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Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes
BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease that can develop via 3 major pathways: conventional, serrated, and alternate. We aimed to examine whether the risk factor profiles differ according to pathway-related molecular subtypes. METHODS: We examined the association of 24 risk fa...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791624/ https://www.ncbi.nlm.nih.gov/pubmed/33442661 http://dx.doi.org/10.1093/jncics/pkaa089 |
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author | Wang, Liang He, Xiaosheng Ugai, Tomotaka Haruki, Koichiro Lo, Chun-Han Hang, Dong Akimoto, Naohiko Fujiyoshi, Kenji Wang, Molin Fuchs, Charles S Meyerhardt, Jeffrey A Zhang, Xuehong Wu, Kana Chan, Andrew T Giovannucci, Edward L Ogino, Shuji Song, Mingyang |
author_facet | Wang, Liang He, Xiaosheng Ugai, Tomotaka Haruki, Koichiro Lo, Chun-Han Hang, Dong Akimoto, Naohiko Fujiyoshi, Kenji Wang, Molin Fuchs, Charles S Meyerhardt, Jeffrey A Zhang, Xuehong Wu, Kana Chan, Andrew T Giovannucci, Edward L Ogino, Shuji Song, Mingyang |
author_sort | Wang, Liang |
collection | PubMed |
description | BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease that can develop via 3 major pathways: conventional, serrated, and alternate. We aimed to examine whether the risk factor profiles differ according to pathway-related molecular subtypes. METHODS: We examined the association of 24 risk factors with 4 CRC molecular subtypes based on a combinatorial status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations by collecting data from 2 large US cohorts. We used inverse probability weighted duplication-method Cox proportional hazards regression to evaluate differential associations across subtypes. RESULTS: We documented 1175 CRC patients with molecular subtype data: subtype 1 (n = 498; conventional pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-wild-type), subtype 2 (n = 138; serrated pathway; any MSI status, CIMP-high, BRAF-mutated, KRAS-wild-type), subtype 3 (n = 367; alternate pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-mutated), and subtype 4 (n = 172; other marker combinations). Statistically significant heterogeneity in associations with CRC subtypes was found for age, sex, and smoking, with a higher hazard ratio (HR) observed for the subtype 2 (HR per 10 years of age = 2.64, 95% CI = 2.13 to 3.26; HR for female = 2.65, 95% CI = 1.60 to 4.39; HR per 20-pack-year of smoking = 1.29, 95% CI = 1.14 to 1.45) than other CRC subtypes (all P(heterogeneity) < .005). A stronger association was found for adiposity measures with subtype 1 CRC in men and subtype 3 CRC in women and for several dietary factors with subtype 1 CRC, although these differences did not achieve statistical significance at α level of .005. CONCLUSIONS: Risk factor profiles may differ for CRC arising from different molecular pathways. |
format | Online Article Text |
id | pubmed-7791624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77916242021-01-12 Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes Wang, Liang He, Xiaosheng Ugai, Tomotaka Haruki, Koichiro Lo, Chun-Han Hang, Dong Akimoto, Naohiko Fujiyoshi, Kenji Wang, Molin Fuchs, Charles S Meyerhardt, Jeffrey A Zhang, Xuehong Wu, Kana Chan, Andrew T Giovannucci, Edward L Ogino, Shuji Song, Mingyang JNCI Cancer Spectr Article BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease that can develop via 3 major pathways: conventional, serrated, and alternate. We aimed to examine whether the risk factor profiles differ according to pathway-related molecular subtypes. METHODS: We examined the association of 24 risk factors with 4 CRC molecular subtypes based on a combinatorial status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations by collecting data from 2 large US cohorts. We used inverse probability weighted duplication-method Cox proportional hazards regression to evaluate differential associations across subtypes. RESULTS: We documented 1175 CRC patients with molecular subtype data: subtype 1 (n = 498; conventional pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-wild-type), subtype 2 (n = 138; serrated pathway; any MSI status, CIMP-high, BRAF-mutated, KRAS-wild-type), subtype 3 (n = 367; alternate pathway; non-MSI-high, CIMP-low or negative, BRAF-wild-type, KRAS-mutated), and subtype 4 (n = 172; other marker combinations). Statistically significant heterogeneity in associations with CRC subtypes was found for age, sex, and smoking, with a higher hazard ratio (HR) observed for the subtype 2 (HR per 10 years of age = 2.64, 95% CI = 2.13 to 3.26; HR for female = 2.65, 95% CI = 1.60 to 4.39; HR per 20-pack-year of smoking = 1.29, 95% CI = 1.14 to 1.45) than other CRC subtypes (all P(heterogeneity) < .005). A stronger association was found for adiposity measures with subtype 1 CRC in men and subtype 3 CRC in women and for several dietary factors with subtype 1 CRC, although these differences did not achieve statistical significance at α level of .005. CONCLUSIONS: Risk factor profiles may differ for CRC arising from different molecular pathways. Oxford University Press 2020-10-07 /pmc/articles/PMC7791624/ /pubmed/33442661 http://dx.doi.org/10.1093/jncics/pkaa089 Text en © The Author(s) 2020. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Wang, Liang He, Xiaosheng Ugai, Tomotaka Haruki, Koichiro Lo, Chun-Han Hang, Dong Akimoto, Naohiko Fujiyoshi, Kenji Wang, Molin Fuchs, Charles S Meyerhardt, Jeffrey A Zhang, Xuehong Wu, Kana Chan, Andrew T Giovannucci, Edward L Ogino, Shuji Song, Mingyang Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes |
title | Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes |
title_full | Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes |
title_fullStr | Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes |
title_full_unstemmed | Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes |
title_short | Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes |
title_sort | risk factors and incidence of colorectal cancer according to major molecular subtypes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791624/ https://www.ncbi.nlm.nih.gov/pubmed/33442661 http://dx.doi.org/10.1093/jncics/pkaa089 |
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