Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status
Factors related to energy metabolism and the metabolic syndrome, such as higher body mass index (BMI), blood glucose, or blood lipids, and blood pressure, are associated with an increased risk of colorectal cancer (CRC). However, CRC is a heterogeneous disease, developing through distinct pathways w...
Published in: | International Journal of Cancer |
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crwiley:10.1002/ijc.32104 2024-06-02T08:12:12+00:00 Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status Myte, Robin Gylling, Björn Häggström, Jenny Häggström, Christel Zingmark, Carl Löfgren Burström, Anna Palmqvist, Richard Van Guelpen, Bethany Cancer Research Foundation in Northern Sweden Cancerfonden Medicinska fakulteten, Umeå Universitet 2019 http://dx.doi.org/10.1002/ijc.32104 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fijc.32104 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.32104 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ijc.32104 en eng Wiley http://creativecommons.org/licenses/by-nc/4.0/ International Journal of Cancer volume 145, issue 2, page 327-337 ISSN 0020-7136 1097-0215 journal-article 2019 crwiley https://doi.org/10.1002/ijc.32104 2024-05-03T10:59:12Z Factors related to energy metabolism and the metabolic syndrome, such as higher body mass index (BMI), blood glucose, or blood lipids, and blood pressure, are associated with an increased risk of colorectal cancer (CRC). However, CRC is a heterogeneous disease, developing through distinct pathways with differences in molecular characteristics and prognosis, and possibly also in risk factors. For subtypes defined by KRAS and BRAF mutation status, BMI is the only metabolic factor previously studied, with inconsistent findings. We investigated whether associations between BMI, blood glucose, blood lipids, and blood pressure and CRC risk differed by tumor KRAS and BRAF mutation status in 117,687 participants from two population‐based cohorts within the Northern Sweden Health and Disease Study (NSHDS). Hazard ratios (HRs) for overall CRC and CRC subtypes by metabolic factors were estimated with Cox proportional hazards regression, using multiple imputation to handle missing exposure and tumor data. During a median follow‐up of 15.6 years, we acquired 1,250 prospective CRC cases, of which 766 cases had complete baseline and molecular tumor data. Consistent with previous evidence, higher BMI, total cholesterol, triglyceride levels, and blood pressure were associated with an increased risk of overall CRC (HRs per 1 standard deviation increase: 1.07 to 1.12). These associations were similar regardless of CRC subtype by KRAS and BRAF mutation status (all p heterogeneity > 0.05). The same was true for subtypes based on microsatellite instability status. Poor metabolic health may therefore be a universal mechanism for colorectal cancer, acting across multiple developmental pathways. Article in Journal/Newspaper Northern Sweden Wiley Online Library International Journal of Cancer 145 2 327 337 |
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English |
description |
Factors related to energy metabolism and the metabolic syndrome, such as higher body mass index (BMI), blood glucose, or blood lipids, and blood pressure, are associated with an increased risk of colorectal cancer (CRC). However, CRC is a heterogeneous disease, developing through distinct pathways with differences in molecular characteristics and prognosis, and possibly also in risk factors. For subtypes defined by KRAS and BRAF mutation status, BMI is the only metabolic factor previously studied, with inconsistent findings. We investigated whether associations between BMI, blood glucose, blood lipids, and blood pressure and CRC risk differed by tumor KRAS and BRAF mutation status in 117,687 participants from two population‐based cohorts within the Northern Sweden Health and Disease Study (NSHDS). Hazard ratios (HRs) for overall CRC and CRC subtypes by metabolic factors were estimated with Cox proportional hazards regression, using multiple imputation to handle missing exposure and tumor data. During a median follow‐up of 15.6 years, we acquired 1,250 prospective CRC cases, of which 766 cases had complete baseline and molecular tumor data. Consistent with previous evidence, higher BMI, total cholesterol, triglyceride levels, and blood pressure were associated with an increased risk of overall CRC (HRs per 1 standard deviation increase: 1.07 to 1.12). These associations were similar regardless of CRC subtype by KRAS and BRAF mutation status (all p heterogeneity > 0.05). The same was true for subtypes based on microsatellite instability status. Poor metabolic health may therefore be a universal mechanism for colorectal cancer, acting across multiple developmental pathways. |
author2 |
Cancer Research Foundation in Northern Sweden Cancerfonden Medicinska fakulteten, Umeå Universitet |
format |
Article in Journal/Newspaper |
author |
Myte, Robin Gylling, Björn Häggström, Jenny Häggström, Christel Zingmark, Carl Löfgren Burström, Anna Palmqvist, Richard Van Guelpen, Bethany |
spellingShingle |
Myte, Robin Gylling, Björn Häggström, Jenny Häggström, Christel Zingmark, Carl Löfgren Burström, Anna Palmqvist, Richard Van Guelpen, Bethany Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status |
author_facet |
Myte, Robin Gylling, Björn Häggström, Jenny Häggström, Christel Zingmark, Carl Löfgren Burström, Anna Palmqvist, Richard Van Guelpen, Bethany |
author_sort |
Myte, Robin |
title |
Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status |
title_short |
Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status |
title_full |
Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status |
title_fullStr |
Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status |
title_full_unstemmed |
Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status |
title_sort |
metabolic factors and the risk of colorectal cancer by kras and braf mutation status |
publisher |
Wiley |
publishDate |
2019 |
url |
http://dx.doi.org/10.1002/ijc.32104 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fijc.32104 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.32104 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ijc.32104 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_source |
International Journal of Cancer volume 145, issue 2, page 327-337 ISSN 0020-7136 1097-0215 |
op_rights |
http://creativecommons.org/licenses/by-nc/4.0/ |
op_doi |
https://doi.org/10.1002/ijc.32104 |
container_title |
International Journal of Cancer |
container_volume |
145 |
container_issue |
2 |
container_start_page |
327 |
op_container_end_page |
337 |
_version_ |
1800758560620019712 |