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Circulating branched-chain amino acids and long-term risk of obesity-related cancers in women
Obesity is a risk factor for > 13 cancer sites, although it is unknown whether there is a common mechanism across sites. Evidence suggests a role for impaired branched-chain amino acid (BCAAs; isoleucine, leucine, valine) metabolism in obesity, insulin resistance, and immunity; thus, we hypothesi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539150/ https://www.ncbi.nlm.nih.gov/pubmed/33024201 http://dx.doi.org/10.1038/s41598-020-73499-x |
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author | Tobias, Deirdre K. Hazra, Aditi Lawler, Patrick R. Chandler, Paulette D. Chasman, Daniel I. Buring, Julie E. Lee, I-Min Cheng, Susan Manson, JoAnn E. Mora, Samia |
author_facet | Tobias, Deirdre K. Hazra, Aditi Lawler, Patrick R. Chandler, Paulette D. Chasman, Daniel I. Buring, Julie E. Lee, I-Min Cheng, Susan Manson, JoAnn E. Mora, Samia |
author_sort | Tobias, Deirdre K. |
collection | PubMed |
description | Obesity is a risk factor for > 13 cancer sites, although it is unknown whether there is a common mechanism across sites. Evidence suggests a role for impaired branched-chain amino acid (BCAAs; isoleucine, leucine, valine) metabolism in obesity, insulin resistance, and immunity; thus, we hypothesized circulating BCAAs may be associated with incident obesity-related cancers. We analyzed participants in the prospective Women’s Health Study without a history of cancer at baseline blood collection (N = 26,711, mean age = 54.6 years [SD = 7.1]). BCAAs were quantified via NMR spectroscopy, log-transformed, and standardized. We used Cox proportional regression models adjusted for age, race, smoking, diet, alcohol, physical activity, menopausal hormone use, Body Mass Index (BMI), diabetes, and other risk factors. The endpoint was a composite of obesity-related cancers, defined per the International Agency for Research on Cancer 2016 report, over a median 24 years follow-up. Baseline BMI ≥ 30 kg/m(2) compared with BMI 18.5–25.0 kg/m(2) was associated with 23% greater risk of obesity-related cancers (n = 2751 events; multivariable HR 1.23, 95% CI 1.11–1.37). However, BCAAs were not associated with obesity-related cancers (multivariable HR per SD = 1.01 [0.97–1.05]). Results for individual BCAA metabolites suggested a modest association for leucine with obesity-related cancers (1.04 [1.00–1.08]), and no association for isoleucine or valine (0.99 [0.95–1.03] and 1.00 [0.96–1.04], respectively). Exploratory analyses of BCAAs with individual sites included positive associations between leucine and postmenopausal breast cancer, and isoleucine with pancreatic cancer. Total circulating BCAAs were unrelated to obesity-related cancer incidence although an association was observed for leucine with incident obesity-related cancer. |
format | Online Article Text |
id | pubmed-7539150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75391502020-10-08 Circulating branched-chain amino acids and long-term risk of obesity-related cancers in women Tobias, Deirdre K. Hazra, Aditi Lawler, Patrick R. Chandler, Paulette D. Chasman, Daniel I. Buring, Julie E. Lee, I-Min Cheng, Susan Manson, JoAnn E. Mora, Samia Sci Rep Article Obesity is a risk factor for > 13 cancer sites, although it is unknown whether there is a common mechanism across sites. Evidence suggests a role for impaired branched-chain amino acid (BCAAs; isoleucine, leucine, valine) metabolism in obesity, insulin resistance, and immunity; thus, we hypothesized circulating BCAAs may be associated with incident obesity-related cancers. We analyzed participants in the prospective Women’s Health Study without a history of cancer at baseline blood collection (N = 26,711, mean age = 54.6 years [SD = 7.1]). BCAAs were quantified via NMR spectroscopy, log-transformed, and standardized. We used Cox proportional regression models adjusted for age, race, smoking, diet, alcohol, physical activity, menopausal hormone use, Body Mass Index (BMI), diabetes, and other risk factors. The endpoint was a composite of obesity-related cancers, defined per the International Agency for Research on Cancer 2016 report, over a median 24 years follow-up. Baseline BMI ≥ 30 kg/m(2) compared with BMI 18.5–25.0 kg/m(2) was associated with 23% greater risk of obesity-related cancers (n = 2751 events; multivariable HR 1.23, 95% CI 1.11–1.37). However, BCAAs were not associated with obesity-related cancers (multivariable HR per SD = 1.01 [0.97–1.05]). Results for individual BCAA metabolites suggested a modest association for leucine with obesity-related cancers (1.04 [1.00–1.08]), and no association for isoleucine or valine (0.99 [0.95–1.03] and 1.00 [0.96–1.04], respectively). Exploratory analyses of BCAAs with individual sites included positive associations between leucine and postmenopausal breast cancer, and isoleucine with pancreatic cancer. Total circulating BCAAs were unrelated to obesity-related cancer incidence although an association was observed for leucine with incident obesity-related cancer. Nature Publishing Group UK 2020-10-06 /pmc/articles/PMC7539150/ /pubmed/33024201 http://dx.doi.org/10.1038/s41598-020-73499-x Text en © The Author(s) 2020 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Tobias, Deirdre K. Hazra, Aditi Lawler, Patrick R. Chandler, Paulette D. Chasman, Daniel I. Buring, Julie E. Lee, I-Min Cheng, Susan Manson, JoAnn E. Mora, Samia Circulating branched-chain amino acids and long-term risk of obesity-related cancers in women |
title | Circulating branched-chain amino acids and long-term risk of obesity-related cancers in women |
title_full | Circulating branched-chain amino acids and long-term risk of obesity-related cancers in women |
title_fullStr | Circulating branched-chain amino acids and long-term risk of obesity-related cancers in women |
title_full_unstemmed | Circulating branched-chain amino acids and long-term risk of obesity-related cancers in women |
title_short | Circulating branched-chain amino acids and long-term risk of obesity-related cancers in women |
title_sort | circulating branched-chain amino acids and long-term risk of obesity-related cancers in women |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539150/ https://www.ncbi.nlm.nih.gov/pubmed/33024201 http://dx.doi.org/10.1038/s41598-020-73499-x |
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