The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Biohybrid polymer-antimicrobial peptide medium against Enterococcus faecalis.

Antimicrobial peptides (AMPs) are conserved evolutionary components of the innate immune system that are being tested as alternatives to antibiotics. Slow release of AMPs using biodegradable polymers can be advantageous in maintaining high peptide levels for topical treatment, especially in the oral environment in which dosage retention is challenged by drug dilution with saliva flow and by drug inactivation by salivary enzymatic activity. Enterococcus faecalis is a multidrug resistant nosocomial pathogen and a persistent pathogen in root canal infections. In this study, four ultra-short lipopeptides (C16-KGGK, C16-KLLK, C16-KAAK and C16-KKK) and an amphipathic α-helical antimicrobial peptide (Amp-1D) were tested against E. faecalis. The antibacterial effect was determined against planktonic bacteria and bacteria grown in biofilm. Of the five tested AMPs, C16-KGGK was the most effective. Next C16-KGGK was formulated with one of two polymers poly (lactic acid co castor oil) (DLLA) or ricinoleic acid-based poly (ester-anhydride) P(SA-RA). Peptide-synthetic polymer conjugates, also referred to as biohybrid mediums were tested for antibacterial activity against E. faecalis grown in suspension and in biofilms. The new formulations exhibited strong and improved anti-E. faecalis activity

Growth inhibition of <i>E. faecalis</i> by KGGK released from P(SA:RA) or from DLLA.

<p>The side walls of 6 wells from line A of a 96 microwell plate were coated with the tested formulation (100 μg peptide+100 mg polymer, ratio 1∶1000). Fresh medium was added to the first line of wells and was transferred every 24 hrs to a new line below for a week. Then the bacteria were added to the tested wells and the plate was incubated at 37°C in a VERSAmax microplate reader and OD₆₅₀ in each well was followed automatically for 20 hrs. (A, C) KGGK+DLLA. (B, C) KGGK+ P(SA:RA) (D, E) weekly release of both formulations. Percent growth inhibition calculated compared with that of the non- treated bacteria during the logarithmic phase of the non treated bacteria. Generation time was calculated from each curve using the section representing the exponential growth phase (C, E).</p

<i>E. faecalis</i> growth is inhibited by C16-KGGK but not by hBD3.

<p>Growth of <i>E. faecalis</i> was measured (see Materials and Methods) in the presence of increasing concentrations of hBD3 (A) or of the lipopeptide KGGK (B). Percent growth inhibition was calculated compared with that of untreated bacteria during the logarithmic phase of the non treated bacteria. Generation time was calculated from each curve using the section representing the exponential growth phase (C).</p

Anti <i>E. faecalis</i> MICs of the AMPs investigated.

<p>Underlined amino acids are D-enantiomers.</p><p>Anti <i>E. faecalis</i> MICs of the AMPs investigated.</p

Effect of KGGK incorporated in biodegradable polymer on ATP in <i>E. faecalis</i> biofilm.

<p>Biofilm was exposed to the formulation for 72 hrs and ATP was measured as described in Materials and Methods. <i>Ef</i> represents the untreated bacteria as control, <i>KGGK</i> - bacteria treated only with peptide<i>; formulation -</i> bacteria treated with sustained release peptide; <i>polymer -</i> bacteria treated only with polymer as control.</p

Effect of the antimicrobial peptides on the development of <i>E. faecalis</i> biofilms.

<p><i>E. faecalis</i> biofilms were grown in 96 microtiter plate wells for 72 hrs in the presence of KGGK formulated with P(SA:RA) (panel A), or formulated with DLLA (B,) or with soluble peptides (C). <i>Ef</i> represents the non-treated bacteria, <i>KGGK+EF</i> - bacteria treated only with peptide, <i>formulation+EF -</i> bacteria treated with polymer and peptide and <i>Ef + polymer -</i> bacteria treated only with polymer control). The biofilm was stained with 1% crystal violet measured at OD 595 nm (see Materials and Methods). The optical density of the polymers alone without the bacteria was subtracted from the results of the biofilm that came in contact with the formulation and the polymer.</p

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BackgroundUnderstanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally.MethodsThe GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented.FindingsGlobally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]).InterpretationThe leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden