Causal relationship of sugar-sweetened and sweet beverages with colorectal cancer: a Mendelian randomization study

Liu, Cenqin; Zheng, Shuhao; Gao, Hui; Yuan, Xin; Zhang, Zhixin; Xie, Jiarong; Yu, Chaohui; Xu, Lei

doi:10.1007/s00394-022-02993-x

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…Llaha et al 41 discovered that the intake of sweetened beverages was not linked to the risk of CRC or PC development, consistent with our findings. However, Liu et al 42 performed an MR study and identified a positive association between the intake of sweetened beverages and colon cancer risk, but no causal association between the intake of sweetened beverages and rectal cancer or CRC was observed. The positive association was limited (OR = 1.01; 95% CI: 1.00–1.03), and we speculate that this association could be explained by disparities in ethnicity and tumor classification.…”

Section: Discussionmentioning

confidence: 99%

The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis

Cai,

Li,

Liang

et al. 2024

Sci Rep

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Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93–0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05–1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53–0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34–0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37–0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves’ disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs.

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Section: Discussionmentioning

confidence: 99%

The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis

Cai,

Li,

Liang

et al. 2024

Sci Rep

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“…Three principles genetic tools were followed for MR analysis: a. genetic tools were strongly correlated with corresponding exposures ( p < 5×10 -5 ), which could avoid the possibility of insufficient powered instrumental variables (IVs) and has been applied on previous studies ( 28 , 29 ); b. genetic tools were independent of outcomes and could only influence outcome through exposure; and c. when conducting MRs between air pollutions and COVID-19 risks, the genetic tools were independent of the mediators ( 30 ). The IVs of SNPs were conjugated using the PLINK algorithm (LD < 0.001 and < 10 MB from the index variant) to select independent IVs.…”

Section: Methodsmentioning

confidence: 99%

The causal relationship between air pollution, obesity, and COVID-19 risk: a large-scale genetic correlation study

Zhang,

Wen,

Wan

et al. 2023

Front. Endocrinol.

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ObjectiveObservational evidence reported that air pollution is a significant risk element for numerous health problems, such as obesity and coronavirus disease 2019 (COVID-19), but their causal relationship is currently unknown. Our objective was to probe the causal relationship between air pollution, obesity, and COVID-19 and to explore whether obesity mediates this association.MethodsWe obtained instrumental variables strongly correlated to air pollutants [PM2.5, nitrogen dioxide (NO2) and nitrogen oxides (NOx)], 9 obesity-related traits (abdominal subcutaneous adipose tissue volume, waist-to-hip ratio, body mass index, hip circumference, waist circumference, obesity class 1-3, visceral adipose tissue volume), and COVID-19 phenotypes (susceptibility, hospitalization, severity) from public genome-wide association studies. We used clinical and genetic data from different public biological databases and performed analysis by two-sample and two-step Mendelian randomization.ResultsPM2.5 genetically correlated with 5 obesity-related traits, which obesity class 1 was most affected (beta = 0.38, 95% CI = 0.11 - 0.65, p = 6.31E-3). NO2 genetically correlated with 3 obesity-related traits, which obesity class 1 was also most affected (beta = 0.33, 95% CI = 0.055 - 0.61, p = 1.90E-2). NOx genetically correlated with 7 obesity-related traits, which obesity class 3 was most affected (beta = 1.16, 95% CI = 0.42-1.90, p = 2.10E-3). Almost all the obesity-related traits genetically increased the risks for COVID-19 phenotypes. Among them, body mass index, waist circumference, hip circumference, waist-to-hip ratio, and obesity class 1 and 2 mediated the effects of air pollutants on COVID-19 risks (p < 0.05). However, no direct causal relationship was observed between air pollution and COVID-19.ConclusionOur study suggested that exposure to heavy air pollutants causally increased risks for obesity. Besides, obesity causally increased the risks for COVID-19 phenotypes. Attention needs to be paid to weight status for the population who suffer from heavy air pollution, as they are more likely to be susceptible and vulnerable to COVID-19.

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“…We also find that a rapid change in mitochondrial dynamics and function, is required for PNC survival during their rapid proliferative expansion. The excess glucose resource mediated PNC hyperproliferation might provide a mechanism linking dietary high sugar intake to cancer incidence that has been observed in humans 37,38 . Importantly, we provide evidence that the metabolic adaptation pathways might be targeted to selectively eliminate PNC through repurposing currently available drugs, thus might provide effective tumour prevention strategies for human with RAS driven cancer predisposition syndromes 39 .…”

Section: Drp1/dnml1 Inhibitor Mdivi Blocks Mitochondrial Fragmentatio...mentioning

confidence: 97%

Preneoplastic cells switch to Warburg metabolism from their inception exposing multiple vulnerabilities for targeted elimination

Myllymäki

Kelly

Elliot

et al. 2023

Preprint

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Otto Warburg first described tumour cells as displaying enhanced aerobic glycolysis whilst maintaining defective oxidative phosphorylation (OXPHOS) for energy production almost 100 years ago. Since then, the 'Warburg effect' has been widely accepted as a key feature of rapidly proliferating cancer cells. Targeting cancer metabolism is now being considered as a promising precision oncology therapeutic approach. What is not clear is how early "Warburg metabolism" initiates during cancer progression and whether changes in energy metabolism might influence tumour progression ab initio. We set out to investigate energy metabolism in HRASG12V driven preneoplastic cell (PNC) at inception, in a zebrafish skin PNC model; and to test how the impact of manipulating energy metabolism in the whole animal may impact PNC initiation. We find that, within 24 hours of HRASG12V induction, PNCs upregulate "Warburg metabolism", and that this is required for their expansion. We show that blocking glycolysis reduces PNC proliferation, whilst increasing available glucose both enhances PNC proliferation and also reduces apoptosis. Impaired OXPHOS of PNCs might be exploited therapeutically since a mild complex I inhibitor, metformin, selectively induces apoptosis and suppresses proliferation of PNCs. In addition, we find mitochondrial fragmentation in PNCs occur prior to metabolic alteration and this is important for their survival since exposure to Drp1/Dnml1 inhibitor, mdivi, which blocks mitochondrial fragmentation leads to enhanced PNC apoptosis. Our data indicate that altered energy metabolism is one of the earliest events upon oncogene activation in somatic cells, which provide a targeted and effective tumour prevention therapy.

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Causal relationship of sugar-sweetened and sweet beverages with colorectal cancer: a Mendelian randomization study

Cited by 7 publications

References 36 publications

The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis

The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis

The causal relationship between air pollution, obesity, and COVID-19 risk: a large-scale genetic correlation study

Preneoplastic cells switch to Warburg metabolism from their inception exposing multiple vulnerabilities for targeted elimination

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