Annual Meeting of the NCI Cohort Consortium (Abstract Submission): Submission #5

Submission information
Submission Number: 5
Submission ID: 186265
Submission UUID: 7547b2ef-320f-4604-87a3-64f4cf542a41

Created: Fri, 07/10/2026 - 12:21
Completed: Fri, 07/10/2026 - 12:47
Changed: Fri, 07/10/2026 - 12:47

Remote IP address: 10.208.24.52
Submitted by: Anonymous
Language: English

Is draft: No
First Name Devendra
Middle Initial
Last Name Paudel
Degree(s) Ph.D
Position/Title/Career Status NIH T32 Post-doctoral scholar
Organization Johns Hopkins University
Email dpaudel1@jh.edu
List of Additional Authors
  • First Name: Devendra
    Last Name: Paudel
    Degrees: PhD
    Affiliation: Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • First Name: Haonan
    Last Name: Li
    Degrees: PhD
    Affiliation: Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • First Name: Daisy
    Last Name: Brumit
    Degrees: PhD
    Affiliation: Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • First Name: Catherine
    Last Name: Mullins
    Affiliation: Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
  • First Name: Aryan
    Last Name: Patel
    Affiliation: Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
  • First Name: Douglas
    Last Name: Walker
    Degrees: PhD
    Affiliation: Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
  • First Name: Elizabeth
    Last Name: Platz
    Degrees: PhD
    Affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • First Name: Cynthia
    Last Name: Sears
    Degrees: PhD
    Affiliation: Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • First Name: Kala
    Last Name: Visvanathan
    Degrees: PhD
    Affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • First Name: Marsha
    Last Name: Wills-Karp
    Degrees: PhD
    Affiliation: Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • First Name: Brian
    Last Name: Huang
    Degrees: PhD
    Affiliation: Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • First Name: David
    Last Name: Conti
    Degrees: PhD
    Affiliation: Department of Biostatistics & Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
  • First Name: Lida
    Last Name: Chatzi
    Degrees: PhD
    Affiliation: Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • First Name: Tanya
    Last Name: Alderete
    Degrees: PhD
    Affiliation: Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Abstract Title Prediagnostic plasma per- and polyfluoroalkyl substances and colorectal cancer risk: a nested case-control study in the CLUE II cohort stratified by time to diagnosis
Abstract Background
Epidemiologic evidence linking per- and polyfluoroalkyl substances (PFAS) to colorectal cancer (CRC) is inconsistent, despite IARC classification of PFOA as a human carcinogen and PFOS as a possible human carcinogen. Most prior studies measured PFAS at or near diagnosis, where subclinical disease may have altered circulating concentrations, limiting interpretation of observed associations.

Methods
Within the CLUE II prospective cohort (1989 baseline), we measured 38 plasma PFAS by LC-HRMS in 208 incident CRC cases (1989–2003) and 208 matched controls (age, sex, race, smoking, BMI). Fifteen PFAS with ≥70% detection were included in continuous analyses. The prespecified primary analysis tested whether the PFAS–CRC association varied with time from blood collection to diagnosis (PFAS × time interaction). Secondary analyses evaluated individual PFAS with Benjamini-Hochberg false discovery rate correction (q < 0.05) and tumor subsite. Biomarker reduction was assessed in an independent postdiagnostic cohort of early-onset (EAO; n = 75) and late-onset (LAO; n = 79) CRC cases.

Results
Sum total PFAS showed a significant PFAS × time interaction (p = 0.002): the model-estimated odds ratio (OR) per log₂ doubling increased from 0.49 (95% CI 0.30–0.79) at 2 years to 1.63 (95% CI 1.03–2.59) at 12 years before diagnosis, crossing the null at approximately 8 years. Fourteen of 15 individual PFAS had OR > 1 at 12 years (binomial p = 0.0005); five reached FDR significance (PFOA, PFHpS, PFECHS, PFHxS, PFOS; q < 0.05). Associations were directionally consistent across tumor subsites. In the postdiagnostic EAO/LAO cohort, PFAS concentrations were lower than contemporaneous NHANES reference values (2017–2020), consistent with disease-related biomarker reduction.

Conclusions
Prediagnostic plasma PFAS concentrations were positively associated with CRC risk at long prediagnostic intervals and inversely associated at short intervals, consistent with biomarker reduction near diagnosis. These findings highlight the importance of measurement timing and warrant confirmation in larger prospective cohorts.