Ayokunle S Olowofela, Paul L Auer, Michelle Janelsins, Karen Mustian, Alison Conlin, Adedayo A Onitilo, Marianne Melnik, Chin-Shang Li, Umang Gada, Hongying Sun, Sarah L Kerns
{"title":"在接受非转移性乳腺癌化疗的女性中，炎症遗传易感性与癌症相关的认知障碍和疲劳的关联","authors":"Ayokunle S Olowofela, Paul L Auer, Michelle Janelsins, Karen Mustian, Alison Conlin, Adedayo A Onitilo, Marianne Melnik, Chin-Shang Li, Umang Gada, Hongying Sun, Sarah L Kerns","doi":"10.1200/PO-25-00303","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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]; <i>P</i> = .029) and lower odds of decreased MFSI-SF score (odds ratio, 0.66 [95% CI, 0.47 to 0.93]; <i>P</i> = .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]; <i>P</i> = .038). The iPRS was not associated with a change in FACT-Cog score (β = -1.12; <i>P</i> = .627), but single nucleotide polymorphism rs9365961 was (β = -10.05; <i>P</i> = 1.46 × 10<sup>-8</sup>).</p><p><strong>Conclusion: </strong>If validated, the iPRS could identify patients in need of supportive care interventions to reduce CRF.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500303"},"PeriodicalIF":5.6000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442773/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of Genetic Predisposition to Inflammation With Cancer-Related Cognitive Impairment and Fatigue in Women Who Received Chemotherapy for Nonmetastatic Breast Cancer.\",\"authors\":\"Ayokunle S Olowofela, Paul L Auer, Michelle Janelsins, Karen Mustian, Alison Conlin, Adedayo A Onitilo, Marianne Melnik, Chin-Shang Li, Umang Gada, Hongying Sun, Sarah L Kerns\",\"doi\":\"10.1200/PO-25-00303\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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]; <i>P</i> = .029) and lower odds of decreased MFSI-SF score (odds ratio, 0.66 [95% CI, 0.47 to 0.93]; <i>P</i> = .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]; <i>P</i> = .038). The iPRS was not associated with a change in FACT-Cog score (β = -1.12; <i>P</i> = .627), but single nucleotide polymorphism rs9365961 was (β = -10.05; <i>P</i> = 1.46 × 10<sup>-8</sup>).</p><p><strong>Conclusion: </strong>If validated, the iPRS could identify patients in need of supportive care interventions to reduce CRF.</p>\",\"PeriodicalId\":14797,\"journal\":{\"name\":\"JCO precision oncology\",\"volume\":\"9 \",\"pages\":\"e2500303\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442773/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JCO precision oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/PO-25-00303\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCO precision oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/PO-25-00303","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Association of Genetic Predisposition to Inflammation With Cancer-Related Cognitive Impairment and Fatigue in Women Who Received Chemotherapy for Nonmetastatic Breast Cancer.
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.
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