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Plasma C-reactive protein, genetic risk score, and risk of common cancers in the Atherosclerosis Risk in Communities study

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Abstract

Purpose

Many studies, including the Atherosclerosis Risk in Communities (ARIC) cohort, reported a positive association between plasma C-reactive protein (CRP)—a biomarker of low-grade chronic inflammation—and colorectal cancer risk, although it is unclear whether the association is causal. Our aims were to assess the associations of a CRP genetic risk score (CRP-GRS) created from single-nucleotide polymorphisms (SNPs) with colorectal cancer risk, as well as examine plasma CRP and CRP-GRS in relation to common cancers in the ARIC cohort.

Methods

Cox proportional hazards models were used to prospectively estimate hazard ratios (HRs) and 95 % confidence interval (95 % CI) of total, colorectal, lung, prostate, and breast cancers in relation to: (1) CRP-GRS among 8,657 Whites followed in 1987–2006 and (2) log-transformed plasma CRP among 7,603 Whites followed in 1996–2006. A weighted CRP-GRS was comprised of 20 CRP-related SNPs located in/near CRP, APOC1, HNF1A, LEPR, and 16 other genes that were identified in genome-wide association studies.

Results

After multivariable adjustment, one standard deviation increment of the CRP-GRS was associated with colorectal cancer risk (HR 1.19; 95 % CI 1.03–1.37), but not with any other cancer. One unit of log-transformed plasma CRP was associated with the risk of total, colorectal, lung, and breast cancers: HRs (95 % CIs) were 1.08 (1.01–1.15), 1.24 (1.01–1.51), 1.29 (1.08–1.54), and 1.27 (1.07–1.51), respectively. HRs remained elevated, although lost statistical significance for all but breast cancer, after excluding subjects with <2 years of follow-up.

Conclusions

The study corroborates a causative role of chronic low-grade inflammation in colorectal carcinogenesis.

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Acknowledgments

The Atherosclerosis Risk in Communities study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. Studies on cancer in ARIC are also supported by the National Cancer Institute (U01 CA164975-01). Cancer incidence data have been provided by Maryland Cancer Registry, Center of Cancer Surveillance and Control, Department of Health and Mental Hygiene, 201 W. Preston Street, Room 400, Baltimore, MD 21201. We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries (NPCR) of the Centers for disease control and Prevention (CDC) for the funds that helped support the availability of the cancer registry data. A.E. Prizment was supported as a postdoctoral fellow by training Grant T32CA132670 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The authors thank the staff and participants of the ARIC study for their important contributions.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 2nd Street South, Suite 300, Minneapolis, MN, 55455, USA

    Anna E. Prizment, Aaron R. Folsom, Jill Dreyfus, Kristin E. Anderson & James S. Pankow

  2. University of Minnesota Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Aaron R. Folsom & Kristin E. Anderson

  3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Kala Visvanathan, Corinne E. Joshu & Elizabeth A. Platz

  4. James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Elizabeth A. Platz

  5. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Elizabeth A. Platz

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  1. Anna E. Prizment
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  2. Aaron R. Folsom
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  3. Jill Dreyfus
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Correspondence to Anna E. Prizment.

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Prizment, A.E., Folsom, A.R., Dreyfus, J. et al. Plasma C-reactive protein, genetic risk score, and risk of common cancers in the Atherosclerosis Risk in Communities study. Cancer Causes Control 24, 2077–2087 (2013). https://doi.org/10.1007/s10552-013-0285-y

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