Dataset Information

Genetically lowered concentrations of circulating sRAGE might cause an increased risk of cancer: Meta-analysis using Mendelian randomization.

ABSTRACT: To undertake a systematic meta-analysis of all variants in the gene encoding receptor for advanced glycation end products (RAGE) to summarize their associations with cancer risk and changes in the levels of circulating soluble RAGE (sRAGE), with the aim of determining possible causality between circulating sRAGE and cancer risk.Articles written in English were retrieved from MEDLINE® and EMBASE® databases. Two researchers independently identified eligible articles and extracted the data (analysed using STATA® software version 12.0).Fifteen articles qualified for inclusion in the meta-analysis of the RAGE-cancer association and three examined the RAGE-sRAGE relationship. The 82Ser/82Ser genotype was significantly associated with overall cancer risk compared with the 82Gly/Gly genotype (odds ratio 1.75, 95% confidence interval [CI] 1.46, 2.10). Carriers of the 82Ser/82Ser genotype had significantly reduced circulating sRAGE concentrations compared with the 82Gly/82Gly genotype. Mendelian randomization analysis demonstrated that a reduction of 100, 200 and 300?pg/ml in circulating sRAGE concentrations was associated with a 1.11-fold (95% CI 1.06, 1.25), 1.24-fold (95% CI 1.11, 1.57) and 1.38-fold (95% CI 1.18, 1.96) increased risk of developing cancer, respectively.Genetically lowered concentrations of circulating sRAGE might cause an increased risk of cancer.

SUBMITTER: Huang Q

PROVIDER: S-EPMC5580070 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Genetically lowered concentrations of circulating sRAGE might cause an increased risk of cancer: Meta-analysis using Mendelian randomization.

Huang Qingxian Q Mi Jia J Wang Xizhen X Liu Fang F Wang Dan D Yan Dong D Wang Bin B Zhang Shuping S Tian Geng G

The Journal of international medical research 20160208 2

<h4>Objectives</h4>To undertake a systematic meta-analysis of all variants in the gene encoding receptor for advanced glycation end products (RAGE) to summarize their associations with cancer risk and changes in the levels of circulating soluble RAGE (sRAGE), with the aim of determining possible causality between circulating sRAGE and cancer risk.<h4>Methods</h4>Articles written in English were retrieved from MEDLINE® and EMBASE® databases. Two researchers independently identified eligible artic ...[more]

PMID: 26857858

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Project description:BackgroundCoronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which since 2019 has caused over 5 million deaths to date. The pathogenicity of the virus is highly variable ranging from asymptomatic to fatal. Evidence from experimental and observational studies suggests that circulating micronutrients may affect COVID-19 outcomes.ObjectivesTo complement and inform observational studies, we investigated the associations of genetically predicted concentrations of 12 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, vitamin D, and zinc) with SARS-CoV-2 infection risk and COVID-19 severity using Mendelian randomization (MR).MethodsTwo-sample MR was conducted using 87,870 individuals of European descent with a COVID-19 diagnosis and 2,210,804 controls from the COVID-19 host genetics initiative. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.ResultsCompared to the general population, nominally significant associations were noted for higher genetically predicted vitamin B-6 (Odds ratio per standard deviation [OR SD]: 1.06; 95% confidence interval [CI]: 1.00, 1.13; p-value = 0.036) and lower magnesium concentrations (OR SD: 0.33; 95%CI: 0.11, 0.96; P = 0.042) with COVID-19 infection risk. However, the association for magnesium was not consistent in some sensitivity analyses, and sensitivity analyses could not be performed for vitamin B-6 as only two genetic instruments were available. Genetically predicted levels of calcium, folate, β-carotene, copper, iron, vitamin B-12, vitamin D, selenium, phosphorus, or zinc were not associated with the outcomes from COVID-19 disease.ConclusionThese results, though based only on genetically predicated circulating micronutrient concentrations, provide scant evidence for possible associations of micronutrients with COVID-19 outcomes.

Project description:BackgroundThe literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.ObjectivesTo complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).MethodsTwo-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.ResultsNominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.ConclusionsThese results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.

Dataset Information

Genetically lowered concentrations of circulating sRAGE might cause an increased risk of cancer: Meta-analysis using Mendelian randomization.

Publications

Genetically lowered concentrations of circulating sRAGE might cause an increased risk of cancer: Meta-analysis using Mendelian randomization.

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