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	Study questions heart protection from flavonoids Last Updated: 2007-05-22 13:03:44 -0400 (Reuters Health) By Amy Norton NEW YORK (Reuters Health) - Plant antioxidants called flavonoids may not offer the protection against heart disease that some research has suggested, according to a large study of U.S. women. Flavonoids are compounds found in fruits, vegetables, wine and tea that act as cell-protecting antioxidants. Lab studies have also found that they may inhibit blood clotting and maintain healthy blood vessel function, which in theory could lower a person's risk of heart disease. Studies in people have come to mixed conclusions, however. Some, but not all, have found that people with a relatively high flavonoid intake have a lower risk of heart disease. The new study, which followed more than 66,000 U.S. women, is much larger than most of those earlier studies. The results, reported in the American Journal of Epidemiology, show no link between a woman's overall intake of flavonoids and her risk of suffering a heart attack or dying of heart disease over the next 12 years. Article continues below and (thank you)
Still, the findings should not deter people from consuming flavonoid-rich foods, according to the study's lead author. Fruits and vegetables, tea and moderate amounts of wine remain good choices for overall health, Dr. Jennifer Hsiang-Ling Lin told Reuters Health. "These foods and beverages contain many important health-promoting nutrients, in addition to flavonoids," said Lin, of Brigham and Women's Hospital and Harvard Medical School in Boston. She and her colleagues based their findings on data from the Nurses' Health Study, which began in 1976, enrolling more than 120,000 female nurses between the ages of 30 and 55. Lin's team focused on 66,360 women who answered detailed questionnaires on their diet habits in 1990, 1994 and 1998. Based on those responses, the researchers were able to estimate study participants' intake of two major flavonoid subtypes -- flavonols and flavones. They found no association between the women's overall intake of these compounds in 1990 and their risk of suffering a heart attack or dying of heart disease over the next 12 years. There was one exception, however. Women who consumed higher amounts of a particular flavonol called kaempferol were less likely to die of heart disease than women with the lowest intakes. Kaempferol is found in foods such as tea and broccoli, and Lin's team found that women who ate the most broccoli had a relatively lower risk of dying from cardiovascular disease than their peers who shunned the vegetable. It's possible that among flavonoids, kaempferol has a particular cardiovascular benefit, according to Lin. For now, though, she said, the finding on kaempferol is an "interesting" one that warrants further study. SOURCE: American Journal of Epidemiology, June 1, 2007. Copyright © 2007 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
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Chemical Compounds Boost Breast Cancer Risk

By Alan Mozes
HealthDay Reporter

MONDAY, May 14 (HealthDay News) -- A detailed analysis of hundreds of completed breast cancer studies has linked disease development with environmental exposure to more than 200 chemical compounds.

The finding is part of an effort to build a free, online breast cancer database for researchers and the public.

Described as "the most comprehensive of its kind," the database will highlight growing concern about environmental carcinogens such as pollutants, food contaminants, and organic solvents. The scope of the project will also extend to work that explores risk-related lifestyle factors such as diet, levels of physical activity, smoking/drinking habits and body mass.

"This compilation is a great effort, because it summarizes all the evidence and gives us hints of what to look for next," explained researcher Leslie Bernstein, a professor of preventive medicine with the Keck School of Medicine at the University of Southern California in Los Angeles.

The results are outlined in a supplement to the May 14th online issue of Cancer. The database is already accessible at either www.silentspring.org/sciencereview or www.komen.org/environment.

According to the American Cancer Society (ACS), carcinogens are defined as agents that instigate abnormal cell division or harmful changes in the structure of a cell's DNA. They include chemicals, radiation, or infectious agents, among other things.

The ACS also notes that with the exception of skin cancer, breast cancer is the most common cancer among American women. This year, almost 179,000 women in the United States will be diagnosed with the disease, and about 40,000 will die.

The International Agency of Research on Cancer has already classified 90 or so compounds as human carcinogens, according to the ACS. But Bernstein's team said that most of the chemicals to which people are routinely exposed have not undergone any testing for carcinogenic risk. An estimated 80,000 chemicals are registered in the United States for commercial use, according to the researchers.

For more than two years, Bernstein worked alongside colleagues from Harvard University, the Roswell Park Cancer Institute, and the Silent Spring Institute to amass and sort through approximately 900 national and international breast cancer studies focused on carcinogens.

The team honed in on 460 human breast cancer studies, of which more than 150 looked at specific environmental carcinogens among breast cancer patients. Most of those studies were conducted in the 1990s.

The remaining studies involved animal or laboratory research. The researchers pointed out that animal studies are valid references, because all known human carcinogens have also triggered tumors in animal subjects.

In the animal studies alone, evidence surfaced that linked 216 chemicals to the onset of breast tumors. These included 36 industrial chemicals, 6 chlorinated solvents, 18 products of combustion, 10 pesticides, 18 dyes, four type of radiation, 47 pharmaceuticals, and 17 hormones.

Of these compounds, the researchers isolated 73 that can be found in either human food or consumer products.

They noted, for example, the lingering hazards associated with polychlorinated biphenyls (or PCBs), which were typically used in the production of electrical equipment until federally banned in 1979. PCBs continue to pose a risk via contaminated rivers, fish, and pre-existing building construction, the researchers warned.

In addition, the authors categorized 35 compounds as carcinogenic air pollutants, including polycyclic aromatic hydrocarbons (or PAHs), which are byproducts of combustion.

The team also drew attention to another group of 25 organic compounds, including dioxins, which are produced by waste incineration and manufacturing. These carcinogenic chemicals are present in many American workplaces and place more than 5,000 women at an increased risk for breast cancer, the researchers said. These include women working in machine shops, dry cleaners, hairdressers, glass manufacturers, and aircraft maintenance facilities, all of which use harmful organic solvents.

Furthermore, among the identified carcinogens, 29 are produced in large amounts -- upwards of one million pounds or more per year.

The database project did not set strict guidelines as to how to limit exposure to carcinogens. But the authors said they encouraged research and government oversight into the problem. They advised that people do try and limit their exposure to PCB-contaminated fish, gasoline-generated air pollution, chlorinated tap water, non-stick coated cookware, and detergents containing fluorescent whiteners.

Just how carcinogenic, in terms of breast cancer risk, are these and other compounds on the list? The jury is still out on that question, Bernstein said.

"Women are terribly concerned about environmental causes of breast cancer," she said. "But it's really very difficult to study. Often the only way we've been able to look at some of these things is during occupational exposures or accidents -- what we usually call disasters."

"So, this work is a very useful tool for those of us who want to try to understand what we've missed in breast cancer. Now, it's up to us to do something with all this information," Bernstein said.

Janet Gray, a professor of psychology and the director of the program in science, technology and society at Vassar College in Poughkeepsie, N.Y., called the new database "an enormous contribution."

"Its greatest value is just the sheer comprehensive nature of the work, which allows both the public and researchers to have access to huge amounts of information in one place," she said. "I think this effort will really move us forward."

Known and Probable Carcinogens

Including Industrial Processes, Occupational Exposures, Infectious Agents, Chemicals, and Radiation)

What Is a Carcinogen?

Cancer is caused by abnormalities in a cell’s DNA (its genetic "blueprint"). These may be inherited from parents, or they may be caused by outside exposures to the body such as chemicals, radiation, or even infectious agents.

Substances that can cause changes that can lead to cancer are called carcinogens. Some carcinogens do not act on DNA directly, but lead to cancer in other ways, such as causing cells to divide at a faster rate, which could increase the chances that DNA changes will occur.

Carcinogens do not cause cancer in every case, all the time. Substances classified as carcinogens may have different levels of cancer-causing potential. Some may cause cancer only after prolonged, high levels of exposure. And for any particular person, the risk of developing cancer depends on many factors, including the length and intensity of exposure to the carcinogen and the person’s genetic makeup.

How Do We Determine if Something Is a Carcinogen?
Scientists get much of their data about whether something might cause cancer from laboratory (cell culture and animal) studies. Although it isn’t possible to predict with certainty which substances will cause cancer in humans based on animal studies alone, virtually all known human carcinogens that have been adequately tested produce cancer in lab animals. In many cases, carcinogens are first found to cause cancer in lab animals and are later found to cause cancer in people. Because there are far too many substances (natural and manmade) to test each one in lab animals, scientists use knowledge about chemical structure, other types of lab tests, and information about the extent of human exposure to select chemicals for testing.

Most studies of potential carcinogens expose the lab animals to doses that are higher than common human exposures. This is so that cancer risk can be detected in relatively small groups of animals. For most carcinogens, it is assumed that those that cause cancer at larger doses in animals will also cause cancer in people. Although it isn’t always possible to know the relationship between exposure dose and risk, it is reasonable for public health purposes to assume that lowering human exposure will reduce risk.

Another important way to identify carcinogens is through epidemiologic studies, which look at human populations to determine which factors might be linked to cancer. While these studies also provide useful information, they also have their limitations. Humans do not live in a controlled environment. People are exposed to numerous substances at any one time, including those they encounter at work, school, or home; in the food they eat; and the air they breathe. And it is usually many years (often decades) between exposure to a carcinogen and the development of cancer. Therefore, it can be very hard to single out any particular exposure as having a definite link to cancer.

By combining data from both types of studies, scientists are able to make an educated assessment of a substance’s cancer-causing ability. When the available evidence is compelling but not felt to be conclusive, the substance may be considered to be a probable carcinogen.

How Are Carcinogens Classified?

International Agency for Research on Cancer (IARC)

The most widely used system for classifying carcinogens comes from the IARC, which is part if the World Health Organization (WHO). In the past 30 years, the IARC has evaluated the cancer-causing potential of about 900 likely candidates, placing them into one of the following groups:

• Group 1: Carcinogenic to humans
• Group 2A: Probably carcinogenic to humans
• Group 2B: Possibly carcinogenic to humans
• Group 3: Unclassifiable as to carcinogenicity in humans
• Group 4: Probably not carcinogenic to humans

Perhaps not surprisingly, most of the agents are of probable, possible, or unknown risk. Only about 90 are classified as "carcinogenic to humans."

National Toxicology Program (NTP)

In the United States, the NTP releases the Report on Carcinogens about every 2 years. The NTP is formed from parts of several different government agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA).

The Report on Carcinogens (RoC) identifies 2 groups of agents:

• "Known to be human carcinogens"
• "Reasonably anticipated to be human carcinogens"

Unlike the IARC’s list, the RoC does not list substances that have been studied and found not to be carcinogens. Below are the lists of known and probable human carcinogens from both groups.

Known Human Carcinogens

International Agency for Research on Cancer (IARC)
"Carcinogenic to Humans" (Group 1)

Agents and Groups of Agents

• Aflatoxins (naturally occurring mixtures of)
• 4-Aminobiphenyl
• Arsenic and arsenic compounds (Note: This evaluation applies to the group of compounds as a whole and not necessarily to all individual compounds within the group)
• Asbestos
• Azathioprine
• Benzene
• Benzidine
• Beryllium and beryllium compounds
• N,N-Bis(2-chloroethyl)-2-naphthylamine (Chlornaphazine)
• Bis(chloromethyl)ether and chloromethyl methyl ether (technical-grade)
• 1,4-Butanediol dimethanesulfonate (Busulphan; Myleran)
• Cadmium and cadmium compounds
• Chlorambucil
• 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Methyl-CCNU; Semustine)
• Chromium [VI] compounds
• Cyclophosphamide
• Cyclosporin (ciclosporin)
• Diethylstilbestrol (DES)
• Epstein-Barr virus
• Erionite
• Estrogen therapy, postmenopausal
• Estrogens, nonsteroidal (Note: This evaluation applies to the group of compounds as a whole and not necessarily to all individual compounds within the group)
• Estrogens, steroidal (Note: This evaluation applies to the group of compounds as a whole and not necessarily to all individual compounds within the group)
• Ethylene oxide
• Etoposide in combination with cisplatin and bleomycin
• Formaldehyde
• Gallium arsenide
• Gamma radiation
• Helicobacter pylori (infection with)
• Hepatitis B virus (chronic infection with)
• Hepatitis C virus (chronic infection with)
• Herbal remedies containing plant species of the genus Aristolochia
• Human immunodeficiency virus type 1 (infection with)
• Human papillomavirus type 16
• Human papillomavirus type 18
• Human T-cell lymphotropic virus type I
• Melphalan
• 8-Methoxypsoralen (Methoxsalen) plus ultraviolet A radiation
• MOPP and other combined chemotherapy including alkylating agents
• Mustard gas (Sulfur mustard)
• 2-Naphthylamine
• Neutrons
• Nickel compounds
• Opisthorchis viverrini (infection with)
• Oral contraceptives, combined (Note: There is also conclusive evidence that these agents have a protective effect against cancers of the ovary and endometrium)
• Oral contraceptives, sequential
• Phosphorus-32, as phosphate
• Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes), as aerosols
• Radioiodines, short-lived isotopes, including iodine-131, from atomic reactor accidents and nuclear weapons detonation (exposure during childhood)
• Radionuclides, alpha-particle-emitting, internally deposited (Note: Specific radionuclides for which there is sufficient evidence for carcinogenicity to humans are also listed individually as Group 1 agents)
• Radionuclides, beta-particle-emitting, internally deposited (Note: Specific radionuclides for which there is sufficient evidence for carcinogenicity to humans are also listed individually as Group 1 agents)
• Radium-224 and its decay products
• Radium-226 and its decay products
• Radium-228 and its decay products
• Radon-222 and its decay products
• Schistosoma haematobium (infection with)
• Silica, crystalline (inhaled in the form of quartz or cristobalite from occupational sources)
• Solar radiation
• Talc containing asbestiform fibers
• Tamoxifen (Note: There is also conclusive evidence that this agent (tamoxifen) reduces the risk of contralateral breast cancer)
• 2,3,7,8-Tetrachlorodibenzo-para-dioxin
• Thiotepa
• Thorium-232 and its decay products, administered intravenously as a colloidal dispersion of thorium-232 dioxide
• Treosulfan
• Vinyl chloride
• X- and Gamma radiation

Mixtures

• Alcoholic beverages
• Analgesic mixtures containing phenacetin
• Areca nut
• Betel quid with tobacco
• Betel quid without tobacco
• Coal-tar pitches
• Coal-tars
• Mineral oils, untreated and mildly treated
• Salted fish (Chinese-style)
• Shale-oils
• Soots
• Tobacco products, oral tobacco products
• Wood dust

Exposure Circumstances

• Aluminum production
• Arsenic in drinking water
• Auramine, manufacture of
• Boot and shoe manufacture and repair
• Coal gasification
• Coke production
• Furniture and cabinet making
• Hematite mining (underground) with exposure to radon
• Involuntary smoking
• Iron and steel founding
• Isopropanol manufacture (strong-acid process)
• Magenta, manufacture of
• Painter (occupational exposure as a)
• Rubber industry
• Strong inorganic acid mists containing sulfuric acid (occupational exposure to)
• Tobacco smoking

National Toxicology Program (NTP) 11th Report on Carcinogens

"Known to Be Human Carcinogens"

• Aflatoxins
• Alcoholic Beverage Consumption
• 4-Aminobiphenyl
• Analgesic Mixtures Containing Phenacetin
• Arsenic Compounds, Inorganic
• Asbestos
• Azathioprine
• Benzene
• Benzidine
• Beryllium and Beryllium Compounds
• 1,3-Butadiene
• 1,4-Butanediol Dimethylsulfonate (busulfan, Myleran ®)
• Cadmium and Cadmium Compounds
• Chlorambucil
• 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU)
• bis(Chloromethyl) Ether and Technical-Grade Chloromethyl Methyl Ether
• Chromium Hexavalent Compounds
• Coal Tar Pitches
• Coal Tars
• Coke Oven Emissions
• Cyclophosphamide
• Cyclosporin A (Ciclosporin)
• Diethylstilbestrol (DES)
• Dyes Metabolized to Benzidine
• Environmental Tobacco Smoke
• Erionite
• Estrogens, Steroidal
• Ethylene Oxide
• Hepatitis B Virus
• Hepatitis C Virus
• Human Papilloma Viruses: Some Genital-Mucosal Types
• Melphalan
• Methoxsalen with Ultraviolet A Therapy (PUVA)
• Mineral Oils (Untreated and Mildly Treated)
• Mustard Gas
• 2-Naphthylamine
• Neutrons
• Nickel Compounds
• Oral Tobacco Products
• Radon
• Silica, Crystalline (Respirable Size)
• Solar Radiation
• Soots
• Strong Inorganic Acid Mists Containing Sulfuric Acid
• Sunlamps or Sunbeds, Exposure to
• Tamoxifen
• 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD); "Dioxin"
• Thiotepa
• Thorium Dioxide
• Tobacco Smoking
• Vinyl Chloride
• Ultraviolet Radiation, Broad Spectrum UV Radiation
• Wood Dust
• X-Radiation and Gamma Radiation

Probable Carcinogens

International Agency for Research on Cancer (IARC)
"Probably Carcinogenic to Humans" (Group 2A)

Agents and Groups of Agents

• Acrylamide
• Adriamycin
• Androgenic (anabolic) steroids
• Aristolochic acids (naturally occurring mixtures of)
• Azacitidine
• Benz[a]anthracene
• Benzidine-based dyes
• Benzo[a]pyrene
• Bischloroethyl nitrosourea (BCNU)
• 1,3-Butadiene
• Captafol
• Chloramphenicol
• a-Chlorinated toluenes (benzal chloride, benzotrichloride, benzyl chloride) and benzoyl chloride (combined exposures)
• 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)
• 4-Chloro-ortho-toluidine
• Chlorozotocin
• Cisplatin
• Clonorchis sinensis (infection with)
• Dibenz[a,h]anthracene
• Diethyl sulfate
• Dimethylcarbamoyl chloride
• 1,2-Dimethylhydrazine
• Dimethyl sulfate
• Epichlorohydrin
• Ethylene dibromide
• N-Ethyl-N-nitrosourea
• Etoposide
• Glycidol
• Human papillomavirus type 31
• Human papillomavirus type 33
• Indium phosphide
• IQ (2-Amino-3-methylimidazo[4,5-f]quinoline)
• Kaposi's sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV-8)
• Lead compounds, inorganic
• 5-Methoxypsoralen
• 4,4´-Methylene bis(2-chloroaniline) (MOCA)
• Methyl methanesulfonate
• N-Methyl-N´-nitro-N-nitrosoguanidine (MNNG)
• N-Methyl-N-nitrosourea
• Nitrogen mustard
• N-Nitrosodiethylamine
• N-Nitrosodimethylamine
• Phenacetin
• Procarbazine hydrochloride
• Styrene-7,8-oxide
• Teniposide
• Tetrachloroethylene
• ortho-Toluidine
• Trichloroethylene
• 1,2,3-Trichloropropane
• Tris(2,3-dibromopropyl) phosphate
• Ultraviolet radiation A
• Ultraviolet radiation B
• Ultraviolet radiation C
• Vinyl bromide
• Vinyl fluoride