Faculty Collaboration Database

Association of Genetic Predisposition to Inflammation With Cancer-Related Cognitive Impairment and Fatigue in Women Who Received Chemotherapy for Nonmetastatic Breast Cancer. JCO Precis Oncol 2025 Sep;9:e2500303

Date

09/16/2025

Pubmed ID

40956996

Pubmed Central ID

PMC12442773

DOI

10.1200/PO-25-00303

Scopus ID

2-s2.0-105030959302 (requires institutional sign-in at Scopus site)

Abstract

PURPOSE: Cancer-related cognitive impairment (CRCI) and cancer-related fatigue (CRF) are reported by approximately 75% of patients receiving chemotherapy for breast cancer and both have been linked to inflammation. We sought to test whether an inflammation polygenic risk score (iPRS) might be associated with CRCI and/or CRF.

METHODS: Using data from the UK Biobank, we developed an iPRS for the INFLA-Score, a composite measure of C-reactive protein, white cell count, platelet count, and neutrophil-lymphocyte ratio. The iPRS was evaluated for association with CRCI and CRF among women with nonmetastatic breast cancer enrolled in two completed multisite clinical trials: URCC08106 and URCC10055. CRCI and CRF were measured before and after standard-of-care chemotherapy using the FACT-Cog and Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), respectively. Linear regression evaluated the change in FACT-Cog and MFSI scores; logistic regression evaluated binary outcomes of any versus no worsening of scores. Analyses were adjusted for patient and treatment factors. We also performed exploratory genome-wide analyses.

RESULTS: The cohort included 802 women who received chemotherapy (anthracycline-based = 51.8%; previous surgery = 85.0%) at a median age of 55 years (range = 22-81). The iPRS was associated with a significant decrease in MFSI-SF score (β = -3.29 [95% CI, -6.25 to -0.34]; P = .029) and lower odds of decreased MFSI-SF score (odds ratio, 0.66 [95% CI, 0.47 to 0.93]; P = .016) following chemotherapy. This negative relationship was partially explained by a positive correlation of the iPRS with prechemotherapy MFSI-SF score (β = 4.33 [95% CI, 0.23 to 8.43]; P = .038). The iPRS was not associated with a change in FACT-Cog score (β = -1.12; P = .627), but single nucleotide polymorphism rs9365961 was (β = -10.05; P = 1.46 × 10^-8).

CONCLUSION: If validated, the iPRS could identify patients in need of supportive care interventions to reduce CRF.

Author List

Olowofela AS, Auer PL, Janelsins M, Mustian K, Conlin A, Onitilo AA, Melnik M, Li CS, Gada U, Sun H, Kerns SL

Authors

Paul L. Auer PhD Professor in the Data Science Institute department at Medical College of Wisconsin
Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Breast Neoplasms
Fatigue
Female
Genetic Predisposition to Disease
Humans
Inflammation
Middle Aged