same types of cancer.

Lead, Meat Compounds, Industrial Chemicals Suspect

Most of the 11 new substances added to the list of things that probably cause cancer are chemicals used in industrial processes or manufacturing. These substances -- naphthalene, cobalt sulfate, nitrobenzene, nitromethane, and the dye ingredients 1-amino-2, 4-dibromoanthraquinone and 4,4-thiodianiline -- have been shown to cause cancer in animals. Another dye compound, diazoaminobenzene, causes genetic damage in animals. In the human body, it changes into benzene, a substance known to cause cancer in people.

The other new substances on this list, however, are more commonly found throughout the environment. Lead is now officially considered a compound that might cause cancer in people because it is known to cause kidney, brain, and lung cancer in animals. Lead is used to make some batteries, ammunition, and cable coverings, and may be found in paints, glass, ceramics, fuels, and even some cosmetics. People are exposed to lead by swallowing or breathing it.

"In years past, when lead was added to gasoline, this was the major source of exposure," Ward explained. "More recently, since lead has been taken out of gasoline, the major source of exposure has been old lead-containing paint, which can be found in older homes and on structures such as bridges."

Although the amount of lead used in paint has been regulated since 1979, Ward said, millions of homes in the United States still have lead paint. During renovation of an older home, swallowing or breathing lead paint dust can increase your body’s lead content. Children may chew or swallow chips of this old paint. More often, normal wear and tear adds particles of paint to soil and household dust, and children unintentionally swallow lead from their contaminated toys or hands.

Tap water that runs through lead pipes and soldered joints in older homes can also be contaminated with lead.

The US Environmental Protection Agency has information on testing your home for lead and getting it removed.

The final addition to the probable carcinogen list is a collection of compounds that form in meat when it is grilled or cooked at high temperatures. MeIQ, MeIQx, and PhIP are known as heterocyclic amine compounds; they can cause cancer in animals. Some studies suggest that consumption of meat cooked at high temperatures increases risk of colon cancer and breast cancer in humans.

Because of this link, ACS dietary guidelines recommend cooking meat at lower temperatures -- such as by baking, broiling, or poaching it -- rather than charbroiling or frying it.

"Although it is not possible to predict with complete certainty from animal studies which exposures will cause cancer in humans," Ward said, "it is prudent to treat substances that cause cancer in laboratory animals as if they pose a hazard to humans."

http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Viruses_Added_to_List_of_Cancer-Causing_Substances.asp

Altered HIV attacks mice tumors

Researchers at the University of California at Los Angeles have tweaked HIV to create a gene therapy that attacks cancer tumors in mice.

The research is a step forward for the beleaguered field of gene therapy, which has enjoyed isolated successes and suffered repeated setbacks over the past 20 years. But tinkering and fine tuning will be the key to a successful gene therapy, UCLA researchers believe. They published their study in the Feb. 13 issue of Nature Medicine.

The UCLA AIDS Institute scientists genetically altered HIV and folded it into an envelope made of another virus called sindbis, which typically infects insects and birds. That turned the altered HIV into a missile that hunted down metastasized melanoma cells in the lungs of living mice.

"People might wonder if it's scary to use HIV as a therapy," said Irving Chen, who led the UCLA team. "But in actuality we have completely removed 80 percent of the virus. So really it's just a carrier."

Other researchers have tried morphing HIV into a gene therapy, with limited results.

"This hasn't been possible before," Chen said. "Usually (researchers) take a virus and try to modify its own envelope, but it falls off or becomes so deformed it is not able to infect cells anymore."

The secret to the UCLA researchers' success was adding the sindbis cloak, Chen said. He and his colleagues suspected the virus might make an HIV gene therapy more stable, and the results of the study showed they were right.

The scientists also inserted a glowing firefly protein into the virus to track its progress. They used a light-detection "cooled charged-coupled device," or CCCD, camera to look at the glowing protein inside live mice. Because the protein was attached to the gene therapy, the researchers could see that the treatment had hit its mark.

The researchers programmed the altered virus package to attack a protein on the cancer cell surface called p-glycoprotein, which causes problems in cancer patients by shuttling cancer drugs away from the cell. In other words, p-glycoprotein causes resistance to cancer medication. Scientists could customize the system to target any protein on the surface of a cell, Chen said. He and his colleagues have seen success with about a dozen different molecules, including brain and other blood cells, he said.

More incremental work, with the goal of increasing the precision of the treatment and reducing the chance of side effects, is necessary before this type of gene therapy can be tested in humans, Chen said. In a premature human trial in 1999, 18-year-old Jesse Gelsinger died during a gene therapy clinical trial at the University of Pennsylvania, which led to an FDA investigation and closure of the Penn gene therapy program.

"I think one of the problems with gene therapy has been whenever people get a new approach they immediately go into patients," Chen said. "Our approach has been test in cell culture, then in mice. We're not planning any clinical trials until this is fully refined."

Kristen Philipkoski

http://www.wired.com/news/medtech/0,1286,66579,00.html

Family Link in Myeloma Patients?

J Clin Oncol. 2005 Feb 1;23(4):685-93.Lynch HT, Watson P, Tarantolo S, Wiernik PH, Quinn-Laquer B, Isgur BergsagelK, Huiart L, Olopade OI, Sobol H, Sanger W, Hogg D, Weisenburger D.Creighton University School of Medicine, 2500 California Plaza, Omaha,Nebraska 68178, USA.
htlynch@creighton.edu

PURPOSE: To describe a series of families with familial multiple myeloma(MM). Observations were used to generate hypotheses about the role of genetic factors, the mode of inheritance of these factors, and the association of other cancers with familial MM.

PATIENTS AND METHODS: This observational study consisted of 39 families with multiple cases of MM correlated disorders from four collaborating research centers. Each center followed its usual family study method. Probands were interviewed, and, when possible, cancers were verified by medical records and pathology review. A working pedigree was compiled on each family.

RESULTS: Seventeen families had affected members in two or more generations, and eight families had two or more affected members in a single generation. Four families had two or more members with plasma cell dyscrasias, with or without a single case of MM. In the remaining 10 families, a single MM case occurred with a family history of other cancers. Other cancers observed in family members included hematologic malignancies and solid tumors. In families with MM in multiple generations, there was a decrease in the age at MM diagnosis in successive generations.

CONCLUSION: The study of familial MM may provide insights into the pathogenesis and, ultimately, the control and prevention of MM and related disorders. Population-based epidemiologic studies are crucial, but because of the rarity of familial MM, a concerted case-finding approach may also be fruitful. Therefore, we propose an international consortium to study familial MM, and we invite all interested colleagues to participate.