One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status.
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 ev...
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ftdoajarticles:oai:doaj.org/article:f02b462f5ca24b7a8d5f6aeeefe5861e 2023-05-15T17:45:06+02:00 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 Richard Palmqvist Bethany Van Guelpen 2018-01-01T00:00:00Z https://doi.org/10.1371/journal.pone.0196233 https://doaj.org/article/f02b462f5ca24b7a8d5f6aeeefe5861e EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5919009?pdf=render https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0196233 https://doaj.org/article/f02b462f5ca24b7a8d5f6aeeefe5861e PLoS ONE, Vol 13, Iss 4, p e0196233 (2018) Medicine R Science Q article 2018 ftdoajarticles https://doi.org/10.1371/journal.pone.0196233 2022-12-31T14:59:14Z 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. Article in Journal/Newspaper Northern Sweden Directory of Open Access Journals: DOAJ Articles PLOS ONE 13 4 e0196233 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Robin Myte Björn Gylling Jenny Häggström Jörn Schneede Anna Löfgren-Burström Jeroen R Huyghe Göran Hallmans Klaus Meyer Ingegerd Johansson Per Magne Ueland Richard Palmqvist Bethany Van Guelpen One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status. |
topic_facet |
Medicine R Science Q |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Robin Myte Björn Gylling Jenny Häggström Jörn Schneede Anna Löfgren-Burström Jeroen R Huyghe Göran Hallmans Klaus Meyer Ingegerd Johansson Per Magne Ueland Richard Palmqvist Bethany Van Guelpen |
author_facet |
Robin Myte Björn Gylling Jenny Häggström Jörn Schneede Anna Löfgren-Burström Jeroen R Huyghe Göran Hallmans Klaus Meyer Ingegerd Johansson Per Magne Ueland Richard Palmqvist Bethany Van Guelpen |
author_sort |
Robin Myte |
title |
One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status. |
title_short |
One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status. |
title_full |
One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status. |
title_fullStr |
One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status. |
title_full_unstemmed |
One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status. |
title_sort |
one-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by kras and braf mutation status. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pone.0196233 https://doaj.org/article/f02b462f5ca24b7a8d5f6aeeefe5861e |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_source |
PLoS ONE, Vol 13, Iss 4, p e0196233 (2018) |
op_relation |
http://europepmc.org/articles/PMC5919009?pdf=render https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0196233 https://doaj.org/article/f02b462f5ca24b7a8d5f6aeeefe5861e |
op_doi |
https://doi.org/10.1371/journal.pone.0196233 |
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PLOS ONE |
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13 |
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4 |
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e0196233 |
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