# Multi-Pathway DNA Repair Capacity Measurements in Lung Cancer Patients and Healthy Controls

> **NIH NIH U01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2021 · $612,996

## Abstract

Project Summary
Environmental, medical, and endogenously produced DNA damaging agents are ubiquitous, yet, for a given
exposure only a subset of individuals experience health effects. This proposal focuses on non-small cell lung
cancer (NSCLC) and clinical sensitivity to radiation, a therapeutic agent used to treat NSCLC. These represent
two major health effects associated with exposure DNA damage. Our goal is to identify possible markers in blood
lymphocytes that can predict NSCLC risk, or the severity of side effects to radiation therapy. It is clear that
individuals vary in their capacity to repair DNA lesions, and inefficient DNA repair is a risk factor for cancer and
other diseases. However it has thus far not been feasible to use measurements of DNA repair capacity to predict
disease risk or acute sensitivity to a particular exposure (such as radiation), because the methods available for
measuring DNA repair have not been amenable to making comprehensive assessments of genomic integrity in
human populations. Furthermore, efforts to understand inter-individual differences using genomics approaches,
such as transcriptional profiling and genome wide genotyping, leave unanswered questions regarding the
functional ramifications of the genomic signatures that are identified. We will therefore combine cutting edge
technologies for making functional assessments of DNA repair capacity in all of the major pathways with
transcriptional profiling and genome wide genotyping to make a comprehensive analysis of genomic integrity in
lung cancer patients undergoing radiation therapy and in healthy controls. Lung cancer patients represent a key
population of individuals whose disease is often caused by exposure to DNA damaging agents, and has been
associated with aberrant DNA repair capacity in multiple pathways, each in separate, previous population
studies. Furthermore, treatment with radiation is a defined in vivo human exposure to a complex mixture of DNA
damage that provides an opportunity to identify biomarkers that could predict individual sensitivity to DNA
damaging agents. Our study is distinguished from previous work by the integration of new functional assays
with genomic data. We expect to identify new genomic integrity biomarkers that may predict the radiation dose
an individual patient can safely tolerate, as well as biomarkers that may open the door to personalized cancer
prevention and surveillance strategies based on identifying individuals who are more likely to develop NSCLC.
Because radiation and other DNA damaging agents are a key component of therapy for a wide variety of cancers,
and because cancer susceptibility at many sites has been associated with a failure to maintain genomic integrity,
the results of this study are likely to be generalizable well beyond the immediate context of non-small cell lung
cancer.

## Key facts

- **NIH application ID:** 10228767
- **Project number:** 5U01ES029520-04
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** David C Christiani
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $612,996
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228767

## Citation

> US National Institutes of Health, RePORTER application 10228767, Multi-Pathway DNA Repair Capacity Measurements in Lung Cancer Patients and Healthy Controls (5U01ES029520-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10228767. Licensed CC0.

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