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9/11 firefighters face increased blood cancer risk

NYfirefightersA study reports that New York City firefighters exposed to the 9/11 World Trade Centre disaster site face an increased risk for developing myeloma precursor disease (MGUS), which can lead to the blood cancer multiple myeloma. The study was conducted by researchers at Albert Einstein College of Medicine, Montefiore Health System, the Fire Department of the City of New York (FDNY) and Memorial Sloan Kettering Cancer Centre.

"With our 2011 study, we were the first to show that first responders were more likely to get many different types of cancer," said senior co-author Dr David J Prezant, a professor of medicine at Einstein, a pulmonary disease specialist at Montefiore and chief medical officer of the FDNY. "We carried out this new study to do more than just treat cancer. We wanted to find early, predictive signs of cancer that would allow us to screen people and monitor those found to be at risk. By detecting MGUS, which predicts the development of multiple myeloma, we are able to do that."

In MGUS (monoclonal gammopathy of undetermined significance), the blood's plasma cells produce an abnormal protein called monoclonal (M) protein that can be detected with blood tests. MGUS generally causes no problems but can progress to multiple myeloma, a blood cancer diagnosed in about 30,000 Americans each year. In multiple myeloma, rapidly proliferating plasma cells can crowd out the bone marrow's normal blood-forming cells, leading to problems including anaemia (shortage of red cells) and leukopenia (shortage of white cells). Most multiple myeloma cases are diagnosed in people older than 65, and only 5% of cases occur among people under 50. Half of those diagnosed with multiple myeloma are still alive five years later.

Previous studies suggest that MGUS and multiple myeloma all tend to develop after exposure to toxic chemicals. The aerosolised dust from the collapsed towers exposed FDNY and other first responders to unprecedented levels of polychlorinated biphenyls, polycyclic aromatic hydrocarbons, dioxins, asbestos and other potential carcinogens, as well as diesel smoke from heavy machinery used in the 10-month rescue and recovery effort.

For statistical reasons, the study population was limited to 781 white, male WTC-exposed firefighters aged 50 to 79 whose blood samples were evaluated to assess the prevalence of MGUS in the group. When results were compared with MGUS prevalence in a non-exposed comparison group (men living in Olmsted County, MN), the prevalence of MGUS in the firefighters was nearly twice as high (7.63 cases of MGUS per 100 firefighters vs 4.34 cases per 100 non-exposed persons).

"We saw a significantly higher incidence of MGUS in these first responders, and they're developing it at a young age," said the study's senior co-author Amit Verma, a professor of medicine and of developmental & molecular biology at Einstein and director of hematologic malignancies at the Montefiore Einstein Centre for Cancer Care. Their early development of MGUS, he says, suggests that these firefighters potentially face an increased risk for early-onset of multiple myeloma as well.

Indeed, in a separate analysis, the researchers examined the 16 cases of multiple myeloma diagnosed between 12 September, 2001 and 1 July, 2017 among all white, male WTC-exposed FDNY firefighters. Their average age of diagnosis was 57, or 12 years younger than the average age for multiple myeloma diagnosis nationally.

Although not everyone with MGUS will develop multiple myeloma, the researchers recommend that physicians screen first responders exposed to the WTC site for both conditions. "Screening for multiple myeloma risk by testing for MGUS is something we can offer these first responders, which is why this study is important," said Prezant.

Importance: The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood.
Objective: To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS.
Design, Setting, and Participants: Case series of multiple myeloma in firefighters diagnosed between September 11, 2001, and July 1, 2017, together with a seroprevalence study of MGUS in serum samples collected from Fire Department of the City of New York (FDNY) firefighters between December 2013 and October 2015. Participants included all WTC-exposed FDNY white, male firefighters with a confirmed physician diagnosis of multiple myeloma (n = 16) and WTC-exposed FDNY white male firefighters older than 50 years with available serum samples (n = 781).
Exposures: WTC exposure defined as rescue and/or recovery work at the WTC site between September 11, 2001, and July 25, 2002.
Main Outcomes and Measures: Multiple myeloma case information, and age-adjusted and age-specific prevalence rates for overall MGUS (ie, MGUS and light-chain MGUS), MGUS, and light-chain MGUS.
Results: Sixteen WTC-exposed white male firefighters received a diagnosis of multiple myeloma after September 11, 2001; median age at diagnosis was 57 years (interquartile range, 50-68 years). Serum/urine monoclonal protein isotype/free light-chain data were available for 14 cases; 7 (50%) had light-chain multiple myeloma. In a subset of 7 patients, myeloma cells were assessed for CD20 expression; 5 (71%) were CD20 positive. In the screening study, we assayed peripheral blood from 781 WTC-exposed firefighters. The age-standardized prevalence rate of MGUS and light-chain MGUS combined was 7.63 per 100 persons (95% CI, 5.45-9.81), 1.8-fold higher than rates from the Olmsted County, Minnesota, white male reference population (relative rate, 1.76; 95% CI, 1.34-2.29). The age-standardized prevalence rate of light-chain MGUS was more than 3-fold higher than in the same reference population (relative rate, 3.13; 95% CI, 1.99-4.93).
Conclusions and Relevance: Environmental exposure to the WTC disaster site is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype.

Ola Landgren, Rachel Zeig-Owens, Orsolya Giricz, David Goldfarb, Kaznouri Murata, Katie Thoren, Lakshmi Ramanathan, Malin Hultcrantz, Ahmet Dogan, George Nwankwo, Ulrich Steidl, Kith Pradhan, Charles B Hall, Hillel W Cohen, Nadia Jaber, Theresa Schwartz, Laura Crowley, Michael Crane, Shani Irby, Mayris P Webber, Amit Verma, David J Prezant

[link url=""]Alfred Einstein College of Medicine material[/link]
[link url=""]JAMA Oncology abstract[/link]
[link url=""]JAMA Oncology editorial[/link]

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