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Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study.

ABSTRACT: Genetic variants have been associated with the risk of developing glioma, but functional mechanisms on disease phenotypic traits remain to be investigated. One phenotypic trait of glioblastoma is the mutation and amplification of the epidermal growth factor receptor (EGFR) gene. We investigated associations between pre-diagnostic serum protein concentrations of EGFR and ErbB2, both members of the EGFR family, and future risk of glioma. Further, we studied if EGFR glioma risk variants were associated with EGFR and ErbB2 serum levels. We assessed the associations between genetic glioma risk variants and serum concentrations of EGFR and ErbB2, as measured in pre-diagnostic cohort serum samples of 593 glioma patients and 590 matched cancer-free controls. High serum EGFR and ErbB2 levels were associated with risk of developing glioblastoma (P?=?0.008; OR?=?1.58, 95 % CI?=?1.13-2.22 and P?=?0.017, OR?=?1.63, 95 % CI?=?1.09-2.44, respectively). High serum ErbB2 concentration was also associated with glioma risk overall (P?=?0.049; OR?=?1.39, 95 % CI?=?1.00-1.93). Glioma risk variants were not associated with high serum protein abundance. In contrast, the EGFR risk variant rs4947986 (T) was correlated with decreased EGFR serum levels (study cohort P?=?0.024 and controls P?=?0.009). To our knowledge, this is the first study showing an association of EGFR and ErbB2 serum levels with glioma more than a decade before diagnosis, indicating that EGFR and ErbB2 serum proteins are important in early gliomagenesis. However, we did not find evidence that glioma risk variants were associated with high pre-diagnostic serum concentrations of EGFR and ErbB2.

SUBMITTER: Spath F

PROVIDER: S-EPMC4999462 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study.

Späth Florentin F Andersson Ulrika U Dahlin Anna M AM Langseth Hilde H Hovig Eivind E Johannesen Tom Børge TB Grankvist Kjell K Björkblom Benny B Wibom Carl C Melin Beatrice B

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20160223 8

Genetic variants have been associated with the risk of developing glioma, but functional mechanisms on disease phenotypic traits remain to be investigated. One phenotypic trait of glioblastoma is the mutation and amplification of the epidermal growth factor receptor (EGFR) gene. We investigated associations between pre-diagnostic serum protein concentrations of EGFR and ErbB2, both members of the EGFR family, and future risk of glioma. Further, we studied if EGFR glioma risk variants were associ ...[more]

PMID: 26906551

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Project description:BackgroundSerum choline levels were associated with multiple chronic diseases. However, the association between serum choline and all-cause mortality in Chinese adults with hypertension remains unclear. The purpose of this study is to explore the association between serum choline concentrations and all-cause mortality risk in Chinese adults with hypertension, a high-risk population.MethodsA nested, case-control study was conducted that included 279 patients with all-cause death, and 279 matched, living controls, derived from the China Stroke Primary Prevention Trial (CSPPT). Baseline serum choline concentrations were measured by liquid chromatography with tandem quadrupole mass spectrometry (LC-MS/MS). Multivariate logistic regression analysis was used to assess the association of serum choline levels and all-cause mortality risk, with adjustment of pertinent covariables, including folic acid and homocysteine.ResultsThe median age of all participants was 64.13 years [interquartile range (IQR), 57.33-70.59 years]. The median serum choline concentration for cases (9.51 μg/mL) was higher than that in controls (7.80 μg/mL) (P = 0.009). When serum choline concentration was assessed as a continuous variable (per SD increased), there was a positive relation between serum choline levels and all-cause mortality risk [odds ratios (OR), 1.29; 95% confidence intervals (95%CI), 1.06-1.57; P = 0.010]. There was an increased all-cause mortality risk for participants in quartiles 2-4 (≥ 4.00 μg/mL; OR, 1.79; 95%CI, 1.15-2.78 compared with quartile 1 (< 4.00 μg/mL). In addition, non-drinking was found to promote the incidence of all-cause mortality for those with high choline concentrations.ConclusionsHigh serum choline concentrations were associated with increased all-cause mortality risk among Chinese adults with hypertension, compared to lower choline concentrations. Trial registration clinicaltrials.gov Identifier: NCT007948885; UTL: https://clinicaltrials.gov/ct2/show/NCT00794885?term=NCT00794885&draw=2&rank=1.

Project description:ObjectiveTo examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations.DesignNested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries.Participants1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controlsMain outcome measuresCirculating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders.Results25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); >or=100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation.ConclusionsThe results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

Dataset Information

Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study.

Publications

Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study.

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