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Grant Details

Grant Number: 5R00CA277580-04 Interpret this number
Primary Investigator: Collin, Lindsay
Organization: Emory University
Project Title: Identifying Factors Associated with Ovarian Cancer Recurrence Using a Population-Based Approach
Fiscal Year: 2026


Abstract

Prostate cancer (PCa) is responsible for one of the greatest cancer health disparities, with African-American (AA) men experiencing a death rate 2.4 times higher than that for EA men, which accounts for nearly 40% of the total overall cancer mortality disparity between AA and EA men. PCa mortality is largely due to metastases, and thus it is critical to understand the disparities in the mechanisms of metastasis. Our preliminary studies have shown that genes related to oxidative phosphorylation (OXPHOS) are enriched in PCa tumors from AA men relative to EA men, as well as between normal tissue, primary tumors, and LNM. FGFR3 is a fibroblast growth factor tyrosine kinase receptor that binds to fibroblast growth factor ligands and activates OXPHOS, PI3K/AKT, STAT, RAS/MAPK, and ERK signaling pathways. We have also discovered splice site mutations in FGFR3 that are present in both primary tumor foci and LNM and have shown that FGFR3 mutations are more frequent in metastases than primary tumors examining data from over 6500 samples. We have also determined that FGFR3 expression is significantly correlated with % African ancestry in TCGA patients, and we have identified three SNPs in the FGFR3 enhancer with >40% allele frequency differences in AA populations. Moreover, FGFR3 expression was significantly higher in our datasets of prostate tumors from AA men than from EA men. We hypothesize that the OXPHOS pathway and FGFR3 signaling play important roles in metastasis. We plan to test this hypothesis via the following Specific Aims: Aim 1. To analyze differential pathway activity in independent patient cohorts. We hypothesize that FGFR3 and OXPHOS genes will be associated with metastasis. We will confirm and validate our preliminary findings examining prostatectomies, circulating tumor cell clusters, and metastatic biopsies. Aim 2. To analyze the impact of perturbation of FGFR3 signaling on metastasis using in vitro and in vivo models of prostate cancer. We hypothesize that increased FGFR3 expression and/or FGFR3 mutations may activate OXPHOS activity, promoting metastasis. We will investigate the mechanisms of regulation of FGFR3 expression and the impact of these novel mutations. Aim 3. To determine the effect of perturbation of OXPHOS on the metastatic potential of prostate cancer cell lines in vitro and in vivo. We hypothesize that OXPHOS activity promotes metastasis in PCa. We will manipulate OXPHOS activity to understand how it impacts metastasis in models of PCa. Completion of these studies will provide new insights into PCa metastasis, demonstrate the potential clinical utility of FGFR3 and/or OXPHOS inhibitors, and could ultimately help reduce cancer health disparities.



Publications

The KPROCS Study: A Real-World and Research Resource to Investigate Multilevel Determinants of Ovarian Cancer Treatment and Survival.
Authors: Bandera E.V. , Doherty J.A. , Lee V.S. , Collin L.J. , Kavecansky J. , Khosrow-Khavar F. , Li J. , Moy L.M. , Chirikova E. , Inamdar P.P. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2026-08-31 00:00:00.0; , .
EPub date: 2026-08-31 00:00:00.0.
PMID: 42671158
Related Citations

Genetic ancestry and risk of atrial fibrillation in individuals of Black ethnicity in the UK Biobank.
Authors: Liu C. , Sun Y.V. , Li L. , Collin L.J. , Shah A.J. , Alonso A. .
Source: Open Heart, 2026-07-31 00:00:00.0; 13(2), .
EPub date: 2026-07-31 00:00:00.0.
PMID: 42538060
Related Citations

Neighborhood deprivation and oncotype DX recurrence scores among Black and White women: the interplay between race, place, and tumor biology.
Authors: Miller-Kleinhenz J.M. , Barber L.E. , Maliniak M.L. , Collin L.J. , Smith-Graziani D.J. , Switchenko J.M. , Ward K.C. , McCullough L.E. .
Source: Npj Breast Cancer, 2026-05-30 00:00:00.0; , .
EPub date: 2026-05-30 00:00:00.0.
PMID: 42218146
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Transcriptomic subtypes in high-grade serous ovarian cancer are driven by tumor cellular composition.
Authors: Tanis S. , Lixandrão M. , Ivich A. , Grieshober L. , Lawson-Michod K.A. , Collin L.J. , Peres L.C. , Salas L.A. , Marks J.R. , Bitler B.G. , et al. .
Source: Biorxiv : The Preprint Server For Biology, 2026-04-21 00:00:00.0; , .
EPub date: 2026-04-21 00:00:00.0.
PMID: 42079185
Related Citations

Why Validation Substudies Matter.
Authors: Collin L.J. , Stanhope K.K. .
Source: Paediatric And Perinatal Epidemiology, 2026-02-25 00:00:00.0; , .
EPub date: 2026-02-25 00:00:00.0.
PMID: 41741353
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Diminishing Returns Among Black Patients With Cancer: The Intersection of Race and Neighborhood Socioeconomic Status.
Authors: McCullough L.E. , Barber L.E. , Nash R. , Collin L.J. , Maliniak M.L. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2026-02-02 00:00:00.0; , p. JCO2501038.
EPub date: 2026-02-02 00:00:00.0.
PMID: 41628392
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Association of Race, Ethnicity, and Area Deprivation With the Prevalence of Atrial Fibrillation in a Large US Population.
Authors: Alonso A. , Najarro G. , Shah A.J. , Li L. , Lewis T.T. .
Source: Circulation. Arrhythmia And Electrophysiology, 2025-12-31 00:00:00.0; , p. e014197.
EPub date: 2025-12-31 00:00:00.0.
PMID: 41473962
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Homologous recombination deficiency and survival in ovarian high-grade serous carcinoma by self-reported race.
Authors: Lawson-Michod K.A. , Johnson C.E. , Barnard M.E. , Davidson N.R. , Collin L.J. , Nix D.A. , Huff C.D. , Berchuck A. , Salas L.A. , Greene C.S. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2025-09-04 00:00:00.0; , .
EPub date: 2025-09-04 00:00:00.0.
PMID: 40905821
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Tattooing and risk of melanoma: a population-based case-control study in Utah.
Authors: McCarty R.D. , Trabert B. , Collin L.J. , Millar M.M. , Kriebel D. , Grieshober L. , Barnard M.E. , Sawatzki J. , Carter M. , Yoder V. , et al. .
Source: Journal Of The National Cancer Institute, 2025-08-21 00:00:00.0; , .
EPub date: 2025-08-21 00:00:00.0.
PMID: 40839395
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Cancer in persons diagnosed with facial nerve paresis: A hospital-based cohort study in Denmark.
Authors: Elser H. , Farkas D.K. , Collin L.J. , Lykke M.R. , Fuglsang C.H. , Sørensen H.T. .
Source: Cancer Epidemiology, 2025 Aug; 97, p. 102863.
EPub date: 2025-06-11 00:00:00.0.
PMID: 40505214
Related Citations

Genetic Ancestry and Risk of Atrial Fibrillation in Individuals of Black Ethnicity in the UK Biobank.
Authors: Liu C. , Sun Y.V. , Li L. , Collin L.J. , Shah A.J. , Alonso A. .
Source: Medrxiv : The Preprint Server For Health Sciences, 2025-07-14 00:00:00.0; , .
EPub date: 2025-07-14 00:00:00.0.
PMID: 40791710
Related Citations

Nondifferential misclassification of outcome under (near-) perfect specificity: a simulation study.
Authors: Ma W. , MacLehose R.F. , Lash T.L. , Collin L.J. , Tuo Y. , Ahern T.P. .
Source: American Journal Of Epidemiology, 2025-06-03 00:00:00.0; 194(6), p. 1668-1672.
PMID: 39245702
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Genetic variants in tamoxifen metabolism and early treatment discontinuation among premenopausal breast cancer patients.
Authors: Woolpert K.M. , Ahern T.P. , Baurley J.W. , Maliniak M.L. , Damkier P. , Kjærsgaard A. , Collin L.J. , Hamilton-Dutoit S. , Tramm T. , Ejlertsen B. , et al. .
Source: Breast Cancer Research And Treatment, 2025-05-14 00:00:00.0; , .
EPub date: 2025-05-14 00:00:00.0.
PMID: 40369345
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Perceived discrimination, trust in physicians, and their associations with ovarian cancer mortality among women in the African American Cancer Epidemiology Study.
Authors: Collin L.J. , Johnson C.E. , Akonde M. , Kan M. , Bandera E.V. , Peres L.C. , Qin B. , Cote M.L. , Alberg A. , Peters E.S. , et al. .
Source: Cancer Causes & Control : Ccc, 2025-05-06 00:00:00.0; , .
EPub date: 2025-05-06 00:00:00.0.
PMID: 40327211
Related Citations

Perceived discrimination, trust in physicians, and their associations with ovarian cancer mortality among women in the African American Cancer Epidemiology Study.
Authors: Collin L.J. , Johnson C.E. , Akonde M. , Kan M. , Bandera E.V. , Peres L.C. , Qin B. , Cote M.L. , Alberg A. , Peters E.S. , et al. .
Source: Cancer Causes & Control : Ccc, 2025-05-06 00:00:00.0; , .
EPub date: 2025-05-06 00:00:00.0.
PMID: 40327211
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Adjusting Adjustments: Using External Data to Estimate the Impact of Different Confounder Sets on Published Associations.
Authors: Ahern T.P. , Collin L.J. , MacLehose R.F. , Littenberg B. , Haines L. , Bonnett M. , Asmussen F.B. , Chen J. , Lash T.L. .
Source: Epidemiology (cambridge, Mass.), 2025-05-01 00:00:00.0; 36(3), p. 381-390.
EPub date: 2024-11-22 00:00:00.0.
PMID: 39575936
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Drug Interactions With Tamoxifen and Treatment Effectiveness in Premenopausal Breast Cancer Patients: A Bayesian Joint Modeling Approach.
Authors: Woolpert K.M. , Cronin-Fenton D.P. , Damkier P. , Kjærsgaard A. , Hamilton-Dutoit S. , Ejlertsen B. , MacLehose R.F. , Christiansen P. , Silliman R.A. , Lash T.L. , et al. .
Source: Pharmacoepidemiology And Drug Safety, 2025 May; 34(5), p. e70157.
PMID: 40364655
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Parameterization of Beta Distributions for Bias Parameters of Binary Exposure Misclassification in Probabilistic Bias Analysis.
Authors: Zhang Q. , MacLehose R.F. , Collin L.J. , Ahern T.P. , Lash T.L. .
Source: Epidemiology (cambridge, Mass.), 2025-03-01 00:00:00.0; 36(2), p. 237-244.
EPub date: 2024-11-26 00:00:00.0.
PMID: 39588976
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Patterns of associations with epidemiologic factors by high grade serous ovarian cancer gene expression subtypes.
Authors: Collin L.J. , Cushing-Haugen K.L. , Terry K.L. , Goode E.L. , Wu A.H. , Harris H.R. , Sasamoto N. , Cramer D.W. , Modugno F. , Elishaev E. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2025-02-26 00:00:00.0; , .
EPub date: 2025-02-26 00:00:00.0.
PMID: 40009771
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CYP2D6 Phenotype and Breast Cancer Outcomes: A Bias Analysis and Meta-Analysis.
Authors: MacLehose R.F. , Ahern T.P. , Collin L.J. , Li A. , Lash T.L. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2025-02-06 00:00:00.0; 34(2), p. 224-233.
PMID: 39540781
Related Citations

Homologous recombination deficiency in ovarian high-grade serous carcinoma by self-reported race.
Authors: Lawson-Michod K.A. , Johnson C.E. , Barnard M.E. , Davidson N. , Collin L.J. , Nix D.A. , Huff C. , Berchuck A. , Salas L.A. , Greene C. , et al. .
Source: Medrxiv : The Preprint Server For Health Sciences, 2025-01-28 00:00:00.0; , .
EPub date: 2025-01-28 00:00:00.0.
PMID: 39974072
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A registry-based approach for estimating county-level race disparities in breast cancer mortality: an analysis in Georgia.
Authors: Nash R. , Switchenko J.M. , Ward K.C. , Maliniak M.L. , Collin L.J. , Moubadder L. , Kramer M.R. , Lash T.L. , Gaglioti A. , Bayakly R. , et al. .
Source: American Journal Of Epidemiology, 2025-01-10 00:00:00.0; , .
EPub date: 2025-01-10 00:00:00.0.
PMID: 39801014
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Comorbid conditions and survival among Black women with ovarian cancer.
Authors: Richards A.R. , Johnson C.E. , Montalvo N.R. , Alberg A.J. , Bandera E.V. , Bondy M. , Collin L.J. , Cote M.L. , Hastert T.A. , Haller K. , et al. .
Source: Cancer, 2025-01-01 00:00:00.0; 131(1), p. e35694.
PMID: 39748467
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The role of multiple mediation with contextual neighborhood measures in ovarian cancer survival.
Authors: Lawson A.B. , Xin Y. , Peters E.S. , Johnson C. , Hastert T. , Bandera E.V. , Alberg A.J. , Collin L. , Terry P. , Akonde M. , et al. .
Source: Annals Of Epidemiology, 2024 Nov; 99, p. 41-46.
EPub date: 2024-10-09 00:00:00.0.
PMID: 39389398
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Sociodemographic and Socioeconomic Factors Correlate with Late-Stage Pediatric Hodgkin Lymphoma and Rhabdomyosarcoma: A Report from the Children's Oncology Group Registries.
Authors: Ou J.Y. , Kaddas H.K. , Alonzo T.A. , Spector L.G. , Fallahazad N. , Owens E. , Collin L.J. , Green A.L. , Kirchhoff A.C. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2024-10-02 00:00:00.0; 33(10), p. 1327-1338.
PMID: 39083086
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Diet and Survival in Black Women With Epithelial Ovarian Cancer.
Authors: Armidie T.A. , Bandera E.V. , Johnson C.E. , Peres L.C. , Haller K. , Terry P. , Akonde M. , Peters E.S. , Cote M.L. , Hastert T.A. , et al. .
Source: Jama Network Open, 2024-10-01 00:00:00.0; 7(10), p. e2440279.
EPub date: 2024-10-01 00:00:00.0.
PMID: 39422908
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Tattoos and Risk of Hematologic Cancer: A Population-Based Case-Control Study in Utah.
Authors: McCarty R.D. , Trabert B. , Kriebel D. , Millar M.M. , Birmann B.M. , Grieshober L. , Barnard M.E. , Collin L.J. , Lawson-Michod K.A. , Gibson B. , et al. .
Source: Cancer Medicine, 2024 Oct; 13(20), p. e70260.
PMID: 39444249
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The Population-level Effect of Adjuvant Therapies on Breast Cancer Recurrence: Application of the Trend-in-Trend Design.
Authors: Collin L.J. , Waller L.A. , Cronin-Fenton D.P. , Ahern T.P. , Goodman M. , McCullough L.E. , Kjærsgaard A. , Woolpert K.M. , Silliman R.A. , Christiansen P.M. , et al. .
Source: Epidemiology (cambridge, Mass.), 2024-09-01 00:00:00.0; 35(5), p. 660-666.
EPub date: 2024-08-06 00:00:00.0.
PMID: 39109817
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Associations of demographic, health, and risk-taking behaviors with tattooing in a population-based cross-sectional study of ~18,000 US adults.
Authors: McCarty R.D. , Trabert B. , Millar M.M. , Kriebel D. , Grieshober L. , Barnard M.E. , Collin L.J. , Lawson-Michod K.A. , Gibson B. , Gilreath J.A. , et al. .
Source: Research Square, 2024-08-28 00:00:00.0; , .
EPub date: 2024-08-28 00:00:00.0.
PMID: 39257981
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Racial disparities in initiation of chemotherapy among breast cancer patients with discretionary treatment indication in the state of Georgia.
Authors: Collin L.J. , Jones J. , Nash R. , Switchenko J.M. , Ward K.C. , McCullough L.E. .
Source: Breast Cancer Research And Treatment, 2024 Jun; 205(3), p. 609-618.
EPub date: 2024-03-22 00:00:00.0.
PMID: 38517602
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Unravelling race inequities in cardiovascular disease mortality among cancer survivors: new insights and future directions.
Authors: McCullough L.E. , Collin L.J. , Statman M. .
Source: International Journal Of Epidemiology, 2024-04-11 00:00:00.0; 53(3), .
PMID: 38684341
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Clinical factors associated with patterns of endocrine therapy adherence in premenopausal breast cancer patients.
Authors: Woolpert K.M. , Schmidt J.A. , Ahern T.P. , Hjorth C.F. , Farkas D.K. , Ejlertsen B. , Collin L.J. , Lash T.L. , Cronin-Fenton D.P. .
Source: Breast Cancer Research : Bcr, 2024-04-08 00:00:00.0; 26(1), p. 59.
EPub date: 2024-04-08 00:00:00.0.
PMID: 38589932
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Association of inflammation-related exposures and ovarian cancer survival in a multi-site cohort study of Black women.
Authors: Johnson C.E. , Alberg A.J. , Bandera E.V. , Peres L.C. , Akonde M. , Collin L.J. , Cote M.L. , Hastert T.A. , Hébert J.R. , Peters E.S. , et al. .
Source: British Journal Of Cancer, 2023-08-03 00:00:00.0; , .
EPub date: 2023-08-03 00:00:00.0.
PMID: 37537254
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Associations between health insurance status, neighborhood deprivation, and treatment delays in women with breast cancer living in Georgia.
Authors: Awan S. , Saini G. , Gogineni K. , Luningham J.M. , Collin L.J. , Bhattarai S. , Aneja R. , Williams C.P. .
Source: Cancer Medicine, 2023 Aug; 12(16), p. 17331-17339.
EPub date: 2023-07-12 00:00:00.0.
PMID: 37439033
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Disparities in ovarian cancer survival: does place matter?
Authors: Gomez S.L. , Mcguire V. , Collin L.J. , Dempsey L. , Inamdar P. , Lawson-Michod K. , Peters E.S. , Kushi L. , Shariff-Marco S. , Peres L. , et al. .
Source: American Journal Of Obstetrics And Gynecology, 2023-04-26 00:00:00.0; , .
EPub date: 2023-04-26 00:00:00.0.
PMID: 37116824
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Understanding gastrointestinal cancer mortality disparities in a racially and geographically diverse population.
Authors: Nash R. , Russell M.C. , Miller-Kleinhenz J.M. , Collin L.J. , Ross-Driscoll K. , Switchenko J.M. , McCullough L.E. .
Source: Cancer Epidemiology, 2022 Apr; 77, p. 102110.
EPub date: 2022-02-07 00:00:00.0.
PMID: 35144126
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