Chronic alcohol drinking: Liver and pancreatic cancer?

Zakhari, Samir

doi:10.1016/j.clinre.2015.05.006

Cited by 7 publications

(7 citation statements)

References 45 publications

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“…A high content of fats in the diet shows a relationship with increased gut permeability and inflammation of adipose tissue [21]. Both alcohol consumption and smoking increase the risk of CRC, HCC and PC [23][24][25][26]. Long-term smoking has a toxic effect on the immune system, predisposing it to chronic low-grade systemic inflammation [27], while chronic alcohol consumption is associated with a disruption of cellular responses by lowering natural killer (NK) cells and T lymphocytes along with a change in cytokine expression compared to normal controls [26].…”

Section: The Most Common Inflammation-associated Risk Factors For Canmentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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Section: The Most Common Inflammation-associated Risk Factors For Canmentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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“…It included the statement: ‘While chronic abusive alcohol consumption is associated with a plethora of health problems including cancer, attributing cancer to social moderate drinking is simply incorrect and is not supported by the body of scientific literature’. The article was attributed to a former senior scientist in the United States now employed by an alcohol industry body, while continuing to publish on alcohol in the scientific literature .…”

Section: Introductionmentioning

confidence: 99%

Alcohol consumption as a cause of cancer

2016

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“…Retrospective study has shown that 20-25% of patients with pancreatic cancer develop diabetes mellitus 6-36 months before pancreatic cancer is diagnosed [5]. This observation is also being evaluated as a possible indication of early detection in this disease, in addition to alcohol abuse and chronic pancreatitis [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

Microbial Dysbiosis and polyamine metabolism as predictive markers for early detection of pancreatic cancer

Méndez

Kesh

Arora

et al. 2018

Preprint

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Synopsis:Gut microbiota changes during early stages of pancreatic ductal adenocarcinoma (PDAC) progression and contributes towards host polyamine pool. Both changes can be used as an early predictive marker for PDAC. Short title: Whole genome sequencing of PDAC microbiomeWord count: 4,735 Translational RelevancePancreatic carcinogenesis progresses through pre-cancerous PanIN lesions to invasive cancer. Even though these morphological changes are histologically distinct, imaging techniques are not able to distinguish the pre-invasive PanINs from normal pancreas, making detection of a tumor at a precancerous stage impossible . Thus, majority of cases (85-90%) present with advanced pancreatic cancer at the time of diagnosis. This contributes to the dismal survival rate in this disease. Our study of gut microbiome analysis on KPC mice during tumor progression followed by metabolic reconstruction and experimental validation in human samples indicate that gut-microbiome analysis along with an analysis of the microbial metabolites can be developed as potential biomarkers for detection of PDAC at early stages when histological changes are not yet grossly apparent. AbstractPurpose: The lack of tools for early detection of pancreatic ductal adenocarcinoma (PDAC) is directly correlated to the abysmal survival rate in patients. In addition to several potential detection tools under active investigation, we tested the gut microbiome and its metabolic complement as one of the earliest detection tools that could be useful in patients at high-risk for PDAC. Experimental Design:A combination of 16s pyrosequencing and whole-genome sequencing of gut microbiota was used in a spontaneous genetically engineered PDAC murine model (KRAS G12D TP53 R172H Pdx Cre or KPC). Metabolic reconstruction of microbiome was done using the HUmanN2 pipeline. Serum polyamine levels were measured from murine and patient samples using standard methods. Results:Results showed a progressive Proteobacterial and Firmicutes dominance in gut microbiota in early stages of PDAC development. Upon in silico reconstruction of active metabolic pathways within the altered microbial flora, polyamine and nucleotide biosynthetic pathways were significantly elevated.These metabolic products are known to be actively assimilated by the host and eventually utilized by rapidly dividing cells for proliferation validating their importance in the context of tumorigenesis. In KPC mice, as well as PDAC patients, we show significantly elevated serum polyamine concentration. Therefore, at the early stages of tumorigenesis, the gut microbial composition changes in a way to release metabolites that foster host tumorigenesis, thereby fulfilling the 'vicious cycle hypothesis' of the role of the microbiome in health and disease states. Conclusions:Our results provide a potential, precise, non-invasive tool for early detection of PDAC, which will result in improved outcomes.

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Chronic alcohol drinking: Liver and pancreatic cancer?

Cited by 7 publications

References 45 publications

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Alcohol consumption as a cause of cancer

Microbial Dysbiosis and polyamine metabolism as predictive markers for early detection of pancreatic cancer

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