Higher incidence of leukemia in respondents on September 11

For the first time, a significantly higher incidence of leukemia was reported in those responding to the attacks that occurred on September 11, 2001 in New York City.

In a separate study, it was also discovered that these first responders had a higher rate of clonal hematopoiesis than similar controls, suggesting that their exposure to the dust cloud created when World Trade Center (WTC) towers collapsed may having increased the risk of myeloid cell mutations

In addition to leukemia, the overall incidence of all cancers was also high, particularly those of the thyroid and prostate, a new study reports.

The study was published today in JNCI Cancer Spectrum.

The researchers examined the incidence of cancer in almost 29,000 first responders, including police, 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 an increased risk of various types of cancer among people exposed to 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 rates (SIRs) for some types of hematologic malignancies, including myeloma, this is the first statistically significant elevated SIR for leukemia.

So why has leukemia reached the forefront only now, after almost two decades?

The study’s 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 the sample size was not large enough to detect a association. “But now time has passed, and there are more cases for analytical purposes, and we were able to find the association with more stable numbers,” he said.

“In addition, we do not detect leukemia per se,” Teitelbaum explained. Although he also pointed out that “responders have regular clinical blood tests, which may have detected leukemia.”

Another finding of the new study was that no dose-response association was observed between cancer risk and the estimated level of exposure. In other words, neither the time that respondents were exposed to toxins nor the intensity of exposure was related to the high incidence of cancer.

However, Teitelbaum noted that this is a limitation of the study because there is no way to measure exposure. “Everything informs itself, since the exposure was not being monitored,” he said. “We may have an inaccurate measurement of exposure and cannot predict any type of dose response based on the information we have.”

Several risk factors were identified that were related to an increased risk of developing cancer. These included the respondent’s age at the time of the attack, and also gender and smoking.

Gwen Nichols, MD, medical director of the Leukemia and Lymphoma Society, said the associations of old age and smoking are not surprising, “since we know that the risk of leukemia increases in smokers,” and acute myeloid leukemia , the most common. Adult leukemia and chronic lymphocytic leukemia are related to age.

It is also very unlikely that any exposure will be unifactorial when it comes to leukemia. “If someone is at greater risk, such as a smoker or being older, then exposure to environmental toxins may increase the risk more, compared to someone without those factors,” he said. “What we know about the causes of leukemia, from the point of view of exposure to toxins, is limited. It would be great to learn more, especially in this age of genetic testing, and to be able to tell people how to help reduce their risks “.

Increased incidence of cancer

The federally funded WTC Health Program was implemented to monitor and evaluate responders and provide treatment for conditions that were determined to be related to the September 11 attack. In this study, Teitelbaum and his colleagues evaluated the incidence of cancer in 28,729 members of the General Response Cohort, who enrolled from July 2002 to the end of 2013.

SIRs were calculated using two methods: inclusion of cancer cases and follow-up that began just after September 11, 2001 (without restrictions) and, to take into account selection bias, an observation that began 6 months after enrollment in the WTC Health Program (restricted).

The 28,729 respondents were predominantly men (85.5%), non-Hispanic whites (47.4%) and had an average age of 38 on September 11, 2001. The average time spent working in 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 increase in incidence (SIR, 1.09; 95% confidence interval [CI], 1.02-1.16). This elevation was mainly due to 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). In addition, the incidence of leukemia was also significantly high (SIR, 1.41; 95% CI, 1.01 – 1.92).

When observing other types of cancer, esophageal and brain cancers had a high incidence of 46% and 34%, respectively, but none were statistically significant. Lung cancer (SIR, 0.83; 95% CI, 0.66 to 1.03) and colorectal cancer (SIR, 0.81; 95% CI, 0.63 to 1.03) showed a decrease in incidence but, once again, none reached statistical significance.

In the unrestricted analysis, all cancer sites showed statistically significant increases in SIRs for cancer of all sites, and specifically for skin, prostate, bladder, kidney and thyroid cancer, hematologic malignancies, leukemia, non-Hodgkin lymphoma , multiple myeloma, and chronic lymphocytic leukemia.

Teitelbaum said it is difficult to predict what will be seen in the future in relation to the type of cancer and the incidence in respondents. “Some cancers have a very long latency and there is a large distribution of exposure to the actual identification of the disease,” he said. “Surveillance is ongoing and we encourage you to keep coming back. By monitoring your health, we have the ability to better understand cancers and other conditions related to WTC.”

Relationship with clonal hematopoiesis?

Speaking to Medscape Medical NewsNichols of the Leukemia and Lymphoma Society said that ongoing research can 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 myeloid cells related to an acquired genetic mutation, is a characteristic of myelodysplastic leukemia syndromes and leukemia. When it occurs in individuals without a hematological malignancy, it is known as clonal hematopoiesis of undetermined potential (CHIP).

CHIP is associated with an increased risk of a hematological malignancy, and a study recently presented at the annual meeting of the American Society of Hematology (ASH) found a higher rate of mutations in the WTC responders (11.9%) in comparison with an unexposed cohort (1.9%).

“We are supporting research that analyzes the development of CHIP over time, for multiple myeloma and leukemia,” said Nichols, who was not involved in any of the cancer association studies on September 11. “This study analyzed the development of CHIP in the first responders, and they saw an increase in clonal CHIP that was higher than one would expect, compared to controls of the same age.”

The researchers conducted a deep targeted sequencing of blood samples obtained from 481 first responders (429 firefighters exposed to the WTC, 52 emergency medical service workers exposed to the WTC) and 52 non-exposed first responders. The analysis was performed for 237 genes mutated in hematologic malignancies.

The findings reported in this summary suggest that exposure could be causing increases in mutational changes, he noted. “It has a fairly long latency and that may partly explain why we are seeing more leukemia now.”

The study is ongoing, and Nichols said he “hopes that an article will be published when the investigation 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 not revealed relevant financial relationships.

JNCI Cancer Spectr. Published on January 14, 2020. Full text

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