Link between environmental disasters, risk for cancer examined

A colossal earthquake and tsunami damaged Japan’s Fukushima Daiichi nuclear complex on March 11, leading to a meltdown and subsequent radiation exposure second only to the Chernobyl accident 25 years ago. These disasters bring to mind the nuclear attacks on Hiroshima and Nagasaki in 1945, and their subsequent contributions to disease and deaths attributed to radiation exposure.

This year also marks the 1-year anniversary of the BP oil spill in the Gulf of Mexico, an environmental hazard that has exposed area residents to a clear risk for increased cancers, but the amount of that excess risk remains in dispute.

The International Atomic Energy Agency (IAEA), WHO and the U.N. concluded in a report jointly published in 2005 that fewer than 50 people had died as a direct result of the Chernobyl meltdown. As quoted in a 2006 story in The Lancet, Burton Bennett, chairman of the Chernobyl Forum, the IAEA subcommittee that produced the report, said the reactor explosion was a “very serious accident with major health consequences.” Bennett’s group uncovered 4,000 cases of thyroid cancer they associated with Chernobyl, most in children; those cancers resulted in nine deaths. The committee did not find a sudden spike in other cancers or diseases.

Greenpeace called the findings “a gross underestimation,” and experts in the Ukrainian and Russian governments dismissed the report. Yelena Burlakova, chairwoman of the Council on Radiobiology of the Russian Academy of Sciences, called the IAEA a lobbying group for the nuclear industry, more concerned about protecting power plants than detailing negative health effects associated with radiation.

A 2008 report from the UN Scientific Committee on the Effects of Atomic Radiation found that more than 6,000 diagnoses of thyroid cancer in younger people were the direct result of exposure to radiation from Chernobyl, a fraction of the 93,000 cases Greenpeace said will eventually appear.

R. Michael Tuttle

“The Chernobyl accident was a tremendous disaster because of the huge amounts of radioactive iodine that spilled over northern Ukraine and Belarus. These areas were relatively iodine deficient, and very few people there received iodine prophylaxis. Within about 5 to 7 years, we saw an astronomic increase in the risk for thyroid cancer. Some raions [counties] that would have seen one or two cases of thyroid cancer per year were suddenly seeing up to 40 or 50 cases,” R. Michael Tuttle, MD, professor of medicine and attending physician of endocrinology service at Memorial Sloan-Kettering Cancer Center, said in an interview. Much of Tuttle’s research has focused on thyroid cancer after the Chernobyl accident, an area that he has visited more than 20 times.

In reality, the health impact of Chernobyl is a bit of a mystery, according to Kirsten B. Moysich, PhD, professor of oncology in the department of cancer prevention and control and academic program chair of the department of cancer pathology and prevention at Roswell Park Cancer Institute. More recent, better-designed studies suggest that the risk for other cancers was not as great as originally believed, but Moysich said the total number of excess cancers is unknowable.

“There were a lot of initial studies that didn’t employ the most rigorous epidemiological study designs, and initially those studies pointed to an increased risk for all types of cancers. The more rigorous epidemiologic studies, many of which were coordinated by the National Cancer Institute, didn’t really point to an excess risk except for thyroid cancer in children and adolescents,” she said in an interview.

Tuttle said “the huge fear was that there would be a tremendous rise in every cancer,” but that did not happen.

“We knew we were going to see rising rates of thyroid cancer, but we didn’t think it would happen so quickly because in other environmental/radiation accidents we didn’t start seeing an increase until after 10 or 15 years,” he said. “The difference is that the Chernobyl accident radiated millions of people and a lot of young children.”

Reports have also shown an age-related effect after Chernobyl.

“The [reports] appeared in a very young patient population compared with most thyroid cancers, which generally appear in an older population. … For thyroid cancers, there’s approximately a 400-fold increase,” Philip J. McCarthy Jr., MD, professor of oncology and director of the blood and marrow transplant program at Roswell Park, said in an interview.

Along with Per Hall, PhD, of Karolinska Institute in Stockholm, Moysich and McCarthy wrote an opinion published online April 26, in The Lancet that largely supported the work of the Chernobyl Forum.

“We concluded that, with the exception of thyroid cancer in young people, there was no strong evidence to suggest that excess cancer incidence was substantial in the aftermath of the accident,” they wrote.

In a review published online by The New England Journal of Medicine in April, Christodouleas and colleagues found that studies conducted among those exposed to radiation from Chernobyl did not show “consistently elevated risks” for leukemia and non-thyroid solid cancers.

There was strong evidence for a two- to fivefold per 1 Gy increased rate of secondary thyroid cancers among children who ingested iodine-131. The increase in relative risk is large, but Christodouleas and colleagues said the baseline incidence of thyroid cancer in children was just one case per 100,000 people.

In an interview, McCarthy and Moysich said that Soviet-era government secrecy kept the outside world from even learning about Chernobyl until days after the meltdown and inhibited efforts to study the immediate health effects. Additionally, there was little experience with long-term epidemiology at the time, and frustrating language barriers, cultural differences and the “daily challenges in covering a very large study area” made it extremely difficult to conduct research.

Looking back for answers

The nuclear attack on Hiroshima and Nagasaki may provide a better example of the potential health effects of Fukushima. The Japanese population has been studied rigorously and extensively in the decades since Fat Man and Little Boy laid waste to the two cities. Research into the health effects associated with Hiroshima and Nagasaki began with the Atomic Bomb Casualty Commission in 1947. The commission was reorganized in 1975 as the Radiation Effects Research Foundation.

The epidemiological Life Span Study began following 120,000 survivors and control subjects in 1955. The study included the Adult Health Study, a defined subset who would receive additional morbidity surveillance based on biennial health examinations. A third study was initiated to analyze people exposed to radiation in utero, and a fourth to examine a cohort of children conceived after the attack, both those exposed to radiation and their non-exposed counterparts, known as the F1 cohort. Overall, these ongoing studies include more than 200,000 people from the affected areas.

Evan Douple, PhD, is associate chief of research for the Radiation Effects Research Foundation and helped author an article published earlier this year in Disaster Medicine and Public Health Preparedness that looked at risk estimates for radiation-related health effects associated with the bombings. Douple, a professor of medicine at Dartmouth Medical School for 20 years and former director of the biomedical engineering program of the Norris Cotton Cancer Center, said survival 66 years later has been better than researchers expected.

“Most scientists expected higher rates of cancer and some evidence for radiation-induced mutations in the F1 generation,” Douple said. “However, an overall excess of around 10% is relatively small, and there is still no evidence of increased health effects in the F1. The longevity of the Japanese life span is also amazing until you consider that Japan is one of the longest-living countries in the world.”

Roughly 40% of those who survived the attack are still alive, according to results of the study by Douple and researchers. However, survival is approximately 80% for those exposed before age 20 years. Researchers said the incidence of cancer will rise in the coming years because people who were aged younger than 20 years at exposure are becoming elderly and more susceptible to disease.

Fewer than 1,000 solid cancers can be attributed to the bombings. Of 17,448 solid cancer diagnoses in a subcohort of more than 100,000 patients in the Life Span Study, 853 are thought to be the result of radiation exposure. That represents 11% of all of the solid cancers among survivors exposed to 0.005 Gy. The proportion of cancers attributable to the bombs increases to 48% among those who were exposed to at least 1 Gy.

Researchers found the highest excess RR (0.8 or 80%/Gy) for bladder, female breast and lung cancers. Excess RR was also relatively high (0.5-0.8 or 50%-80%/Gy) for cancers of the thyroid, brain/central nervous system, ovary, colon and esophagus. A different ranking is obtained when one examines excess absolute risks, which have clinical or public health implications. Excess RR for female breast cancer is among the highest in solid cancers, at 0.87.

Female breast, thyroid, stomach, colon, lung, liver and bladder cancers have the highest excess absolute risk, which reflects higher numbers of excess cancers. For stomach and liver cancers, the excess RR of 0.3 is modestly high, but the excess in absolute risks is extremely high because of the high baseline rates for these cancers in Japan.

Researchers did not find a significant association with radiation exposure for rectal cancer, prostate cancer and malignant melanoma.

Unfortunately, whatever insights that can be gleaned from Hiroshima and Nagasaki must be tempered by the reality that Fukushima is a very different event. The two bombs produced an intense, relatively brief exposure to radiation, whereas exposure from Fukushima will be low-level and long-lasting. Tuttle said many people think that every radiation is the same; however, that is not the case. There are two different types of radiation-induced cancer: cancer caused by external beam radiation and cancer caused by fallout.

“The risk estimates from Hiroshima and Nagasaki represent a worst-case scenario and therefore are very useful as a worst-case scenario for radiation protective standards and for estimating potential health effects,” Douple said.

He added that Japan will likely experience a slight increase in cancer risk over time.

“It would be expected that one would probably not be able to measure a statistically significant excess,” he said. “However, it will depend on the dose information received for the early accident time periods.”

The long-term threat of oil

On the other side of the world, the Gulf oil spill is less likely to present short-term cancer risks like the nuclear events. While the nuclear events show a strong increase in thyroid cancer incidence, and especially among those who were younger at exposure, the risk from the oil spill comes from benzene and polycyclicaromatic hydrocarbons (PAH).

Benzene, found in concentrations of 1% to 6% in crude oil, is a known hematotoxicant and hematocarcinogen. Exposure in this case should be limited because the benzene evaporated before reaching shore, but workers at sea and close to the spill, such as the hundreds of local fishermen hired to work on the cleanup, could be at greater risk for the acute adverse health effects of benzene, depending on the duration of their exposure. Long-term exposure to benzene has also been associated with leukemia.

PAH may represent the greater risk for cancer incidence because it is more persistent and can bio-accumulate. PAH is associated with skin and lung cancers, as well as reproductive and developmental toxic effects. A review published in the April 7, issue of The New England Journal of Medicine concluded that although the oil spill workers were likely to experience acute effects due to exposure to PAH and other volatile organic components of crude oil, such as simple aromatics and shorter aliphatic straight-chain hydrocarbons, but that the toxic compounds were probably not present in concentrations great enough to cause long-term health effects.

As many as 52,000 people participated in the cleanup in some capacity, according to the National Institute for Occupational Safety and Health.

Maureen Lichtveld

Whatever the risks associated with the spill may be, they probably will not appear for years if not decades. Maureen Lichtveld, MD, MPH, Freeport McMoran chair of environmental policy in the department of environmental health sciences at the Tulane University School of Public Health & Tropical Medicine, said that means it will be extremely difficult to quantify the number of directly associated cancers.

“Establishing a definite relationship between exposure to environmental contamination and cancer can be very difficult. The few instances we have — asbestos and mesothelioma; benzene and leukemia; PAHs and other cancers; radiological agents and thyroid cancer — are really the exception rather than the rule,” she said. “In most cases, the exposures are a mixture [of elements], making it even harder to discern a definitive association, or a cause-and-effect linkage between environmental exposures and cancers. The work that we have to do begins in the laboratory, but very much ends within our communities.”

That said, Mississippi, Alabama and Louisiana, the states affected by the spill, rank among the worst for a variety of heath indicators, including diabetes, hypertension and cancer mortality associated with breast and prostate cancer, according to The New England Journal of Medicine. Louisiana is home to the infamous “Cancer Alley,” an 85-mile stretch along the Mississippi River between New Orleans and Baton Rouge that is home to several oil refineries and chemical plants, known for a high number of cancer diagnoses and cancer deaths.

Considering the current state of health in Louisiana, Lichtveld, who spent 18 years with the CDC in various capacities, including medical officer and senior medical toxicologist, said the oil spill could make the problem worse in an already vulnerable population.

“There have been concerns about cancer clusters in this area, but it is difficult to definitively show that indeed there is an elevated rate of cancer, and therefore, there’s a potential for a double whammy,” said Lichtveld, who is also associate director, Populations Sciences of the Louisiana Cancer Research Consortium. “However, that doesn’t excuse us from being very vigilant in this population and being aware of the historic burden of health disparities.”

Fears likely outstrip the risks

Estimates of health risks after the Fukushima accident are varying.

“We have already begun seeing reports in which people are saying that the accident in Fukushima may be just as bad as Chernobyl,” Tuttle said. “But, with regard to thyroid cancer, the Fukushima experience is probably going to be different.”

John D. Boice Jr., ScD, a radiation epidemiologist and professor in the department of medicine at Vanderbilt University, discussed the possible health implications of radiation from the Fukushima Daiichi nuclear power plant accident before the House Committee on Science, Space and Technology’s Energy & Environment and Investigations & Oversight Committees Hearing on Nuclear Energy Risk Management on May 13.

In his testimony, Boice said that “Fukushima is not Chernobyl,” and “the health consequences for Japanese workers and the public appear to be minor.

“While Fukushima is clearly a major reactor accident, the potential health consequences associated with radiation exposures in terms of loss of life and future cancer risk are small, particularly in contrast with those resulting from the Chernobyl accident some 25 years ago,” Boice said before the committee. Radiation releases are estimated to be up to 10% of that from Chernobyl, according to Boice, who is also scientific director of the International Epidemiology Institute. He has spent his career studying human populations exposed to radiation.

Boice’s estimates were “borne out in one survey of over 1,000 children who had their thyroids measured for possible uptakes of radioactive iodine [after Fukushima]. Not one child had a measurement above detectable limits.”

“Not only was there lower-dose radiation after the Fukushima accident, but a lot of the radiation blew out over the ocean, as opposed to Chernobyl where the radiation covered populated areas,” Tuttle said.

Similar to Boice, Tuttle also attributed lower health risk estimates to the Japanese authorities’ quick response. The approximately 200,000 inhabitants living near the damaged reactors were evacuated quickly; food and water were monitored for contamination; foods with increased radiation levels were banned; and stable iodine pills and syrup were distributed.

Disaster preparedness

With these past and recent events in mind, the American Thyroid Association released a call to action in May addressing preparedness around nuclear facilities in the US, stating that “advance preparations are needed” for nuclear accidents.

The expert association urged health care professionals and the public to contact appropriate representatives in Congress to support making potassium iodide available free to state and local governments for distribution to residents living within 20 miles of a nuclear power plant. According to the ATA, programs to make potassium iodide available are currently approved, but have not been implemented. Since 1984, the ATA has advocated that potassium iodide be part of an emergency plan that includes evacuation, sheltering and avoiding contaminated food, milk and water. The association suggests that it should be made available to people living within 200 miles of a nuclear power plant and should be predistributed to households within 50 miles of a plant.

US Rep. Edward Markey, D-Mass., sent a letter urging President Obama to implement the 2002 law to protect Americans in at least 33 states against the possibility of a radioactive iodine release from a nearby nuclear reactor. Section 127 of the Bioterrorism Preparedness and Response Act of 2002 directed the president to establish a program to make potassium iodide available free to state and local governments for distribution to residents living within 20 miles of a nuclear power plant.

“To our great disapproval, this legislation has not been put into action,” the statement reads. “The prevailing practice today continues to be potassium iodide distribution limited to just those within 10 miles of a nuclear power plant, and only in states that request it from the Nuclear Regulatory Commission.” – by Jason Harris and Katie Kalvaitis

For more information:

• Christiani DC. N Engl J Med. 2011;364:791-793.
• Christodouleas JP. N Engl J Med. 2011;doi:10.1056/NEJMra1103676.
• Douple EB. Disaster Med Public Health Preparedness. 2011;5:S122-S133.
• Goldstein BD. N Engl J Med. 2011;364:1334-1348.
• Lancet Oncol. 2011;12:409.
• Lyons RA. J. Epidemiol Community Health. 1999;53:306-310.
• Moysich KB. Lancet. 2002;3:269-279.
• Moysich KB. Lancet. 2011;12:416-418.
• Nauman J. Am J Med. 1993;94:524-532.
• Parfitt T. Lancet. 2006;367:1305-1306.
• Tyson FL. Cancer. 1998;83:1784-1792.

Disclosure: None of the sources in this article reported any relevant financial disclosures.

Who should receive iodine prophylaxis in the event of a nuclear emergency in the US?

Children, pregnant and lactating women and younger adults

Elizabeth N. Pearce

Evidence strongly favors potassium iodide use in children and in pregnant and lactating women following nuclear accidents. Most data on the risk for thyroid cancer comes from the Chernobyl accident, which, unfortunately, supplied the widest experience with exposure of children to radioactive iodine. There was an increase in thyroid cancer incidence among individuals who were children or who were in utero and had exposure at the time of the Chernobyl accident. Studies have suggested that, if taken rapidly enough following exposure, potassium iodide will block uptake of radioactive iodine into the thyroid so it can protect the thyroid against the harmful effects of radiation. In children who are likely to be at risk, as we know from the Chernobyl accident, this absolutely makes sense. In women who are breast-feeding, we know that radioactive iodine is secreted into breast milk, so a breast-fed baby would be at risk if the mother was not protected.

The most widespread use of potassium iodide following a nuclear accident occurred in Poland, where, after the Chernobyl accident, 18 million people were dosed. This experience demonstrated that widespread potassium iodide prophylaxis is safe. In Poland, there were only a handful of serious adverse events related to potassium iodide ingestion.

Between age 20 years and 40 years, I do not think there is a firm cut-off for who is at risk. Many factors are probably involved, including underlying dietary iodine status and levels of radioactive iodine exposure. Without hard and fast cut-offs for where exactly the threshold should be, age 40 years seems rational, given that we think it is a pretty low-risk intervention in adults up to that age. Risk for thyroid cancer following radioactive iodine exposure is low in older adults. I do not think there is a good rationale for potassium iodide prophylaxis in non-pregnant and non-lactating individuals older than the age of 40 years.

Elizabeth N. Pearce, MD, MSc, is associate professor of medicine at Boston University School of Medicine.

Disclosure: Dr. Pearce reports no relevant financial disclosures.

Everyone

Kenneth D. Burman

Although children have a higher risk for radiation-induced thyroid nodules and thyroid cancer, the risk is not limited only to children. While I agree that prophylaxis is vital in younger populations, it is also important to consider the risks and benefits for all age groups.

Data from the Poland experience, in which the population received iodine prophylaxis following the Chernobyl accident, show that it prevented thyroid cancer, as best as an epidemiologic study can show, in all age groups analyzed, not just in children. In Poland, they did not note a higher risk for thyroid nodules and thyroid cancer, as opposed to the surrounding countries.

The major reasons to limit prophylaxis to certain groups (eg, children, young adults) would relate to expense, logistics and the potential for adverse events from the radioactive iodine exposure. The risks to the thyroid gland are increased in the younger population, but are also increased, to a lesser extent, in adults. It obviously presents more administrative and logistical issues to offer iodine prophylaxis to both children and adults as compared with children alone. When giving excess iodine, people with underlying thyroid disorders such as Hashimoto’s thyroiditis, for example, may become hypothyroid or hyperthyroid. The risk is higher in older people because they have higher rates of underlying thyroid abnormalities. It does appear that multiple factors, such as endemic iodine sufficiency or deficiency, can influence the rates of thyroid cancer in radiation-exposed populations. However, it seems most prudent to follow the ATA’s recommendations and provide iodine prophylaxis for children and adults of any age, with the caveat, of course, that older individuals will have less of an opportunity and likelihood of developing thyroid cancer over time.

The issue as to what populations should receive iodine prophylaxis is controversial. Further detailed analysis of costs, benefits and risks of the approach presented is required, as well as assessment of the effectiveness of various doses of iodine prophylaxis in younger and older individuals to prevent radiation exposure.

Kenneth D. Burman, MD, is chief of the endocrine section at Washington Hospital Center and is professor in the department of medicine at Georgetown University.

Disclosure: Dr. Burman reports no relevant financial disclosures.