Polygenic risk scores in assessing lung cancer susceptibility in non-Hispanic White and Black populations.

Authors

null

Matthew R Trendowski

Wayne State University School of Medicine, Detroit, MI

Matthew R Trendowski , Chrissy Lusk , Angie Wenzlaff , Christine Neslund-Dudas , Shirish M. Gadgeel , Ayman Soubani , Ann G. Schwartz

Organizations

Wayne State University School of Medicine, Detroit, MI, Karmanos Cancer Institute, Wayne State University, Detroit, MI, Karmanos Cancer Institute, Detroit, MI, Henry Ford Health, Detroit, MI, Division of Hematology/Oncology, Henry Ford Health System, Detroit, MI, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI

Research Funding

U.S. National Institutes of Health
U.S. National Institutes of Health, Herrick Foundation

Background: Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black patients in model development. We used previously identified single nucleotide polymorphisms (SNPs) and annotated SNPs in associated gene regions to develop PRS in non-Hispanic Whites and Blacks using the INHALE dataset. Methods: Using the Multi-Ethnic Genotype Array, 1,204 SNPs for non-Hispanic Whites and 1,515 SNPs for Blacks were evaluated for their association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of COPD and the top five PCs for genetic ancestry. Gene region-specific significant SNPs (p < 0.05) were used to develop race-specific PRS. Results: The race-specific PRS included different sets of significant SNPs and were highly associated with lung cancer risk in both non-Hispanic Whites (OR = 1.07, 95% CI: 1.05-1.09, p = 3.44x10-9) and Blacks (OR = 1.12, 95% CI: 1.08-1.17, p = 9.14x10-8). These models remained significant for both Whites (OR = 1.05, 95% CI: 1.03-1.09, p = 0.0004) and Blacks (OR = 1.08, 95% CI: 1.01-1.15, p = 0.01) who currently do not meet USPSTF screening guidelines. AUC analysis demonstrated the Black-specific model (AUC = 0.68) outperformed the White-specific model (AUC = 0.57) (p = 0.03) when examined exclusively in the Black cohort. Conclusions: Using previously validated SNPs and gene regions, we developed race-specific PRS in non-Hispanic White and Black INHALE participants. Further validation of PRS could enable the incorporation of genetic risk modeling into lung cancer screening to identify patients who do not have traditional risk factors for lung cancer, as well as stratify patients into different levels of risk based on their genetic profile. Through the development of a reliable genetic risk factor prediction model, clinicians will have another method by which to evaluate lung cancer susceptibility, potentially leading to earlier diagnoses that portend more favorable treatment outcomes.

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Prevention, Risk Reduction, and Hereditary Cancer

Track

Prevention, Risk Reduction, and Genetics

Sub Track

Germline Genetic Testing

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 10548)

DOI

10.1200/JCO.2023.41.16_suppl.10548

Abstract #

10548

Poster Bd #

181

Abstract Disclosures

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