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Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways

BACKGROUND: Smoking and alcohol increase risk for colorectal malignancies. However, colorectal cancer (CRC) is a heterogenic disease and associations with the molecular pathological pathways are unclear. METHODS: This population-based case–control study includes 2444 cases with first-diagnosis CRC a...

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Autores principales: Amitay, Efrat L., Carr, Prudence R., Jansen, Lina, Roth, Wilfried, Alwers, Elizabeth, Herpel, Esther, Kloor, Matthias, Bläker, Hendrik, Chang-Claude, Jenny, Brenner, Hermann, Hoffmeister, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250912/
https://www.ncbi.nlm.nih.gov/pubmed/32225169
http://dx.doi.org/10.1038/s41416-020-0803-0
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author Amitay, Efrat L.
Carr, Prudence R.
Jansen, Lina
Roth, Wilfried
Alwers, Elizabeth
Herpel, Esther
Kloor, Matthias
Bläker, Hendrik
Chang-Claude, Jenny
Brenner, Hermann
Hoffmeister, Michael
author_facet Amitay, Efrat L.
Carr, Prudence R.
Jansen, Lina
Roth, Wilfried
Alwers, Elizabeth
Herpel, Esther
Kloor, Matthias
Bläker, Hendrik
Chang-Claude, Jenny
Brenner, Hermann
Hoffmeister, Michael
author_sort Amitay, Efrat L.
collection PubMed
description BACKGROUND: Smoking and alcohol increase risk for colorectal malignancies. However, colorectal cancer (CRC) is a heterogenic disease and associations with the molecular pathological pathways are unclear. METHODS: This population-based case–control study includes 2444 cases with first-diagnosis CRC and 2475 controls. Tumour tissue was analysed for MSI (microsatellite instability), CIMP (CpG island methylator phenotype), BRAF (B-Raf proto-oncogene serine/threonine kinase gene) and KRAS (Kirsten rat sarcoma viral oncogene homologue gene) mutations. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for associations between alcohol and smoking and CRC molecular subtypes and pathways. RESULTS: Current smoking showed higher ORs for MSI-high (OR = 2.79, 95% CI: 1.86–4.18) compared to MSS (OR = 1.41, 1.14–1.75, p-heterogeneity (p-het) = 0.001), BRAF-mutated (mut) (OR = 2.40, 1.41–4.07) compared to BRAF-wild type (wt) (OR = 1.52, 1.24–1.88, p-het = 0.074), KRAS-wt (OR = 1.70, 1.36–2.13) compared to KRAS-mut (OR = 1.26, 0.95–1.68, p-het = 0.039) and CIMP-high (OR = 2.01, 1.40–2.88) compared to CIMP-low/negative CRC (OR = 1.50, 1.22–1.85, p-het=0.101). Current smoking seemed more strongly associated with sessile serrated pathway (CIMP-high + BRAF-mut; OR = 2.39, 1.27–4.52) than with traditional pathway CRC (MSS + CIMP-low/negative + BRAF-wt; OR = 1.50, 1.16–1.94) and no association was observed with alternate pathway CRC (MSS + CIMP-low/negative + KRAS-wt; OR = 1.08, 0.77–1.43). No heterogeneity was observed in alcohol consumption association by molecular subtypes. CONCLUSIONS: In this large case–control study, smoking was more strongly associated with MSI-high and KRAS-wt CRC and with cases showing features of the sessile serrated pathway. Association patterns were less clear for alcohol consumption.
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spelling pubmed-72509122020-06-04 Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways Amitay, Efrat L. Carr, Prudence R. Jansen, Lina Roth, Wilfried Alwers, Elizabeth Herpel, Esther Kloor, Matthias Bläker, Hendrik Chang-Claude, Jenny Brenner, Hermann Hoffmeister, Michael Br J Cancer Article BACKGROUND: Smoking and alcohol increase risk for colorectal malignancies. However, colorectal cancer (CRC) is a heterogenic disease and associations with the molecular pathological pathways are unclear. METHODS: This population-based case–control study includes 2444 cases with first-diagnosis CRC and 2475 controls. Tumour tissue was analysed for MSI (microsatellite instability), CIMP (CpG island methylator phenotype), BRAF (B-Raf proto-oncogene serine/threonine kinase gene) and KRAS (Kirsten rat sarcoma viral oncogene homologue gene) mutations. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for associations between alcohol and smoking and CRC molecular subtypes and pathways. RESULTS: Current smoking showed higher ORs for MSI-high (OR = 2.79, 95% CI: 1.86–4.18) compared to MSS (OR = 1.41, 1.14–1.75, p-heterogeneity (p-het) = 0.001), BRAF-mutated (mut) (OR = 2.40, 1.41–4.07) compared to BRAF-wild type (wt) (OR = 1.52, 1.24–1.88, p-het = 0.074), KRAS-wt (OR = 1.70, 1.36–2.13) compared to KRAS-mut (OR = 1.26, 0.95–1.68, p-het = 0.039) and CIMP-high (OR = 2.01, 1.40–2.88) compared to CIMP-low/negative CRC (OR = 1.50, 1.22–1.85, p-het=0.101). Current smoking seemed more strongly associated with sessile serrated pathway (CIMP-high + BRAF-mut; OR = 2.39, 1.27–4.52) than with traditional pathway CRC (MSS + CIMP-low/negative + BRAF-wt; OR = 1.50, 1.16–1.94) and no association was observed with alternate pathway CRC (MSS + CIMP-low/negative + KRAS-wt; OR = 1.08, 0.77–1.43). No heterogeneity was observed in alcohol consumption association by molecular subtypes. CONCLUSIONS: In this large case–control study, smoking was more strongly associated with MSI-high and KRAS-wt CRC and with cases showing features of the sessile serrated pathway. Association patterns were less clear for alcohol consumption. Nature Publishing Group UK 2020-03-30 2020-05-26 /pmc/articles/PMC7250912/ /pubmed/32225169 http://dx.doi.org/10.1038/s41416-020-0803-0 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Amitay, Efrat L.
Carr, Prudence R.
Jansen, Lina
Roth, Wilfried
Alwers, Elizabeth
Herpel, Esther
Kloor, Matthias
Bläker, Hendrik
Chang-Claude, Jenny
Brenner, Hermann
Hoffmeister, Michael
Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways
title Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways
title_full Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways
title_fullStr Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways
title_full_unstemmed Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways
title_short Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways
title_sort smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250912/
https://www.ncbi.nlm.nih.gov/pubmed/32225169
http://dx.doi.org/10.1038/s41416-020-0803-0
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