# L1 element mutagenesis as a driver of epithelial cancers in African Americans

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $216,686

## Abstract

Project Summary.
 LINE-1 (L1) elements are endogenous mobile elements that can replicate themselves and insert new
copies throughout the human genome. When they are inserted into coding exons or other functionally
important sites in genes, they can cause human diseases, including cancers. Although functional L1 “source”
elements are typically silenced by methylation in adult somatic tissues, a number of L1 source elements have
been identified that can evade somatic repression and generate new L1 insertions in tumor suppressor genes
and oncogenes. For example, we identified a highly active L1 source element that evaded somatic repression
in normal colon tissues and initiated colorectal cancer (CRC) by mutating the APC tumor suppressor gene in
an African American patient. Importantly, we found that this source element was only found in African and
African-diaspora populations (including African Americans), suggesting that it may pose a unique cancer risk to
these populations. We also identified another similar element that evaded somatic repression and generated
additional somatic L1 insertions in the tumor of this patient. This second element also was only found in
African and African-diaspora populations (including African Americans). In this proposal, we will test the
hypothesis that these two highly active L1 source elements (and other L1 elements like them) increase the risk
for African Americans to develop CRC compared to White control cohorts who lack these elements. We also
will examine the methylation status and expression of these elements in African American CRCs to explore the
mechanism(s) by which they evade somatic repression. Overall, these studies will allow us to evaluate the
cancer risk that is posed by these population-specific L1 source elements to African Americans.

## Key facts

- **NIH application ID:** 10350837
- **Project number:** 1R21CA259309-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Scott E Devine
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $216,686
- **Award type:** 1
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350837

## Citation

> US National Institutes of Health, RePORTER application 10350837, L1 element mutagenesis as a driver of epithelial cancers in African Americans (1R21CA259309-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10350837. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*