C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis
Abstract Background Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | BMC Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12916-022-02506-x |
| _version_ | 1811265046421962752 |
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| author | Meng Zhu Zhimin Ma Xu Zhang Dong Hang Rong Yin Jifeng Feng Lin Xu Hongbing Shen |
| author_facet | Meng Zhu Zhimin Ma Xu Zhang Dong Hang Rong Yin Jifeng Feng Lin Xu Hongbing Shen |
| author_sort | Meng Zhu |
| collection | DOAJ |
| description | Abstract Background Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearity associations. Methods We analyzed 420,964 cancer-free participants from UK Biobank cohort. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the observed correlation of CRP with overall cancer and 21 site-specific cancer risks. Furthermore, we performed linear and non-linear Mendelian randomization analyses to explore the potential causal relation between them. Results During a median follow-up period of 7.1 years (interquartile range: 6.3, 7.7), 34,979 incident cancer cases were observed. Observational analyses showed higher CRP concentration was associated with increased risk of overall cancer (hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.02 per 1mg/L increase, P < 0.001). There was a non-linear association between CRP and overall cancer risk with inflection point at 3mg/L (false-discovery rate adjust (FDR-adjusted) P overall < 0.001 and FDR-adjusted P non-linear < 0.001). For site-specific cancer, we observed positive linear associations for cancers of esophagus and stomach (FDR-adjusted P overall < 0.050 and FDR-adjusted P non-linear > 0.050). In addition, we also observed three different patterns of non-linear associations, including “fast-to-low increase” (head and neck, colorectal, liver, lung, kidney cancer, and non-Hodgkin lymphoma), “increase-to-decrease” (breast cancer), and “decrease-to-platform” (chronic lymphocytic leukemia). Furthermore, the inflection points of non-linear association patterns were consistently at around 3mg/L. By contrast, there was no evidence for linear or non-linear associations between genetically predicted CRP and risks of overall cancer or site-specific cancers. Conclusions Our results indicated that CRP was a potential biomarker to assess risks of overall cancer and 12 site-specific cancers, while no association were observed for genetically-predicted CRP and cancer risks. |
| first_indexed | 2024-04-12T20:15:29Z |
| format | Article |
| id | doaj.art-fc69e04e2fa04eada43f3dc07e025c0c |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-12T20:15:29Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-fc69e04e2fa04eada43f3dc07e025c0c2022-12-22T03:18:08ZengBMCBMC Medicine1741-70152022-09-0120111310.1186/s12916-022-02506-xC-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysisMeng Zhu0Zhimin Ma1Xu Zhang2Dong Hang3Rong Yin4Jifeng Feng5Lin Xu6Hongbing Shen7Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical UniversityDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical UniversityDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical UniversityDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical UniversityDepartment of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical UniversityDepartment of Medical Oncology, Jiangsu Cancer Hospital &Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical UniversityDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical UniversityAbstract Background Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearity associations. Methods We analyzed 420,964 cancer-free participants from UK Biobank cohort. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the observed correlation of CRP with overall cancer and 21 site-specific cancer risks. Furthermore, we performed linear and non-linear Mendelian randomization analyses to explore the potential causal relation between them. Results During a median follow-up period of 7.1 years (interquartile range: 6.3, 7.7), 34,979 incident cancer cases were observed. Observational analyses showed higher CRP concentration was associated with increased risk of overall cancer (hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.02 per 1mg/L increase, P < 0.001). There was a non-linear association between CRP and overall cancer risk with inflection point at 3mg/L (false-discovery rate adjust (FDR-adjusted) P overall < 0.001 and FDR-adjusted P non-linear < 0.001). For site-specific cancer, we observed positive linear associations for cancers of esophagus and stomach (FDR-adjusted P overall < 0.050 and FDR-adjusted P non-linear > 0.050). In addition, we also observed three different patterns of non-linear associations, including “fast-to-low increase” (head and neck, colorectal, liver, lung, kidney cancer, and non-Hodgkin lymphoma), “increase-to-decrease” (breast cancer), and “decrease-to-platform” (chronic lymphocytic leukemia). Furthermore, the inflection points of non-linear association patterns were consistently at around 3mg/L. By contrast, there was no evidence for linear or non-linear associations between genetically predicted CRP and risks of overall cancer or site-specific cancers. Conclusions Our results indicated that CRP was a potential biomarker to assess risks of overall cancer and 12 site-specific cancers, while no association were observed for genetically-predicted CRP and cancer risks.https://doi.org/10.1186/s12916-022-02506-xC-reactive proteinCancer riskCohort studyMendelian randomization analysisNon-linear Mendelian randomization |
| spellingShingle | Meng Zhu Zhimin Ma Xu Zhang Dong Hang Rong Yin Jifeng Feng Lin Xu Hongbing Shen C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis BMC Medicine C-reactive protein Cancer risk Cohort study Mendelian randomization analysis Non-linear Mendelian randomization |
| title | C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis |
| title_full | C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis |
| title_fullStr | C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis |
| title_full_unstemmed | C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis |
| title_short | C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis |
| title_sort | c reactive protein and cancer risk a pan cancer study of prospective cohort and mendelian randomization analysis |
| topic | C-reactive protein Cancer risk Cohort study Mendelian randomization analysis Non-linear Mendelian randomization |
| url | https://doi.org/10.1186/s12916-022-02506-x |
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