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

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data:
  list_of_additional_authors:
    - add_author_degrees: PhD
      affiliation: 'Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA'
      first_name: Devendra
      last_name: Paudel
    - add_author_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
    - add_author_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
    - add_author_degrees: ''
      affiliation: 'Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA'
      first_name: 'Catherine '
      last_name: Mullins
    - add_author_degrees: ''
      affiliation: 'Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA'
      first_name: 'Aryan '
      last_name: Patel
    - add_author_degrees: PhD
      affiliation: 'Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA'
      first_name: Douglas
      last_name: Walker
    - add_author_degrees: PhD
      affiliation: 'Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA'
      first_name: Elizabeth
      last_name: Platz
    - add_author_degrees: PhD
      affiliation: 'Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA'
      first_name: Cynthia
      last_name: Sears
    - add_author_degrees: PhD
      affiliation: 'Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA'
      first_name: Kala
      last_name: Visvanathan
    - add_author_degrees: PhD
      affiliation: 'Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA'
      first_name: Marsha
      last_name: Wills-Karp
    - add_author_degrees: PhD
      affiliation: 'Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA'
      first_name: Brian
      last_name: Huang
    - add_author_degrees: PhD
      affiliation: 'Department of Biostatistics & Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA'
      first_name: 'David '
      last_name: Conti
    - add_author_degrees: PhD
      affiliation: 'Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA'
      first_name: Lida
      last_name: Chatzi
    - add_author_degrees: PhD
      affiliation: 'Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA'
      first_name: Tanya
      last_name: Alderete
  degree_s_: Ph.D
  email: dpaudel1@jh.edu
  first_name: Devendra
  last_name: Paudel
  middle_initial: ''
  organization: 'Johns Hopkins University'
  summary: |-
    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.
  title: 'NIH T32 Post-doctoral scholar'
  ttile: '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'