Dataset Information

Genetically Predicted Circulating Level of C-Reactive Protein Is Not Associated With Prostate Cancer Risk.

ABSTRACT: Background:Inconsistent findings from observational studies have reported that C-reactive protein (CRP) is likely associated with risk of prostate cancer. Because conventional observational studies are susceptible to confounding and reverse causality, it remains unclear whether there is a causal relationship of CRP with risk of prostate cancer. Methods:In this study, we applied a two-sample Mendelian randomization (MR) approach to evaluate the potential causal association of circulating CRP levels with prostate cancer risk. Instrumental variables (IVs) and corresponding genetic association estimates for circulating CRP levels were obtained from a meta-analysis of genome-wide association studies (GWASs) including 204,402 participants of European descent. The genetic association estimates of these IVs with prostate cancer were obtained from a GWAS meta-analysis including 79,148 cases and 61,106 controls of European ancestry. The inverse-variance weighted (IVW) method was used as primary MR analyses, whereas in sensitivity analyses, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) test were used to assess the presence of pleiotropy. Odd ratio (OR) and 95% CI were calculated. Results:Overall, 58 single-nucleotide polymorphisms were used as instruments for circulating CRP levels. MR analysis suggested that genetically determined CRP levels were not associated with prostate cancer risk (OR 1.06, 95% CI 0.96 to 1.16) using the IVW method. Sensitivity analyses using alternative MR methods produced similar results (OR 1.00, 95% CI 0.93 to 1.08 for the weighted-median method; OR 1.02, 95% CI 0.95 to 1.08 for MR-PRESSO test). MR-Egger regression did not suggest evidence of directional pleiotropy (P = 0.25). Conclusion:Our study found that genetically predicted circulating CRP levels were not associated with prostate cancer risk, suggesting that CRP is unlikely to be a causal factor in the development of prostate cancer.

SUBMITTER: He C

PROVIDER: S-EPMC7591790 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetically Predicted Circulating Level of C-Reactive Protein Is Not Associated With Prostate Cancer Risk.

He Chiyu C Qian Yu Y Liu Bin B Yang Shaoxue S Ye Ding D Sun Xiaohui X Chen Tianhui T Mao Yingying Y

Frontiers in oncology 20201014

<h4>Background</h4>Inconsistent findings from observational studies have reported that C-reactive protein (CRP) is likely associated with risk of prostate cancer. Because conventional observational studies are susceptible to confounding and reverse causality, it remains unclear whether there is a causal relationship of CRP with risk of prostate cancer.<h4>Methods</h4>In this study, we applied a two-sample Mendelian randomization (MR) approach to evaluate the potential causal association of circu ...[more]

PMID: 33178578

Similar Datasets

Project description:IntroductionObservational studies have reported a relationship between iron status and the risk of prostate cancer. However, it remains uncertain whether the association is causal or due to confounding or reverse causality. To further clarify the underlying causal relationship, we conducted a Mendelian randomization (MR) analysis.MethodsWe selected three genetic variants (rs1800562, rs1799945, and rs855791) closely correlated with four iron status biomarkers (serum iron, log-transformed ferritin, transferrin saturation, and transferrin) as instrumental variables. Summary statistics for prostate cancer were obtained from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium including 79,148 cases and 61,106 controls of European ancestry. The inverse-variance weighted (IVW) method was conducted primarily to estimate the association of genetically predicted iron status and the risk of prostate cancer, supplemented with simple-median, weighted-median and maximum-likelihood methods as sensitivity analysis. MR-Egger regression was used to detect directional pleiotropy. We also conducted a meta-analysis of observational studies to assess the associations between iron status and the risk of prostate cancer.ResultsGenetically predicted increased iron status was associated with the decreased risk of prostate cancer, with odds ratio of 0.91 [95% confidence interval (CI): 0.84, 0.99; P = 0.035] for serum iron, 0.81 (95% CI: 0.65, 1.00; P = 0.046) for log- transformed ferritin, 0.94 (95% CI: 0.88, 0.99; P = 0.029) for transferrin saturation, and 1.15 (95% CI: 0.98, 1.35; P = 0.084) for transferrin (with higher transferrin levels representing lower systemic iron status), using the inverse-variance weighted method. Sensitivity analyses produced consistent associations, and MR-Egger regression indicated no potential pleiotropy. Our replication analysis based on FinnGen research project showed compatible results with our main analysis. Results from our meta-analysis similarly showed that serum ferritin [standardized mean difference (SMD): -1.25; 95% CI: -2.34, -0.16; P = 0.024] and transferrin saturation (SMD: -1.19; 95% CI: -2.34, -0.05; P = 0.042) were lower in patients with prostate cancer compared with that in controls.DiscussionOur study suggests a protective role of iron in the risk of prostate cancer, further investigations are required to clarify the underlying mechanisms.

Project description:BackgroundInflammation plays a pivotal role in the pathogenesis of cancer. Though previous studies have reported a link between several inflammatory biomarkers and risk of certain types of cancer, there is a lack of systematic investigation. Therefore, we aimed to assess the role of circulating cytokines on the risk of cancer using a two-sample Mendelian randomization (MR) approach.MethodWe used genetic variants associated with circulating levels of cytokines from a meta-analysis of genome-wide association studies (GWASs) of 8,293 Finns as instrumental variables. Summary level data of 20 site-specific cancer were obtained from the UK BioBank including up to 456,348 participants of European ancestry. We performed two-sample MR analyses using inverse-variance weighted (IVW) method as the main method, followed by weighted-median and likelihood-based methods as sensitivity analysis. Pleiotropic and outlier variants were assessed by MR-Egger regression and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test.Results224 genetic variants associated with 27 circulating cytokines achieving genome-wide significance (P<5×10-8) were used as IVs. After Bonferroni correction, genetically predicted high levels of interleukin-18 (IL-18) were associated with a decreased risk of acute myeloid leukemia (odds ratio (OR) per 1 standard deviation (SD) increase = 0.55, 95% confidence interval (CI):0.43-0.69, P=5.39×10-7), and circulating levels of IL-17 were associated with altered stomach cancer risk (OR per 1 SD increase = 0.15, 95% CI: 0.07-0.36, P=1.25×10-5) by IVW. Results were stable across sensitivity analyses, and MR-Egger regression did not suggest the presence of directional pleiotropy. Additionally, we found suggestive evidence for 48 cytokine-cancer associations including tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and cutaneous T-cell attracting chemokine (CTACK) with the risk of several types of cancer (9.26×10-5≤P<0.05).ConclusionsBy using a genetic epidemiological approach, our study systematically evaluated the role of circulating cytokines on the risk of cancer, and provided clues for potential therapeutic targets. However, the exact underlying biological mechanism warrants further investigation.

Dataset Information

Genetically Predicted Circulating Level of C-Reactive Protein Is Not Associated With Prostate Cancer Risk.

Publications

Genetically Predicted Circulating Level of C-Reactive Protein Is Not Associated With Prostate Cancer Risk.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets