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Biomarkers confirm higher incidence of thyroid cancer among respondents from the World Trade Center

Publicado em 05 agosto 2019

The incidence of thyroid cancer among first responders who worked voluntarily or as fire brigade, rescue and cleaning personnel at Ground Zero in New York on or after September 11, 2001 is three times higher than in the general population.

This difference has been confirmed by a method with a panel of four biomarkers that distinguish benign and malignant cases of thyroid cancer based on gene expression. The tests have been developed by researchers from the Federal University of São Paulo (UNIFESP) in Brazil in collaboration with colleagues at Johns Hopkins University School of Medicine in the United States. The study was supported by São Paulo Research Foundation – FAPESP as part of the thematic project.

The reasons for the increase in the incidence of thyroid cancer, revealed by previous research, are unclear. On 9/11 and for a long period thereafter, WTC respondents searched for survivors in the rubble and gave victims first aid after the deadliest foreign attack ever on American soil. Two hijacked passenger aircraft crashed into the World Trade Center (WTC) in Manhattan, causing the Twin Towers to collapse. A third plane crashed on the Pentagon in Washington DC. A fourth plane fell into a field in Pennsylvania after his passengers had thwarted the hijackers.

For years, it was believed that the higher incidence of thyroid cancer in this cohort could reflect overdiagnosis and large numbers of false-positive results in the screening program after 9/11. An article was recently published in the International Journal of Environmental Research and Public Health examines the results of a panel of four biomarkers used to analyze thyroid tumors in 37 responders controlled by the WTC Health Program and compares these individuals with non-WTC exposed individuals matched by age, gender and histology.

The researchers concluded that none of the WTC thyroid tumor assessments generated false positives and that all samples tested using the antibody-based cancer panel were malignant.

"To confirm cancer cases, we used a panel consisting of four biomarkers that could indicate whether a thyroid tumor was malignant or benign. This panel was developed by our team and was initially designed as a surgical test for thyroid nodules that are labeled without limit, because they could not be definitively classified as benign or malignant. The markers that we used are genes whose function in thyroid cancer is unknown and which is being investigated by our group, "said Janete Cerutti, professor of genetics at UNIFESP s School of Medicine, and principal investigator for the Thematic project.

The biomarkers were developed by the team at Cerutti's team between 2004 and 2011. These tests reflect the increased or decreased expression of genes associated with thyroid cancer.

After the seven-year development period, the group created a biomarker panel that is simpler than conventional tests because it is based on the expression of only four genes: DDIT3, ITM1, C1orf24 and PVALB.

The test distinguishes malignant tumors – follicular thyroid carcinoma, Hürthle cell carcinoma and papillary thyroid carcinoma – and benign lesions, such as follicular thyroid adenoma and Hürthle cell adenoma, by analyzing the combinations of gene expression markers.

"By piercing the tumors and analyzing the cells, we were able to observe the protein levels [produced by the expression of the four genes] present or absent in the cancer and thereby determine whether the tumors were malignant. The test will help doctors prescribe appropriate treatments, "Cerutti said.

The method is simpler and therefore cheaper than commercially available tests, she added. "It is a relatively simple test based on the combination of only four markers. Thyroid markers for thyroid cancer already exist, but they are much more complex than ours, with many more markers to detect possible genetic changes in tumors."

The cost of the new method is estimated to be less than a tenth of the diagnostic kits that are commercially available in Brazil, which can cost up to BRL 12,000 (now about USD 3,200) per use.

Avoid unnecessary surgery

The study confirming the increase in thyroid cancer among WTC respondents was based on data from participants in the Mount Sinai Hospital WTC Health Program, which monitors more than 27,000 respondents with annual examinations, laboratory tests and treatments for cancer, inflammatory diseases and mental illness.

"The program was worried about the high incidence of thyroid cancer, worried that this could be due to overdiagnosis or false-positive results, but we have shown that this is not the case. Annual screening and monitoring can really be thyroid cancer in an early detecting stage, increasing the chances of a favorable prognosis, "Cerutti said.

The study also confirmed the accuracy of the technique developed by Cerutti and its research group. "It was very important to get recognition from the WTC Health Program, to validate our method with a different population than the Brazilian group that we have been testing since 2011," she said.

According to the Brazilian National Cancer Institute (INCA), thyroid cancer is the fifth most common type of cancer in Brazilian women. The possibility of excessive numbers of false positives is also a concern in Brazil.

"High resolution ultrasonic imaging, capable of locating nodules as small as 2 mm, has significantly improved detection [cancerous and noncancerous] thyroid tumors, "Cerutti said.

Genetic analysis of the tumors would prevent unnecessary surgery, she noted. Thyroid nodules cannot be correctly classified in 30% of cases, because the characteristics of malignant cells are very similar to those of benign cells and the diagnosis requires surgical biopsy.

The study of WTC responders will be continued on two fronts, according to Cerutti. The dust and debris from the collapse of the towers will be examined for components that may have influenced the increase in thyroid cancer, and the team will also analyze the aggressiveness of these tumors.

"The analysis of tumor aggressiveness is being conducted here in our laboratory at UNIFESP. We wanted to identify the types of genetic changes that tumors show and identify the more aggressive ones. We analyze the mutations associated with poor prognosis at the molecular level." she said.

The team also studies the role of these molecular markers in the development of the disease. "We know that they play a role in its development. Our focus now is to discover why they raise or lower thyroid cancer. This knowledge will make an important contribution to prescribing a treatment, especially in cases where conventional treatment [surgery and radiation therapy] does not lead to healing, "Cerutti said.


About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution whose mission is to support scientific research in all areas of knowledge by awarding scholarships, scholarships and grants to researchers associated with higher education and research institutions in the state of São Paulo, Brazil. FAPESP is aware that the very best research can only be done through international collaboration with the best researchers. That is why it has set up partnerships with funding bodies, higher education, private companies and research organizations in other countries known for the quality of their research and has encouraged scientists who are funded by the grants to further develop their international cooperation. You can find more information about FAPESP at http: // /NL and visit FAPESP news agency at http: // /NL to keep abreast of the latest scientific breakthroughs, FAPESP helps with its many programs, prizes and research centers. You can also subscribe to FAPESP news agency at http: // /subscribe.