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Environmental Factors & Cancer

Research Roundup

Lindsey, Heather

doi: 10.1097/01.COT.0000287822.71358.43
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Environmental factors, whether linked to lifestyle issues such as smoking and diet or exposure to carcinogens in the air and water, are thought to be linked to an estimated 80% to 90% of cancer cases, according to the National Cancer Institute.

One of the most recent events to raise concerns in the public eye about the environmental impact on carcinogenesis is the destruction of the World Trade Center, from which researchers are compiling data about a variety of health effects.

In separate research, investigators continue to study the link between environmental variables, including diet and chemical exposure, and the development of many types of cancer, including those of the lung, breast, and prostate.

Unknown Effects of the World Trade Center Disaster

The potential impact of the destruction of the World Trade Center (WTC) on cancer development remains largely unknown, with some researchers assessing that there is little risk of carcinogenesis, while others acknowledging that cancer development remains possible.

Michael Thun, MD, MS, the American Cancer Society's Vice President for Epidemiology and Surveillance Research, maintains that from what scientists know about environmental exposures to agents, there is a low probability that the destruction contributed to substantial cancer risk, whether now or in the future.

In contrast, Michael Liebman, PhD, Chief Scientific Officer at the Windber (PA) Research Institute, says that there is such a potential at some point because of exposure to chemicals generated by the buildings' collapse.

Researchers know that both acute and chronic exposure to various chemicals can have an impact on risk in different ways, he explained. “Fundamentally, we know some agents produce risk, but we don't know everything, and the chemicals released at the site were a heterogeneous mix.”

It wouldn't be surprising in the not too distant future to see the evidence of cancers or other diseases showing up, but we won't know for certain whether they are associated with World Trade Center exposures, Dr. Liebman said.

Challenges to Measuring Impact

The effect of the destruction on cancer development is very difficult to measure, Dr. Thun said.

One of the challenges of evaluating the environmental impact on the health of people at Ground Zero is the relatively very small population size, noted Zuo-Feng Zhang, MD, PhD, Professor of Epidemiology and Public Health and Co-director of the Environmental Genomics Program at UCLA's Jonsson Comprehensive Cancer Center.

Considering this small population, it will take a long time to fully identify the impact on health. The risk may be profound among individuals with genetic defects, he added.

“One of the biggest problems is that there are certain assumptions about what exposures occurred with the WTC incident,” he said. However, exposure was not being adequately surveyed or analyzed. Researchers don't know what all the potential exposures were, what chemical levels were, or how people's lungs were exposed to these chemicals.

“What scientists know about the exposures to chemicals at the WTC site is that there was roughly 90,000 liters of jet fuel that burned, dust from the crumbling structures that contained asbestos from insulation, fiberglass, and small amounts of lead,” said Dr. Thun, adding that other chemicals were generated during combustion. “We also know that actual exposures weren't measured when the event occurred.”

Some Data Available

In one analysis (PNAS 2004;101:11685-11688), the air levels of carcinogenic polycyclic aromatic hydrocarbons (PAHs) were evaluated.

The particulate air pollutants contained mutagenic and carcinogenic PAHs. The researchers, from the University of North Carolina School of Public Health and the Environmental Protection Agency, measured nine PAHs in 243 samples collected at or near Ground Zero from September 23, 2001, to March 27, 2002.

They found that because elevated PAH levels were transient, any elevation in cancer risk from PAH exposure should be very small among non-occupationally exposed residents of New York City. However, they concluded that high initial levels of PAHs may be associated with reproductive effects observed in the offspring of women who were, or became, pregnant shortly after September 11, 2001.

A study conducted by the CDC's National Institute for Occupational Safety and Health found that, overall, cleanup workers at the site did not experience exposure to asbestos and silica that exceeded OSHA limits, noted Dr. Thun. Even though the fires burned for a number of months, this timeframe is much shorter than most occupational exposure, which often occurs over 40 years of working, he explained.

Additionally, the New York City Department of Health and Mental Hygiene, the federal Agency for Toxic Substances and Disease Registry, and numerous academic institutions, public agencies, and community groups created the WTC Health Registry to collect data from people most directly exposed to the events of 9/11.

The registry hopes to follow up with people periodically over the next 20 years to track any changes in their physical or mental health.

Educating Patients & the Public

Physicians who treat individuals who believe their cancer may be linked to the World Trade Center disaster should do so with respect, Dr. Thun said. “There was a huge stress associated with the event, and stress has an effect on immune system.” But researchers don't yet know the full effect of stress on carcinogenesis.

Patients should understand that solid tumors tend to develop over decades, and consequently, if there was an impact on any recent development of solid tumors, it would have been in the late stages of carcinogenesis.

“It's not like Hiroshima, where people were exposed to a very high short-term dose of carcinogen,” Dr. Thun said. Most of the time, people experience a prolonged exposure to environmental carcinogens that last many decades.

Over the past 10 years, researchers have characterized the genetic changes that occur during a normal cell's transition to malignancy. The number of steps varies from cancer to cancer, but many solid tumors tend to have six or more, he said.

Leukemia and cancers that develop during childhood require fewer genetic changes, but there isn't a clear scientific link between the types of exposures generated by the World Trade Center destruction and childhood cancers.

The actual development of cancer due to environmental exposures is dependent on a variety of factors, not only including the chemicals involved, but also the individuals exposed and their underlying risk factors such as weight—for example, how fat stores and releases chemicals could be problematic, Dr. Liebman noted.

Additionally, different people will be more susceptible to exposures at different ages and stages of development and in a varying manner, a combination of factors that researchers don't yet understand.

Other Environmental Factors

Strides are being made in other areas, however, in determining what environmental factors, whether dietary or chemical, do have an impact on cancer development.

For example, Dr. Zhang and his colleagues are evaluating the impact of air pollution, smoking, and genetic defects on lung cancer risk.

“Different people respond to carcinogens differently,” Dr. Zhang said. This is why some heavy smokers may never develop lung cancer, while other individuals with no significant exposure to cigarette smoke may nonetheless develop lung cancer for genetic reasons.

Defects may occur in a series of genes. For example, damage may occur in genes that involve the metabolism of carcinogens or in genes that deal with the DNA-repair process.

According to several prospective studies, he noted, air pollution is moderately associated with increased lung cancer risk, but this risk is not as strong as tobacco smoking. The relative risk ranges from 1.5 to 2, compared with 10 for exposure to tobacco smoke, Dr. Zhang said.

About 50% of people lack the GSTM1 metabolic gene that can detoxify tobacco smoke and air pollution. Consequently, in these individuals, the potential of cancer development is increased by a relative risk of 1.5 to 2.0.

People who have this genetic defect and who have heavy exposure to pollution may have a higher risk of developing cancer, Dr. Zhang said, but a large sample size is needed to determine for certain whether this risk exists, he cautioned.

Once it is understood how genes and the environment work to contribute to cancer development, the knowledge can be applied to intervention. For example, individuals with genes that lead to a higher risk of cancer development may benefit from chemoprevention.

If air pollution is found to be a major contributor to cancer development, the medical community may need to encourage public policy to ensure clean air, he added.

Understanding who is at high risk can help reduce the expense of intervention, noted Dr. Zhang. For example, people with genetic defects who are more susceptible to tobacco smoke and who are regularly exposed to the carcinogen would benefit more from intervention than those without the genetic defects.

Breast Cancer

Progress in understanding the link between the environment and breast cancer is also being made. For example, the National Institute of Environmental Health Sciences (NIEHS) Sister Study will prospectively examine environmental and familial risk factors for breast cancer and other diseases in a cohort of 50,000 sisters of women who have had breast cancer.

“Breast cancer etiology is complex,” said Dale P. Sandler PhD, Acting Chief of the Epidemiology Branch, at the NIEHS. For example, genes can affect sporadic and familial cancer development.

Estrogen levels can also be important, but people process these hormones differently due to how estrogen receptors work and the various pathways of metabolism. Furthermore, genes may enhance exposure to one chemical, but decrease internal exposure to other chemicals.

Understanding the environmental link to cancer is a slowly emerging field, said Gwen W. Collman, PhD, Chief of the NIEHS Susceptibility and Population Health Branch in the Division of Extramural Research and Training.

The premise of the Sister Study is that participants have familial shared genes and shared environments, Dr. Sandler explained.

In the study population, sisters who are at an increased risk have on average a prevalence of genes and exposures that are greater than that of women selected randomly from the population. The gene-environment interaction is the key, she said.

“Genetic factors can regulate a girl's susceptibility to exposures in the environment,” Dr. Collman said, and genes can also affect the hormonal pathways that are key in breast cancer. Researchers need to look at genes related to the development of mammary glands and how the body handles environmental exposures.

Additionally, investigators continue to be interested in the impact of pesticides on breast cancer development. Bisphenol-A, a reproductive toxin that is found in plastic food containers and even baby bottles is also of interest in terms of the potential to affect breast cell growth or tumor risk. Chemical solvents used in computer chip production are also of concern.

Polyvinyl chloride (PVC), a compound used extensively in the manufacture of food packaging, medical products, appliances, toys, and other plastics may also play a role in breast cancer risk. Studies indicate that PVC can cause mammary gland tumors in animals but this has not been well studied in humans.

The Sister Study will also help investigators learn more about the effect of obesity, diet, and exercise on breast cancer development. Key risk factors of breast cancer such as the duration between onset of breast development and menarche will be considered.

Prostate Cancer

Environmental factors also play a role in prostate cancer—specifically, research indicates that animal fat in the diet has an impact on the disease, said Anil Kapoor, MD, Director of Urological Research and Surgical Director of Renal Transplantation at McMaster University.

For example, Japanese men tend to have a low incidence of the disease compared with North Americans, but Japanese men living in North America and eating a higher fat diet have the same incidence of prostate cancer.

Chemical carcinogens such as insecticides, asbestos, and lead also tend to increase prostate cancer risk, and smoking is also implicated.

Researchers at Fred Hutchinson Cancer Research Institute have found that middle-aged men who are long-term, heavy smokers face twice the risk of developing more aggressive forms of prostate cancer than men who have never smoked.

As with other cancers, genetics tends to interact with environmental factors to affect risk, Dr. Kapoor said. African American men and those with a family history of prostate cancer are more prone to the disease for genetic reasons.

Recent research (Prostate 2004 Nov 10, Epub ahead of print) indicates that specific genetic genotypes have an impact on risk. For example, CYP17/A1A1-A1A2 genotypes, GSTP1/IleVal genotype, PON192/QR, and PON55/LM-MM genotypes had a significantly higher risk of prostate cancer compared with the other genotypes.

Eating a high-fat diet and exposure to carcinogens only add to the genetic risk a man may have for developing prostate cancer, Dr. Kapoor said.

Men can take a number of steps to reduce their risk, including eating tomato-based foods that contain lycopenes, he said. Green leafy vegetables and low-fat, high-fiber diets also reduce risk. Avoiding smoking and exercising are other good strategies.

Additionally, researchers have found that taking aspirin, which is a COX inhibitor, as well as vitamins E and C and the mineral selenium may also reduce a man's chances of developing prostate cancer.

Dr. Kapoor also pointed to the importance of the Selenium and Vitamin E Cancer Prevention Trial (SELECT), which is randomizing 35,000 men.

Sister Study

The Sister Study, a long-term environmental and genetic study of women age 35 to 74 whose sisters had breast cancer, officially started enrollment a year ago, and the national launch was at the end of October. In the next three years, 50,000 women who live in the US and who have had at least one sister with breast cancer and do not have breast cancer themselves will be asked to join the study.

Further information is available at or by calling the toll-free number 1–877-4SISTER.

© 2005 Lippincott Williams & Wilkins, Inc.
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