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Associations between plasma ANGPTL4 levels and the risk of 24 cancers: a prospective cohort study.

Xi Cheng1, Shuzhen Zhao2, Mingyi Du3

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Higher levels of Angiopoietin-like 4 (ANGPTL4) correlate with increased risks for ten different cancers. While not a universal causal factor, ANGPTL4 shows potential as a biomarker for cancer risk stratification.

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ANGPTL4Cohort studyHepatokinecancer risk

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Area of Science:

  • Biochemistry and Molecular Biology
  • Oncology
  • Epidemiology

Background:

  • Angiopoietin-like 4 (ANGPTL4) is a protein involved in metabolic and inflammatory processes.
  • ANGPTL4 has been linked to cancer development, but its association with human cancer risk is not well-established.

Purpose of the Study:

  • To investigate the relationship between circulating ANGPTL4 levels and the risk of developing various site-specific cancers in a large human cohort.
  • To evaluate the potential causal role of ANGPTL4 in cancer development using Mendelian randomization.

Main Methods:

  • Analysis of plasma ANGPTL4 levels in 35,716 cancer-free individuals from the UK Biobank.
  • Utilized multivariable Cox models and restricted cubic splines to assess associations with 24 incident cancers.
  • Employed bidirectional two-sample Mendelian randomization to explore causality.

Main Results:

  • Elevated ANGPTL4 levels were significantly associated with increased risk for ten cancers, including bladder, breast, colorectal, and liver cancer.
  • A dose-response relationship was observed, with higher ANGPTL4 quartiles corresponding to greater cancer risk.
  • Mendelian randomization did not support a causal role for ANGPTL4 in increasing overall cancer risk, but suggested ANGPTL4 may be elevated in liver cancer.

Conclusions:

  • Higher circulating ANGPTL4 is linked to an increased risk of multiple cancers, with variations observed based on sex and tissue type.
  • While not definitively causal, ANGPTL4 shows promise as a biomarker for identifying individuals at higher risk for cancer.
  • Further research may explore ANGPTL4's role in cancer prevention strategies and risk stratification.