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

Presenter Information
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First Name: Devendra
Middle Initial: {Empty}
Last Name: Paudel
Degree(s): Ph.D
Position/Title/Career Status: NIH T32 Post-doctoral scholar
Organization: Johns Hopkins University
Email: dpaudel1@jh.edu

Additional Authors
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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 Information
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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.