Higher incidence of leukemia found in 9/11 respondents

For the first time, a significantly higher incidence of leukemia has been reported in patients who responded to the attacks that occurred on September 11, 2001 in New York City.

In a separate study, these first responders also found a higher rate of clonal hematopoiesis than the corresponding controls, suggesting that their exposure to the dust cloud created by the collapse of the World Trade Center (WTC) towers may have increased the risk of myeloid cell mutations.

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

The study was published today in JNCI cancer spectrum.

The researchers looked at the incidence of cancer in nearly 29,000 first responders, including law enforcement, construction and telecommunications agents; 44.4% of this group had at least some level of exposure to the WTC dust cloud.

Previous studies have found a greater risk for different types of cancer among people exposed to WTC dust, which includes 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 hematological malignancies, including myeloma, this is the first statistically significant elevated SIR for leukemia.

So why did leukemia come to the fore only now, after almost two decades?

Study author Susan Teitelbaum, PhD, a professor of environmental medicine and public health at Mount Sinai’s Icahn School of Medicine in New York City, explained that previously the sample size was not large enough to detect an association. “But now the time has passed and there are more cases for analytical purposes and we have managed to find the association with more stable numbers,” he said.

“Also, we don’t control leukemia itself,” explained Teitelbaum. Although he also noted that “patients respond to regular clinical blood tests, which may have detected leukemia”.

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

However, Teitelbaum stressed that this is a limitation of the study because there is no way to measure exposure. “It’s all self-reported, since the exposure hasn’t been monitored,” he said. “It is possible that we have an inaccurate exposure measurement and we cannot predict any dose response from the information we have.”

Several risk factors have been identified that were related to a higher risk of developing cancer. These included the rescuer’s age at the time of the attack, as well as gender and smoking status.

Gwen Nichols, MD, Chief Medical Officer at the Leukemia & Lymphoma Society, observed that the associations of old age and smoking are not surprising, “as we know that the risk of leukemia 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 exposure is unactorial when it comes to leukemia. “If someone is at higher risk, such as a smoker or older, exposure to environmental toxins can increase the risk more than someone without those factors,” he said. “What we know about the causes of leukemia – from the point of view of toxin exposure – is limited. It would be nice to learn more, especially in this era of genetic testing, and to 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 evaluate rescuers and provide treatment for conditions determined to be related to the 9/11 attack. In this study, Teitelbaum and his colleagues evaluated the incidence of cancer in 28,729 members of the general response group, who were enrolled from July 2002 until the end of 2013.

SIRs were calculated by two methods: inclusion of the cancer case and follow-up started immediately after 11 September 2001 (without restrictions) and, in order to justify the distortion of the selection, the observation started 6 months after the enrollment in the WTC Health Program (limited).

The 28,729 patients who responded were predominantly male (85.5%), non-Hispanic whites (47.4%) and had an average age of 38 on 11 September 2001. The median time spent working on the rescue effort and recovery was 52 days.

A total of 1072 tumors were identified in 999 responders. In the limited analysis, all combined cancer sites showed a statistically significant increase in incidence (SIR, 1.09; 95% confidence interval [CI], 1.02 – 1.16). This elevation was mainly 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). In addition, the incidence of leukemia was also significantly high (SIR, 1.41; 95% CI, 1.01 – 1.92).

When other types of cancer were observed, esophageal and brain tumors had a high incidence of 46% and 34% respectively, but neither 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) they showed a decrease in the incidence but, again, they did not reach statistical meanings.

In the unrestricted analysis, all cancer sites showed statistically significant increases in SIRs for cancer at all sites and in particular for skin, prostate, bladder, kidney and thyroid cancers, hematological malignancies , leukemia, non-Hodgkin lymphoma, multiple myeloma, and chronic lymphatic leukemia.

Teitelbaum noted that it is difficult to predict what could be seen in the future in relation to the type of cancer and the incidence in the responding patients. “Some cancers have a very long latency and there is a huge distribution from exposure to actual identification of the disease,” he said. “Surveillance is ongoing and we encourage them to keep coming back. By monitoring their health, we have the ability to better understand cancers and other WTC-related conditions.”

Relationship with clonal hematopoiesis?

Speaking to Medscape medical newsNichols of the Leukemia & Lymphoma Society noted that ongoing research could also shed light on a “genetic link” between exposure and development of leukemia.

Clonal hematopoiesis (CH), a term used to describe a group of myeloid cells related to an acquired genetic mutation, is a feature of myelodysplastic syndromes and leukemias. When it occurs in individuals without hematological malignancy, it is known as clonal hematopoiesis of undetermined potential (CHIP).

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

“We are supporting research that is observing the development of CHIP over time for multiple myeloma and leukemia,” said Nichols, who was not involved in any 9/11 cancer association study. “This study looked at the development of CHIP in first responders and saw an increase in clonal CHIP that was greater than what would be expected compared to age-matched controls.”

The researchers conducted deep targeted sequencing in the blood samples obtained from 481 first responders (429 firefighters exposed to the WTC, 52 emergency medical workers exposed to the WTC) and 52 first responders not exposed. The analysis was performed for 237 mutated genes in hematological malignancies.

The results reported in this abstract suggest that exposure could cause increases in mutational changes, he noted. “It has a fairly long latency and this may partially explain why we are seeing more leukemia now.”

The study is ongoing and Nichols noted that “he hopes an article will be published once the research is complete.”

The study was supported by the Centers for Disease Control and Prevention / National Institute for Safety and Health at Work. The study authors and Nichols did not disclose relevant financial reports.

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

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