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Mendelian randomization analysis of C-reactive protein on colorectal cancer risk
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2019 (English)In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 48, no 3, p. 767-780Article in journal (Refereed) Published
Abstract [en]

Background: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach.

Methods: Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk.

Results: Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors.

Conclusions: In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.

Place, publisher, year, edition, pages
2019. Vol. 48, no 3, p. 767-780
Keywords [en]
C-reactive protein, colorectal cancer, Mendelian randomization, epidemiology
National Category
Occupational Health and Environmental Health Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:uu:diva-368142DOI: 10.1093/ije/dyy244ISI: 000486642400016PubMedID: 30476131OAI: oai:DiVA.org:uu-368142DiVA, id: diva2:1267944
Funder
NIH (National Institute of Health)German Research Foundation (DFG)Swedish Research CouncilSwedish Cancer SocietyAvailable from: 2018-12-04 Created: 2018-12-04 Last updated: 2019-10-30Bibliographically approved

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Wolk, Alicja

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