TERT and BRAF V600E mutations in thyroid cancer of World Trade Center Responders

Author:

van Gerwen Maaike12ORCID,Cerutti Janete Maria3,Mendes Thais Biude3,Brody Rachel4,Genden Eric1,Riggins Gregory J5,Taioli Emanuela267ORCID

Affiliation:

1. Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai , New York, NY 10029 , USA

2. Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029 , USA

3. Genetic Bases of Thyroid Tumor Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo , São Paulo, Pedro de Toledo 669, 11 Andar, São Paulo, 04039-032 SP , Brazil

4. Department of Pathology, Icahn School of Medicine at Mount Sinai , New York, NY 10029 , USA

5. Department of Neurosurgery, Johns Hopkins University School of Medicine , Baltimore, MD 21287 , USA

6. Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai , New York, NY 10029 , USA

7. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029 , USA

Abstract

Abstract The 2-fold excess thyroid cancer risk reported in multiple World Trade Center (WTC) disaster exposed cohorts cannot entirely be explained by surveillance and physician bias thus highlighting the need to investigate the potential consequences of the dust exposure, containing carcinogenic and endocrine disruptive elements, on the thyroid. This study investigated the presence of TERT promoter and BRAF V600E mutations in 20 WTC-exposed versus 23 matched non-exposed thyroid cancers as potential mechanism explaining the excess risk. Although no significant difference in BRAF V600E mutation was found, TERT promoter mutations were significantly more prevalent in WTC thyroid cancer versus non-exposed thyroid cancers (P = 0.021). The odds of a TERT promoter mutation was significantly higher in the WTC versus the non-WTC thyroid cancers after adjustment [ORadj: 7.11 (95% CI: 1.21–41.83)]. These results may indicate that exposure to the mixture of pollutants present in the WTC dust resulted in an excess thyroid cancer risk and potentially more aggressive thyroid cancer, warranting investigating WTC responders on thyroid-associated symptoms during their health checkups. Future studies should include long-term follow-up to provide important insights in whether thyroid-specific survival is negatively affected by WTC dust exposure and whether this is because of the presence of one or more driver mutations.

Funder

National Cancer Institute

National Institute for Occupational Safety and Health

Centers for Disease Control and Prevention

São Paulo Research Foundation

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,General Medicine

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