Association between C-reactive protein and risk of overall and 18 site-specific cancers in a Japanese case-cohort

Br J Cancer. 2022 Jun;126(10):1481-1489. doi: 10.1038/s41416-022-01715-8. Epub 2022 Feb 10.


Background: Evidence of the association between chronic low-grade inflammation, as reflected by C-reactive protein (CRP) measurements, and cancer risk is equivocal. Specifically, few studies have examined this in uncommon cancers and Asian populations.

Methods: We utilised a case-cohort design consisting of multi-types of cancer (N = 3608), and a random subcohort (N = 4432) in a Japanese large population-based study, with a median follow-up time of 15.6 years, and measured baseline plasma CRP using high sensitivity assay. The hazard ratios (HRs) were estimated using weighted Cox proportional hazards methods.

Results: The multivariable-adjusted HR (95% confidence interval) for the top quartile of CRP was 1.28 (1.11‒1.48) (Ptrend < 0.001) for overall cancer compared to the bottom quartile of CRP. Among site-specific cancers, higher CRP levels were associated with an increased risk of colorectal, lung, breast, biliary tract, and kidney cancer, and leukaemia. These positive associations remained among participants after >3 years' follow-up. Furthermore, subgroup analyses for overall cancer robustly showed a positive association with CRP levels, regardless of sex and obesity.

Conclusion: Our consistent findings suggested that chronic low-grade inflammation measured by CRP is associated with the risk of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Reactive Protein* / metabolism
  • Female
  • Humans
  • Inflammation / complications
  • Japan / epidemiology
  • Kidney Neoplasms*
  • Male
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors


  • C-Reactive Protein