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July 27, 2022
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Sept. 11 responders with low IgE at greater risk for blood cancers

Fact checked byKristen Dowd
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Firefighters and EMS providers with low levels of serum IgE who responded to the attack on the World Trade Center on and after Sept. 11, 2001, had significantly higher odds for developing a hematologic malignancy, a recent study reported.

However, the odds for developing solid tumors were similar among firefighters regardless of their IgE level, Denisa E. Ferastraoaru, MD, attending physician and associate professor of medicine in allergy and immunology at Albert Einstein College of Medicine in New York City, and colleagues wrote in the study, published in Annals of Allergy, Asthma & Immunology.

Proportions of first responders after 9/11 who developed hematologic malignancies included 7.3% of responders with low IgE and 1.5% of responders with normal through very high IgE.
Data were derived from Ferastraoaru D, et al. Ann Allergy Asthma Immunol. 2022;doi:10.1016/j.anai.2022.07.012.

“Previous work showed that World Trade Center (WTC) responders have higher incidence of cancer, possibly because of exposure to elevated carcinogen levels. Since the majority of WTC-exposed responders did not develop a malignancy, we were interested in exploring if differences in biological processes with a role in anti-tumor surveillance might play a role in malignancy development in conjunction with these environmental exposures,” Ferastraoaru told Healio.

Denisa E. Ferastraoaru

 

“It has been shown that patients with absent or very low IgE levels have higher risk of developing a malignancy. Therefore, we sought to investigate the association between IgE levels and risk of malignancy in WTC responders from the Fire Department of the City of New York,” she continued. 

The study involved 11,469 firefighters and EMS providers with no prior diagnosis of cancer who had worked at the World Trade Center site between Sept. 11, 2001, and July 24, 2002.

Researchers measured total serum IgE levels among 1,851 responders (median age, 41.7 years; 98.2% men; 88.7% white; 90.2% firefighters), including 709 responders within the 6 months after the attack and 1,142 responders more than 6 months later.

The other 9,633 responders (median age, 39.9 years; 96.8% men; 86.9% white; 85.1% firefighters) did not have their IgE measured.

A similar proportion of the groups who did vs. did not have their IgE measured developed a hematologic cancer (2% vs. 1.6%) or solid tumor (11.9% vs. 11%), with similar times to diagnosis following Sept. 11 (12.1 years; interquartile range [IQR], 7.3-15.9 vs. 11.6 years; IQR, 7.7-15.6).

Fifty-five responders were classified as having low IgE — defined as less than 36.58 kU/L — with a median IgE level of 25.95 kU/L (range, 4-36.47). The 1,796 responders who did not have low IgE had a median level of 188.62 (range, 36.58-9,021.13). None of the responders had IgE deficiency, defined as less than 2.5 kU/L.

Four (7.3%) of the responders in the low IgE group developed hematologic malignancies including leukemia (n = 1), multiple myeloma (n = 1) and lymphoma (n = 2), compared with 26 (1.5%) of the responders with higher IgE levels (P < .01).

After adjusting for confounders, responders with low IgE levels had a 7.81 times (95% CI, 1.77-29.35) greater risk for developing a hematologic cancer than responders with higher levels.

Responders with low IgE faced a greater risk for hematologic cancers compared with all other groups of IgE levels, but the difference only maintained significance when evaluating those with high IgE levels, or levels between 100 kU/L to less than 1,000 kU/L (OR = 12.96; 95% CI, 2.47-56.12).

The rate of solid tumors did not significantly differ between those with low and non-low IgE levels (5.5% vs. 11.4%).

An analysis of the responders whose IgE levels were measured within 6 months of the attack showed similar results, with two of 30 (6.7%) responders with low IgE levels and eight of 679 (1.2%) responders with higher levels reporting hematologic malignancies (P < .01; OR = 7.66; 95% CI, 0.59-41.04). The rate of solid tumors between the two groups appeared similar (3.3% vs. 10.2%).

“We found that the WTC responders with IgE measurements in the lowest third percentile had a significantly higher proportion and odds of developing a hematologic malignancy after the 9/11 attacks, compared with responders with non-low IgE levels,” Ferastraoaru said.

 

“This is the first study to show that, being exposed to carcinogens, among WTC-exposed rescue/recovery workers, a low serum IgE level is associated with malignancy development,” she said.

Noting these greater odds for hematologic malignancies among responders with low IgE levels, the researchers said that identifying such individuals could be important for further clinical follow-up and management.

“The results of this pilot study raise the possibility that individuals with low IgE levels have increased odds for developing cancer under certain conditions, such as exposure to carcinogens,” Ferastraoaru said. “If so, identifying such individuals may be important for further clinical cancer screening. This would improve the chance for detecting cancers early so that treatment can be initiated.” 

The median age of diagnosis of these malignancies was the early 50s in the group with low IgE, although the national median age for developing leukemia, lymphoma or multiple myeloma is between 67 and 69 years.

“At this time, there is no biomarker reflecting deficient antitumor immunity that could be utilized in clinical practice to predict malignancy susceptibility. The data so far suggest that in certain conditions, very low IgE levels might emerge as a potential biomarker for cancer susceptibility,” Ferastraoaru said.

“Although the exact IgE threshold which poses a higher risk for cancer occurrence has yet to be established, its utility as a screening instrument might have broad implications as a useful tool to predict cancer predisposition,” she continued. 

The researchers recommended larger, multicenter studies with adequate follow-up of patients with different IgE levels to assist in these efforts.

“This is a pilot study, and more work needs to be done to confirm these promising findings,” Ferastraoaru said.

“We are planning to expand this pilot study and measure IgE levels in the remaining stored samples from the FDNY WTC responders in order to better assess the relationship between malignancy occurrence and IgE levels, as well as the proper follow up and management of these individuals,” she said.