# Thyroid Cancer Aggressiveness in WTC Responders

> **NIH ALLCDC U01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $999,987

## Abstract

Project summary
There is an increased incidence of thyroid cancer reported in World Trade Center (WTC) first
responders. We found no evidence from our previous research that these are false-positives
because of enhanced surveillance of the WTC cohort; it remains unclear why there is this
excess risk and in which ways exposure to Ground Zero may be contributing to thyroid
malignancy. Moreover, as of yet there has been no research examining the ways in which the
thyroid cancers of WTC first responders differ biologically from the non-WTC exposed cohort,
especially in terms of the aggressiveness of the tumors.
In vitro exposure of rats to WTC dust has been shown to be associated with inflammatory
reactions in distant organs. Furthermore, prostate cancer tissue from WTC responders showed
a distinct pattern of gene expression, with downregulation of genes involved in innate immunity
response and an upregulation of genes related to apoptosis, suggesting that inflammation
caused by the inhalation of WTC dust may act as a tumor promoter. Using a 770 gene panel
developed by Nanostring, we will characterize the inflammatory and immune microenvironment
both in the thyroids of rats directly exposed to WTC dust (aim 1) and tissue from 30 formalin-
fixed paraffin-embedded (FFPE) WTC thyroid tumor slides compared to 30 non-WTC exposed
cases (aim 2).
We will also use whole exome sequencing to look at the genetic alterations driving WTC thyroid
cancer development as compared to non WTC exposed cases (aim 3). Specifically we will
compare the number of multiple driver mutations as well as mutations validated as more
aggressive between the two groups. We will also look for novel driver mutations in the WTC
group that may be targets for treatment.
This project would represent the first in-depth analysis of the presence of an “inflammatory
microenvironment” in animal thyroid tissue and human thyroid cancer tissue after the inhalation
of WTC dust. Linkage of the presence of these markers of inflammation with genetic alterations
showing WTC thyroid cancer cases to more aggressive would have implications for the
treatment of WTC first responders, justifying an active treatment approach, including surgery,
for the WTC thyroid cancer patient population.

## Key facts

- **NIH application ID:** 9984885
- **Project number:** 5U01OH011849-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** GREGORY Joseph RIGGINS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2020
- **Award amount:** $999,987
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984885

## Citation

> US National Institutes of Health, RePORTER application 9984885, Thyroid Cancer Aggressiveness in WTC Responders (5U01OH011849-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984885. Licensed CC0.

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