For the first time, a significantly higher incidence of leukemia has been reported in responders to the attacks that occurred on September 11, 2001, in New York City.
In a separate study, these first responders were also found to have a higher rate of clonal hematopoiesis than matched controls, suggesting that their exposure to the dust cloud created when the World Trade Center (WTC) towers collapsed may have increased the risk of mutations in myeloid cells.
In addition to leukemia, the overall incidence of all cancers was also elevated, particularly those of the thyroid and prostate, a new study reports.
The study was published today in JNCI Cancer Spectrum.
Researchers examined cancer incidence in almost 29,000 first responders, including law enforcement, construction, and telecommunications workers; 44.4% of this group had at least some level of exposure to the WTC dust cloud.
Previous studies have found a higher risk for several cancer types among persons exposed to the WTC dust, which comprises a complex mixture of asbestos, silica, benzene, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, volatile organic compounds, and metals. Although previous research has shown higher standardized incidence ratios (SIRs) for some types of hematologic malignancies, including myeloma, this is the first reported statistically significant elevated SIR for leukemia.
So why has leukemia come to the forefront only now, after almost two decades?
Study author Susan Teitelbaum, PhD, professor of environmental medicine and public health at the Icahn School of Medicine at Mount Sinai in New York City, explained that previously the sample size wasn't large enough to detect an association. "But now time has gone on, and there are more cases for analytic purposes, and we were able to find the association with more stable numbers," she said.
"Additionally, we do not screen for leukemia per se," Teitelbaum explained. Although she also noted that "the responders do get regular clinical blood tests, which may have picked up the leukemia."
Another finding from the new study was that no dose-response association was observed between cancer risk and estimated level of exposure. In other words, neither the length of time that responders were exposed to toxins nor the intensity of the exposure was related to the elevated incidence of cancer.
However, Teitelbaum pointed out that this is a limitation of the study because there isn't any way to measure exposure. "It is all self-reported, as exposure wasn't being monitored," she said. "It is possible that we have an imprecise measurement of exposure and we are not able to predict any type of dose response from the information we have."
Several risk factors were identified that were linked to a higher risk of developing cancer. These included the age of the responder at the time of the attack, and also gender and smoking status.
Gwen Nichols, MD, chief medical officer at the Leukemia & Lymphoma Society, noted that the associations of older age and smoking are not surprising, "as we know that leukemia risk is increased in smokers," and both acute myeloid leukemia — the most common leukemia in adults — and chronic lymphocytic leukemia are both age related.
It is also highly unlikely that any one exposure is unifactorial when it comes to leukemia. "If someone is at higher risk, such as a smoker or being older, then exposure to environmental toxins may increase the risk more, as opposed to someone without those factors," she said. "What we know about causes of leukemia — from the standpoint of exposure to toxins — is limited. It would be great to learn more, especially in this era of genetic testing, and be able to tell people how to help reduce their risks."
Cancer Incidence Increased
The federally funded WTC Health Program was implemented to monitor and assess responders and provide treatment for conditions determined to be related to the 9/11 attack. In this study, Teitelbaum and her colleagues evaluated cancer incidence in 28,729 members of the General Responder Cohort, who were enrolled from July 2002 until the end of 2013.
SIRs were calculated with two methods: cancer case inclusion and follow-up that began right after September 11, 2001 (unrestricted) and, in order to account for selection bias, observation that began 6 months after enrollment in the WTC Health Program (restricted).
The 28,729 responders were predominantly male (85.5%), white non-Hispanic (47.4%) and had a median age of 38 on September 11, 2001. The median time spent working on the rescue and recovery effort was 52 days.
A total of 1072 cancers were identified in 999 responders. In the restricted analysis, all cancer sites combined showed a statistically significant elevation in incidence (SIR, 1.09; 95% confidence interval [CI], 1.02 - 1.16). This elevation was primarily driven by the high incidence of prostate cancer (SIR, 1.25; 95% CI, 1.11 - 1.40) and thyroid cancer (SIR, 2.19; 95% CI, 1.71 - 2.75). Additionally, the incidence of leukemia was also significantly elevated (SIR, 1.41; 95% CI, 1.01 - 1.92).
When looking at other cancer types, esophageal and brain cancers had an elevated incidence of 46% and 34%, respectively, but neither one was statistically significant. Lung cancer (SIR, 0.83; 95% CI, 0.66 - 1.03) and colorectal cancer (SIR, 0.81; 95% CI, 0.63 - 1.03) showed a decrease in incidence but, again, neither achieved statistical significance.
In the unrestricted analysis, all cancer sites showed statistically significant increases in SIRs for all-sites cancer, and specifically for melanoma of the skin, prostate, bladder, kidney and thyroid cancers, hematologic neoplasms, leukemia, non-Hodgkin lymphoma, multiple myeloma, and chronic lymphocytic leukemia.
Teitelbaum noted that it is difficult to predict what may be seen in the future in relation to cancer type and incidence in responders. "Some cancers have a very long latency and there is a huge distribution from exposure to the actual identification of disease," she said. "Surveillance is continuous, and we encourage them to keep coming back. By monitoring their health, we have the ability to gain a better understanding of cancers and other WTC related conditions."
Relationship to Clonal Hematopoiesis?
Speaking to Medscape Medical News, Nichols, of the Leukemia & Lymphoma Society, noted that ongoing research may also shed some light on a "genetic link" between exposure and the development of leukemia.
Clonal hematopoiesis (CH), a term used to describe a group of related myeloid cells with an acquired gene mutation, is a characteristic of myelodysplastic syndromes and leukemias. When it occurs in individuals without a hematologic malignancy, it is known as clonal hematopoiesis of indeterminate potential (CHIP).
CHIP is associated with an increased risk for a hematologic malignancy, and a study presented recently at the annual meeting of the American Society of Hematology (ASH) found a higher rate of mutations in WTC responders (11.9%) as compared with a non-exposed cohort (1.9%).
"We are supporting research that is looking at the development of CHIP over time, for multiple myeloma and leukemia," said Nichols, who was not involved with either 9/11 cancer association study. "This study looked at the development of CHIP in first responders, and they saw an increase in clonal CHIP that was higher than what one would expect, as compared to age matched controls."
The researchers conducted deep targeted sequencing in blood samples obtained from 481 first responders (429 WTC-exposed firefighters, 52 WTC-exposed emergency medical service workers) and 52 non-exposed first responders. Analysis was done for 237 genes mutated in hematologic malignancies.
The findings reported in this abstract suggest that exposure could be causing increases in mutational changes, she noted. "It has a fairly long latency and that may partially explain why we're seeing more leukemia now."
The study is ongoing, and Nichols noted that she is "hopeful that a paper will published when the research is completed."
The study was supported by the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The study authors and Nichols have disclosed no relevant financial relationships.
JNCI Cancer Spectr. Published January 14, 2020. Full text
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