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      Oral antibiotic use and early-onset colorectal cancer: findings from a case-control study using a national clinical database

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          Abstract

          Background

          Antibiotic-induced gut dysbiosis has been associated with colorectal cancer (CRC) in older adults. This study will investigate whether an association exists between antibiotic usage and early-onset colorectal cancer (CRC), and also evaluate this in later-onset CRC for comparison.

          Methods

          A case-control study was conducted using primary care data from 1999–2011. Analysis were conducted separately in early-onset CRC cases (diagnosed < 50 years) and later-onset cases (diagnosed ≥ 50 years). Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (CI) for the associations between antibiotic exposure and CRC by tumour location, adjusting for comorbidities.

          Results

          Seven thousands nine hundred and three CRC cases (445 aged <50 years) and 30,418 controls were identified. Antibiotic consumption was associated with colon cancer in both age-groups, particularly in the early-onset CRC cohort (<50 years: adjusted Odds Ratio (OR adj) 1.49 (95% CI 1.07, 2.07), p = 0·018; ≥50 years (OR adj (95% CI) 1.09 (1.01, 1.18), p = 0·029). Antibiotics were not associated with rectal cancer (<50 years: OR adj (95% CI) 1.17 (0.75, 1.84), p = 0.493; ≥50 years: OR adj (95% CI) 1.07 (0.96, 1.19), p = 0.238).

          Conclusion

          Our findings suggest antibiotics may have a role in colon tumour formation across all age-groups.

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          Most cited references64

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          Colorectal cancer statistics, 2020

          Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC occurrence based on incidence data (available through 2016) from population-based cancer registries and mortality data (through 2017) from the National Center for Health Statistics. In 2020, approximately 147,950 individuals will be diagnosed with CRC and 53,200 will die from the disease, including 17,930 cases and 3,640 deaths in individuals aged younger than 50 years. The incidence rate during 2012 through 2016 ranged from 30 (per 100,000 persons) in Asian/Pacific Islanders to 45.7 in blacks and 89 in Alaska Natives. Rapid declines in incidence among screening-aged individuals during the 2000s continued during 2011 through 2016 in those aged 65 years and older (by 3.3% annually) but reversed in those aged 50 to 64 years, among whom rates increased by 1% annually. Among individuals aged younger than 50 years, the incidence rate increased by approximately 2% annually for tumors in the proximal and distal colon, as well as the rectum, driven by trends in non-Hispanic whites. CRC death rates during 2008 through 2017 declined by 3% annually in individuals aged 65 years and older and by 0.6% annually in individuals aged 50 to 64 years while increasing by 1.3% annually in those aged younger than 50 years. Mortality declines among individuals aged 50 years and older were steepest among blacks, who also had the only decreasing trend among those aged younger than 50 years, and excluded American Indians/Alaska Natives, among whom rates remained stable. Progress against CRC can be accelerated by increasing access to guideline-recommended screening and high-quality treatment, particularly among Alaska Natives, and elucidating causes for rising incidence in young and middle-aged adults.
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            The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism.

            Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism.
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              Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data.

              Antibiotic drug consumption is a major driver of antibiotic resistance. Variations in antibiotic resistance across countries are attributable, in part, to different volumes and patterns for antibiotic consumption. We aimed to assess variations in consumption to assist monitoring of the rise of resistance and development of rational-use policies and to provide a baseline for future assessment. With use of sales data for retail and hospital pharmacies from the IMS Health MIDAS database, we reviewed trends for consumption of standard units of antibiotics between 2000 and 2010 for 71 countries. We used compound annual growth rates to assess temporal differences in consumption for each country and Fourier series and regression methods to assess seasonal differences in consumption in 63 of the countries. Between 2000 and 2010, consumption of antibiotic drugs increased by 36% (from 54 083 964 813 standard units to 73 620 748 816 standard units). Brazil, Russia, India, China, and South Africa accounted for 76% of this increase. In most countries, antibiotic consumption varied significantly with season. There was increased consumption of carbapenems (45%) and polymixins (13%), two last-resort classes of antibiotic drugs. The rise of antibiotic consumption and the increase in use of last-resort antibiotic drugs raises serious concerns for public health. Appropriate use of antibiotics in developing countries should be encouraged. However, to prevent a striking rise in resistance in low-income and middle-income countries with large populations and to preserve antibiotic efficacy worldwide, programmes that promote rational use through coordinated efforts by the international community should be a priority. US Department of Homeland Security, Bill & Melinda Gates Foundation, US National Institutes of Health, Princeton Grand Challenges Program. Copyright © 2014 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                leslie.samuel@nhs.scot
                Journal
                Br J Cancer
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group UK (London )
                0007-0920
                1532-1827
                17 December 2021
                17 December 2021
                1 April 2022
                : 126
                : 6
                : 957-967
                Affiliations
                [1 ]GRID grid.4777.3, ISNI 0000 0004 0374 7521, Centre for Public Health, School of Medicine, Dentistry & Biomedical Science, Queen’s University, ; Belfast, Northern Ireland
                [2 ]GRID grid.7107.1, ISNI 0000 0004 1936 7291, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, ; Aberdeen, Scotland
                [3 ]GRID grid.4777.3, ISNI 0000 0004 0374 7521, School of Pharmacy, Queen’s University, ; Belfast, Scotland
                [4 ]GRID grid.417581.e, ISNI 0000 0000 8678 4766, Department of Clinical Oncology, , Aberdeen Royal Infirmary, NHS Grampian, ; Aberdeen, Scotland
                Author information
                http://orcid.org/0000-0003-1415-7271
                http://orcid.org/0000-0001-9968-5991
                http://orcid.org/0000-0002-2689-4335
                http://orcid.org/0000-0002-8402-8670
                Article
                1665
                10.1038/s41416-021-01665-7
                8927122
                34921228
                79f16ec6-5b58-4307-8361-ffd6126ec2e5
                © The Author(s) 2021

                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/.

                History
                : 26 July 2021
                : 27 November 2021
                : 2 December 2021
                Categories
                Article
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                © Springer Nature Limited 2022

                Oncology & Radiotherapy
                cancer epidemiology,colon cancer
                Oncology & Radiotherapy
                cancer epidemiology, colon cancer

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