Evidence map›Paper›PMID 29694444›Full record

ArticlePloS one2018

One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status.

Robin Myte, Björn Gylling, Jenny Häggström, Jörn Schneede, Anna Löfgren-Burström, Jeroen R Huyghe, Göran Hallmans, Klaus Meyer, Ingegerd Johansson, Per Magne Ueland and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Robin MyteDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.ORCID 0000-0002-2974-2003
Björn GyllingDepartment of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Jenny HäggströmDepartment of Statistics, Umeå School of Business and Economics, Umeå University, Umeå, Sweden.
Jörn SchneedeDepartment of Clinical Pharmacology, Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden.
Anna Löfgren-BurströmDepartment of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Jeroen R HuygheFred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Göran HallmansDepartment of Biobank Research, Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Klaus MeyerBevital AS, Bergen, Norway.
Ingegerd JohanssonDepartment of Odontology, Cariology, Umeå University, Umeå, Sweden.
Per Magne UelandDepartment of Clinical Science, University of Bergen, Bergen, Norway.
Richard PalmqvistDepartment of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Bethany Van GuelpenDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Umeå University · SEBevital (Norway) · NOFred Hutch Cancer Center · USHaukeland University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Disturbances in one-carbon metabolism, intracellular reactions involved in nucleotide synthesis and methylation, likely increase the risk of colorectal cancer (CRC). However, results have been inconsistent. To explore whether this inconsistency could be explained by intertumoral heterogeneity, we evaluated a comprehensive panel of one-carbon metabolism biomarkers and some single nucleotide polymorphisms (SNPs) in relation to the risk of molecular subtypes of CRC defined by mutations in the KRAS and BRAF oncogenes. This nested case-control study included 488 CRC cases and 947 matched controls from two population-based cohorts in the Northern Sweden Health and Disease Study. We analyzed 14 biomarkers and 17 SNPs in prediagnostic blood and determined KRAS and BRAF mutation status in tumor tissue. In a multivariate network analysis, no variable displayed a strong association with the risk of specific CRC subtypes. A non-synonymous SNP in the CTH gene, rs1021737, had a stronger association compared with other variables. In subsequent univariate analyses, participants with variant rs1021737 genotype had a decreased risk of KRAS-mutated CRC (OR per allele = 0.72, 95% CI = 0.50, 1.05), and an increased risk of BRAF-mutated CRC (OR per allele = 1.56, 95% CI = 1.07, 2.30), with weak evidence for heterogeneity (Pheterogeneity = 0.01). This subtype-specific SNP association was not replicated in a case-case analysis of 533 CRC cases from The Cancer Genome Atlas (P = 0.85). In conclusion, we found no support for clear subtype-specific roles of one-carbon metabolism biomarkers and SNPs in CRC development, making differences in CRC molecular subtype distributions an unlikely explanation for the varying results on the role of one-carbon metabolism in CRC development across previous studies. Further investigation of the CTH gene in colorectal carcinogenesis with regards to KRAS and BRAF mutations or other molecular characteristics of the tumor may be warranted.

Indexed as

Polymorphism, Single NucleotideBiomarkers, TumorCarbonCase-Control StudiesColorectal NeoplasmsCystathionine gamma-LyaseFemaleGene Regulatory NetworksGenetic Association StudiesHumansMaleMiddle AgedProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)SwedenBiomarkers, TumorBRAF protein, humanCarbonCystathionine gamma-LyaseKRAS protein, humanProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)

Identifiers

PMID29694444
PMCPMC5919009
OpenAlexW2799658862

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.