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



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.


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.


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.


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

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Fig. 1: Hazard ratios (HRs) for total and site-specific cancer according to tertiles of C-reactive protein (CRP) by sex.

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We thank the participants and all the staff members in this study. We are indebted to the Aomori, Iwate, Akita, Ibaraki, Niigata, Osaka, Kochi, Nagasaki, and Okinawa Cancer Registries for providing their incidence data. The Japan Public Health Center-based Prospective Study members are listed at the after site:


This study was supported by the National Cancer Center Research and Development Fund (23-A-31 [toku], 26-A-2, and, 29-A-4), a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010), and the Practical Research for Innovative Cancer Control (JP16ck0106095 and JP19ck0106266) from the Japan Agency for Medical Research and Development. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the study.

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Authors and Affiliations




SS, RK and TY had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: SS, RK, TY and M Iwasaki. Acquisition, analysis, or interpretation of data: All authors. Statistical analysis: SS, RK and TY. Drafting of the manuscript: SS drafted the first manuscript with RK support. Critical revision of the manuscript for important intellectual content: All authors. Obtained funding: ST, M Iwasaki. Administrative, technical, or material support: TY, NS, ST and M Iwasaki. Supervision: TY, NS, M Inoue, ST and M Iwasaki.

Corresponding author

Correspondence to Ryoko Katagiri.

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Ethics approval and consent to participate

All precedures complied with the Helsinki Declaration. The comprehensive study protocol, including this study, was approved by the Institutional Review Board of the National Cancer Center, Tokyo, Japan (Approval No.2011-044). Before initiating this study, all living participants who had provided blood were contacted by mail and given the opportunity to opt-out of participation. Additionally, information on the study was posted on the website of our center to provide participants with the opportunity to opt-out at any time. Respondents who refused to participate were excluded from this study and their withdrawal of consent was documented.

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This manuscript does not contain any individual person’s data in any form, thus, consent for publication was not required.

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The authors declare no competing interests.

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Suzuki, S., Katagiri, R., Yamaji, T. et al. Association between C-reactive protein and risk of overall and 18 site-specific cancers in a Japanese case-cohort. Br J Cancer 126, 1481–1489 (2022).

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