Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD) is increasing in prevalence worldwide and has become the greatest potential risk for cirrhosis and hepatocellular liver cancer. Currently, the role of gut microbiota in the development of MASLD has become a research hotspot. The development of MASLD can affect the homeostasis of gut microbiota, and significant changes in the composition or abundance of gut microbiota and its metabolite abnormalities can influence disease progression. The regulation of gut microbiota is an important strategy and novel target for the treatment of MASLD with good prospects. In this paper, we summarize the role of gut microbiota and its metabolites in the pathogenesis of MASLD, and describe the potential preventive and therapeutic efficacy of gut microbiota as a noninvasive marker to regulate the pathogenesis of MASLD based on the "gut-hepatic axis", which will provide new therapeutic ideas for the clinic.

Second primary malignancies (SPMs) threaten long-term survival in head and neck squamous cell carcinoma (HNSCC). Advancing our understanding of the molecular events driving these secondary tumors is essential. This review has explicated molecular drivers of SPM development, including epigenetic alterations such as DNA hypermethylation, genetic polymorphisms affecting detoxification pathways, and shifts in gene and protein expression profiles. Disruptions in the p53 signaling pathway, immune-related pathways, and impairments in glutathione S-transferase-mediated detoxification, emerge as central contributors to SPM risk. Additionally, direct comparisons of tumor specimens with adjacent or distant normal mucosa highlight field cancerization biomarkers, underscoring widespread carcinogen-induced damage. Loss of heterozygosity at chromosome arm 13q, p53 overexpression in tumor-distant epithelia, and proteomic abnormalities in ostensibly healthy mucosa collectively promote a tumor-prone field that encourages the formation of independent secondary tumors. This interplay underscores a multifactorial landscape of SPM pathogenesis, involving genetic susceptibility, environmental exposures, and intricate epigenetic and transcriptomic networks. By recognizing and validating reliable biomarkers, clinicians may pinpoint high-risk patients with greater precision, intervene earlier, and customize follow-up protocols and treatment regimens. Ultimately, translating these insights into routine practice promises a more proactive, individualized approach to preventing SPMs in HNSCC.

Approximately 4% of all cancer cases worldwide are caused by alcohol consumption (oropharynx, larynx, esophagus, stomach, colorectum, liver and the female breast). Various mechanisms contribute to ethanol-mediated carcinogenesis, including the action of acetaldehyde, the first metabolite of ethanol oxidation and oxidative stress primarily promoted through the induction of cytochrome P4502E1. Acetaldehyde is toxic and carcinogenic, binds to DNA and proteins, inhibits the oxidative defense- and the nuclear repair system, and prevents DNA methylation. High levels of acetaldehyde occur through increased production in the presence of a hyperactive alcohol dehydrogenase (ADH1C*1,1) or decreased degradation in the presence of low active aldehyde dehydrogenase (ALDH2*1,2). In addition, microbes of the upper alimentary tract and the colorectum effectively produce acetaldehyde from ethanol. In addition, ethanol induces cytochrome P4502E1 resulting in an enhanced ethanol metabolism and the generation of reactive oxygen species (ROS). ROS may cause lipid peroxidation (LPO) with the LPO-products 4-hydroxynonenal or malondialdehyde, which may form highly carcinogenic etheno DNA-adducts CYP2E1 is also involved in the activation of a variety of dietary and tobacco procarcinogens and in the degradation of retinoic acid. Alcohol also influences tumor promotion, such as epigenetics with a change in DNA methylation and histone modification, and affects a variety of cancer genes and signaling pathways. Preventive measures include reducing alcohol consumption, quitting smoking and keeping good oral hygiene. Alcohol consumers - especially when they smoke or belong to genetic risk groups - should be regularly checked for cancer of the upper alimentary tract, for alcohol- associated liver disease, and for breast cancer. Cessation or reduction of alcohol consumption definitively reduces cancer risk.

Chronic pancreatitis (CP) is a known risk factor for pancreatic cancer; however its association to extra pancreatic (EP) cancers remains inadequately explored. The aim of this systematic review is to investigate the evidence for CP as a risk factor for developing EP cancers.

Electronic search was conducted on Ovid Medline, EMBASE and Scopus from inception to January 27, 2024 to identify patients with CP who developed EP cancers. Prevalence and incidence of each cancer were calculated where possible from the reported numbers. A random effects meta-analysis was used to pool prevalence, incidence and hazard ratios (HR) of each EP cancer. Heterogeneity was assessed using I2. PROSPERO registration: CRD42024543050.

Sixteen (16) studies consisting of 117,163 CP patients met the eligibility criteria. 4015 (3.4%) patients developed 4019 EP cancers. The overall annual prevalence and incidence of EP cancers were 7962 (95% CI 5044-10880) per 100,000 CP patients and 1039 (95% CI 649-1663) per 100,000 person years. Lung cancer had the highest annual prevalence - (1540 (95% CI 667-2413) per 100,000 CP patients) and incidence (260 (95% CI 120-390) per 100,000 person years). The pooled HR were 1.31 (95% CI 1.03-1.66) and 1.58 (95% CI 1.27-1.98) for adjusted lung cancer and crude liver cancer in patients with CP compared to patients without CP, respectively.

Patients with CP have an increased risk of developing EP cancers compared to patients without CP, in particular lung and liver cancer which had the highest relative risk. Shared risk factor modifications, such as smoking cessation and alcohol reduction, could lower the risk of common EP cancers. Further, implementing non-invasive screening measures may aid in early diagnosis in this high-risk group.

Cancers of the oral cavity, lip, salivary gland, and oropharynx cause substantial global disease burden. While tobacco-use and alcohol use are highly associated with oral cancers, the rising incidence of disease in patients who do not use tobacco or alcohol points to additional carcinogenic risk factors. Chronic inflammation, disruption of the oral microbiome, and dysbiosis are becoming more widely implicated in the pathogenesis of oral cancer. Several studies have identified specific bacterial species enriched in patients with oral cancer, including Porphyromonas gingivalis and Fusobacterium nucleatum. In this narrative review, we describe potential carcinogenic mechanisms exhibited by these species and other microbes in the development of oral cancer.

Alcohol is a known carcinogen, yet the evidence for an association with pancreatic cancer risk is considered as limited or inconclusive by international expert panels. We examined the association between alcohol intake and pancreatic cancer risk in a large consortium of prospective studies.

Population-based individual-level data was pooled from 30 cohorts across four continents, including Asia, Australia, Europe, and North America. A total of 2,494,432 participants without cancer at baseline (62% women, 84% European ancestries, 70% alcohol drinkers [alcohol intake ≥ 0.1 g/day], 47% never smokers) were recruited between 1980 and 2013 at the median age of 57 years and 10,067 incident pancreatic cancer cases were recorded. In age- and sex-stratified Cox proportional hazards models adjusted for smoking history, diabetes status, body mass index, height, education, race and ethnicity, and physical activity, pancreatic cancer hazard ratios (HR) and 95% confidence intervals (CI) were estimated for categories of alcohol intake and in continuous for a 10 g/day increase. Potential heterogeneity by sex, smoking status, geographic regions, and type of alcoholic beverage was investigated. Alcohol intake was positively associated with pancreatic cancer risk, with HR30-to-<60 g/day and HR≥60 g/day equal to 1.12 (95% CI [1.03,1.21]) and 1.32 (95% CI [1.18,1.47]), respectively, compared to intake of 0.1 to <5 g/day. A 10 g/day increment of alcohol intake was associated with a 3% increased pancreatic cancer risk overall (HR: 1.03; 95% CI [1.02,1.04]; pvalue < 0.001) and among never smokers (HR: 1.03; 95% CI [1.01,1.06]; pvalue = 0.006), with no evidence of heterogeneity by sex (pheterogeneity = 0.274) or smoking status (pheterogeneity = 0.624). Associations were consistent in Europe-Australia (HR10 g/day = 1.03, 95% CI [1.00,1.05]; pvalue = 0.042) and North America (HR10 g/day = 1.03, 95% CI [1.02,1.05]; pvalue < 0.001), while no association was observed in cohorts from Asia (HR10 g/day = 1.00, 95% CI [0.96,1.03]; pvalue = 0.800; pheterogeneity = 0.003). Positive associations with pancreatic cancer risk were found for alcohol intake from beer (HR10 g/day = 1.02, 95% CI [1.00,1.04]; pvalue = 0.015) and spirits/liquor (HR10 g/day = 1.04, 95% CI [1.03,1.06]; pvalue < 0.001), but not wine (HR10 g/day = 1.00, 95% CI [0.98,1.03]; pvalue = 0.827). The differential associations across geographic regions and types of alcoholic beverages might reflect differences in drinking habits and deserve more investigations.

Findings from this large-scale pooled analysis support a modest positive association between alcohol intake and pancreatic cancer risk, irrespective of sex and smoking status. Associations were particularly evident for baseline alcohol intake of at least 15 g/day in women and 30 g/day in men.

The cGAS-MITA/STING pathway plays critical roles in both host defense against DNA virus and intrinsic antitumor immunity by sensing viral genomic DNA or dis-located mitochondrial/cellular DNA. Whether carcinogenic metabolites can target the cGAS-MITA axis to promote tumorigenesis is unknown. In this study, we identified acetaldehyde, a carcinogenic metabolite, as a suppressor of the cGAS-MITA pathway. Acetaldehyde inhibits the DNA virus herpes simplex virus 1 (HSV-1)- and transfected DNA-triggered but not cGAMP-induced activation of downstream components and induction of downstream effector genes. Mechanistically, acetaldehyde impairs the binding of cGAS to DNA as well as the phase separation of the cGAS-DNA complex in cells. In mouse models, acetaldehyde inhibits antiviral cytokine production, promotes viral replication and lethality upon HSV-1 infection. In a colorectal tumor xenograft model, acetaldehyde promotes tumor growth and inhibits CD8+ T cell infiltration by targeting cGAS in both the tumor cells and immune cells in mice. Bioinformatic analysis indicates that expression of acetaldehyde dehydrogenase 2 (ALDH2), which converts acetaldehyde to acetic acid, is negatively correlated with stimulatory immune signatures in clinical colorectal tumors, and higher ALDH2 expression exhibits better prognosis of colorectal cancer patients. Collectively, our results suggest that acetaldehyde impairs cGAS activity to inhibit the cGAS-MITA axis, which contributes to its effects on carcinogenesis.

The prevalence of night-shift employment is on the rise among full-time and part-time workers globally. Those engaged in night-shift work encounter various biological challenges, including exposure to artificial light during nighttime and disruptions to their circadian rhythms. These factors, along with changes in daily routines and activities, may pose significant risks to the health of night workers. Notably, the number of individuals working overtime or on night shifts has increased across various sectors, particularly in transportation, healthcare, and manufacturing. The International Agency for Research on Cancer (IARC) has classified night-shift work as probably carcinogenic to humans (IARC Group 2A). Subsequent research has identified several potential mechanisms through which night-shift work may contribute to carcinogenicity: (1) disruption of circadian rhythms, (2) suppression of melatonin levels due to nighttime light exposure, (3) physiological alterations, (4) lifestyle changes, and (5) reduced vitamin D levels resulting from inadequate sunlight exposure. Colorectal cancer (CRC) poses a significant public health challenge, ranking as the second leading cause of cancer-related death worldwide in 2020. Other than CRC, other gastrointestinal cancers are also creating a great global health issue because of their morbidity and mortality rates. In this review, we highlight the role of night shifts in disturbing circadian rhythm and how this action leads to carcinogenesis in the GI tract.

This study examined the prognostic factors and genomic variations in oral squamous cell carcinoma (OSCC) among male and female patients, focusing on the rising incidence of OSCC in women.

Using data from 98 OSCC cases treated at National Taiwan University Hospital between 2013 and 2018, the study analyzed the patient cohort, clinical characteristics, and genomic profiles.

The Female patients had a higher incidence of tongue cancer, while the male patients were prone to have buccal cancer. Key prognostic factors included age over 55 years, tongue cancer, alcohol use in female patients as well as the buccal cancer, betel chewing, and smoking in male patients. Notably, women with tongue OSCC or without oral habits had poorer 5-year survival rates. Genomic analysis revealed the males with high-risk habits had elevated antigen-processing and reactive oxygen gene sets, whereas the low-risk females showed dysregulation in metabolic pathways. Immunologically, the female patients had fewer naïve B cells and higher suppressive M2 macrophages.

Our findings highlight distinct sex-related OSCC prognosis differences and suggest that personalized treatments targeting specific risk factors and genomic characteristics may improve the clinical outcomes, particularly for the female OSCC patients.

Cytochrome P450 (CYPs) superfamily of enzymes metabolize thousands of endogenous and exogenous substrates including ethanol. Results: Cytochrome P4502E1 (CYP2E1) is involved in ethanol metabolism as part of the so-called microsomal ethanol metabolizing system, in the metabolism of fatty acids and some drugs such as acetaminophen and isoniazid, and in the activation of a variety of procarcinogens (PCs). Chronic ethanol consumption induces CYP2E1 which may result in an enhanced metabolism of these drugs to their toxic intermediates, and in the generation of carcinogens. In addition, ethanol oxidation increases and is associated with the generation of reactive oxygen species (ROS). This oxidative stress is an important driver for the development of alcohol-associated liver disease (AALD) and alcohol-mediated cancer (AMC). ROS may bind directly to proteins and to DNA. ROS may also lead to lipid peroxidation (LPO) with the generation of LPO products. These LPO products may bind to DNA forming etheno-DNA adducts. Cell culture studies as well as animal experiments have shown that CYP2E1 knock-out animals or the inhibition of CYP2E1 by chemicals results in a significant improvement of liver histology. CYP2E1 is also involved in pathogenesis of hepatic steatosis and fibrosis. More recent studies in patients with AALD have demonstrated an improvement of serum transaminase activities when CYP2E1 was inhibited by clomethiazole. In addition to its role in the generation of ROS, CYP2E1 also enhances the activation of PCs and decreases the level of retinol and retinoic acid in the liver. Conclusion: Inhibition of CYP2E1 may improve AALD and may inhibit AMC.

This study explores how an active pharmaceutical ingredient-ionic liquid (API-IL), cholinium taurate ([Cho]+[Tau]-) IL, may alter the structural and functional stability of histone deacetylase 2 (HDAC2), which is a crucial enzyme linked to alcohol use disorder (AUD). A particular hallmark of AUD, which is a worldwide health burden, is epigenetic dysregulation, in which HDAC2 plays a significant role in gene silencing and chronic neuroplastic alterations. Leveraging the unique physicochemical properties of [Cho]+[Tau]-IL, including hydrogen bond (H-bond) formation and structural reinforcement, we explored its therapeutic potential through comprehensive computational approaches. Density functional theory (DFT) analyses provided insights into the hydration and stability profiles of [Cho]+[Tau]-IL, while 200 ns molecular dynamics (MD) simulations elucidated its interaction with HDAC2 at the molecular level. Strikingly, the [Tau]- ion emerged as a key modulator of HDAC2 stability, facilitating conformational transitions in the enzyme's secondary structure, notably from turns to helices. This stabilisation was mediated by intricate hydration networks, water-mediated H-bonds, and diverse non-covalent interactions (NCIs). The rigorous nature of our structural analyses confirmed the potential of [Cho]+[Tau]-IL as a robust stabiliser of HDAC2, offering a novel therapeutic avenue for AUD treatment. This work underscores the promise of API-ILs in targeting epigenetic regulators and advancing strategies for AUD, providing a solid foundation for future research in this area.

Cancer-related fatigue is a common and distressing symptom experienced by cancer patients, which may persist from the time of diagnosis to the end of life. This fatigue negatively affects patients' physical, emotional, and cognitive well-being. Nutrition plays a key role in managing cancer-related fatigue, and recently, the Mediterranean diet has gained attention as a potential intervention. The present study uses data from the National Health and Nutrition Examination Survey (NHANES) to investigate the association between cancer-related fatigue and the Mediterranean diet.

Data from the NHANES 2017-2020.03 cycle were selected for this cross-sectional study. The Alternative Mediterranean Diet Adherence (AMED) score was used to evaluate the participants' adherence to the Mediterranean diet. AMED scores were calculated based on data from 24-h dietary recall interviews conducted on both day one and day two. Multiple linear regression modeling was used to explore the association between AMED scores and cancer-related fatigue, as well as the relationship between AMED scores and fatigue in the general population.

A total of 6,413 adults aged 20 years and older were included in the study, with 707 identified as cancer patients. There was a noteworthy inverse relationship found between AMED scores and fatigue, which was more pronounced in cancer patients: β = -0.121, 95% CI: -0.172, -0.071 (p < 0.001) in the unadjusted model. This correlation remained significant after adjusting for all variables in model 3: β = -0.074, 95% CI: -0.127, -0.021 (p = 0.007). A significant dose-dependent relationship was found when AMED scores were expressed in quartiles, with a more pronounced negative association as AMED increased across all models (p for trend <0.05). In the cancer population, the analysis of individual nutrients and fatigue revealed that alcohol was significantly negatively associated with cancer-related fatigue in all models, particularly in the unadjusted model: β = -0.710, 95% CI: -1.058, -0.362 (p < 0.001). Subgroup analyses indicated that diabetes, education level and type of cancer had a significant effect on the relationship between AMED and fatigue, with interaction p-values of 0.010, 0.023 and 0.049, respectively.

The present study suggests that higher adherence to the Mediterranean diet may contribute to reduce fatigue, especially in cancer patients; however, further research is necessary to validate this correlation.

S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) and the ratio of SAM and SAH in Pb-exposed workers need to be assessed. In this study, we investigated the effects of Pb exposure on SAM, SAH, and methylation index (MI) in Pb-exposed workers with contemplation of lifestyle factors. Blood lead levels (BLLs), SAM, SAH, MI, and lifestyle factors were assessed in 338 male Pb-exposed workers. BLLs are estimated by ICP-OES method. SAM and SAH levels in serum were determined by ELISA method. The MI was calculated using SAM and SAH individual values. The lifestyle factors were collected using standard questionnaire. Levels of SAM and MI were significantly decreased with increased age, experience > 5 years, habits of tobacco chewing, smoking, alcohol consumption, and BLLs 10-30, 30-50, and > 50 µg/dL. Levels of SAH were significantly increased with increased age, habits of tobacco chewing and smoking, and BLLs 10-30, 30-50, and > 50 µg/dL. The association between BLLs and methylation index markers (SAM and MI) was reported as negative and significant. The association between BLLs and SAH was noted positive and significant. The influence of BLLs and lifestyle factors on SAM was noted at 12%, SAH at 35%, and MI at 27%, respectively. The highest percentage of influence was noted in SAH, followed by MI and SAM. In the workers exposed to Pb, lifestyle factors resulted in decreased SAM and MI and increased SAH levels. Adaptation of healthy lifestyle factors, personal hygiene practices, and use of PPE were suggested to minimize the reduction of methylation index markers.

This meta-analysis systematically investigates the markers of oxidative stress (OS) and antioxidant systems in the saliva and serum of patients with oral submucous fibrosis (OSF) and healthy controls.

Using a comprehensive search of databases from their inception period to December 31, 2023, articles related to OS or antioxidant markers in patients with OSF and healthy controls were retrieved. Literature screening and data extraction were performed by two reviewers according to the set criteria, and a third evaluator was involved in case of disagreements. The included studies were assessed with the Newcastle-Ottawa Scale, and the results were analyzed using Review Manager 5.4 software.

A total of 14 studies were included. Patients with OSF exhibited significantly higher levels of malondialdehyde (serum: SMD: 7.65, 95% confidence interval [CI]: 5.14-10.17, P < .00001, saliva: SMD: 3.07, 95% CI: 0.6-5.54, P < .00001) and 8-hydroxy-deoxyguanosine (saliva: SMD: 4.84, 95% CI: 3.49-6.18, P < .00001) than healthy controls. Levels of vitamin C (serum: SMD: -3.54, 95% CI: -4.10 to -2.99, P < .00001, saliva: SMD: -1.10, 95% CI: -1.39 to -0.80, P < .00001), vitamin E (saliva: SMD: -1.78, 95% CI: -2.1 to -1.45, P < .00001), and superoxide dismutase (serum: SMD: -9.77, 95% CI: -13.79 to -5.74, P < .00001) were significantly lower in patients with OSF than in healthy controls.

The results showed increased levels of OS markers and decreased levels of antioxidant markers in patients with OSF, providing valuable indicators that may aid in clinical diagnosis and management.

Alcohol-associated liver disease (ALD) represents a critical global health challenge characterized by liver damage resulting from excessive alcohol consumption. Early detection and timely intervention are essential for optimizing patient outcomes. However, the mechanisms underlying alcohol-induced liver injury have not been fully elucidated. Fibroblast growth factor 4 (FGF4) has been implicated in the progression of various liver diseases. This study aims to elucidate the role of FGF4 in the pathogenesis of ALD.

We analyzed human liver specimens and observed significant upregulation of FGF4 mRNA and protein levels in patients with ALD. Consistent findings were noted in mouse models subjected to a Lieber-DeCarli liquid diet. Importantly, hepatic FGF4 expression exhibited a positive correlation with ALD severity in both human subjects and murine models. Hepatocyte-specific deletion of Fgf4 ( Fgf4 -LKO) exacerbated alcohol-induced liver injury through increased oxidative stress, inflammation, and apoptosis. Specifically, Fgf4 -LKO mice demonstrated heightened susceptibility to ethanol plus CCl 4 -induced fibrosis and liver injury. However, treatment with the ERRγ inverse agonist GSK5182 and CYP2E1 inhibitor chlormethiazole (CMZ) mitigated the exacerbated liver injury associated with Fgf4 deficiency. Mechanistic investigations revealed that FGFR4 phosphorylates ERRγ, promoting its ubiquitination and degradation in hepatocytes. Hepatic-specific knockout of Fgfr4 intensified alcohol-induced liver injury and nullified the protective conferred of recombinant FGF4 △NT .

Our study identifies FGF4 as a stress-responsive regulator in liver pathophysiology, operating through an FGFR4-mediated ERRγ-CYP2E1 signaling pathway. These results underscore the potential of FGF4 and its downstream pathways as therapeutic targets for ALD treatment.

Diet is the primary and largely modifiable factor associated with breast cancer risk. However, inconsistent findings were evidenced in many epidemiological studies and resulted in a lack of conclusiveness. Therefore, this systematic review and meta-analysis aimed to explore dietary risk factors that may predict breast cancer among Ethiopian women.

A systematic review and meta-analysis was carried out. The articles were retrieved through electronic databases searching, including PubMed/Medline, Web of Science, Science Direct, EMBASE and Google Scholar. The Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument was applied for the critical appraisal. All case-control studies conducted in Ethiopia and reporting dietary factors of breast cancer in women were included in the final analysis.

Two independent reviewers extracted the data using a standardized data extraction format in Excel software. Stata version 17 software was used for the data analysis. Cochran's Q statistic with inverse variance (I2) was used to assess the presence of heterogeneity. A random effect model was used to estimate the odds ratio with a 95% confidence interval.

Overall, eight eligible articles with 2,774 women were included to explore the dietary predictors of breast cancer in Ethiopia. As a result, alcohol consumption (OR: 1.26, 95% CI: 1.01, 1.57), packed food intake (OR: 6.83; 95% CI: 4.56, 10.24), saturated fat/oil intake (OR: 1.51; 95% CI: 1.13, 2.02), meat consumption (OR: 6.08, 95% CI: 3.62, 10.22), and vegetable consumption (OR: 0.75, 95% CI: 0.49, 0.89) were identified as significant predictors of breast cancer among women in Ethiopia.

The current study revealed a significant relationship between dietary factors and breast cancer. Avoiding the consumption of alcohol, saturated fats/oils, packed foods, and meat, coupled with promotion of vegetable consumption, could substantially contribute to reduce the burden of breast cancer among women in Ethiopia. Therefore, policymakers and other concerned bodies should provide routine community-based nutrition education to raise public awareness about the contribution of women's dietary practices on their breast cancer risk.

Oral potentially malignant disorders (OPMDs), such as oral lichen planus (OLP) and oral leukoplakia (OLK), are clinical conditions associated with the risk of developing oral squamous cell carcinoma; however, no standardized treatment guidelines exist. Mutations in specific genes, known as oral cancer driver gene mutations (ODGMs), are responsible for carcinogenesis. We aimed to analyze the ODGMs in OPMDs and investigate their clinical correlations. We investigated 41 cases of OPMDs, including OLP and OLK, and performed next-generation sequencing using a custom gene panel targeting whole exons of TP53, HRAS, PIK3CA, NOTCH1, CDKN2A, FBXW7, and BRAF. We detected ODGMs in four OLK cases and one OLP case. All ODGM-positive OLK cases were located in the tongue, a site associated with a higher risk of malignant transformation compared with those in other oral sites. Moreover, ODGMs were significantly associated with alcohol consumption. While there was a tendency for mutations to increase with higher grades, we found no significant correlation between the presence of ODGMs and oral epithelial dysplasia (OED) grade. Notably, in the case of OLP with ODGM, the lesion histopathologically developed OED during the follow-up period, indicating an increased risk of cancer development and that cases with identified ODGMs require early surgical excision. These findings suggest that ODGM analysis may predict the risk of cancer development in OPMDs that are difficult to diagnose using histopathological examination alone.

Herein, the coordination bond connected porphyrin-MOFs/MXenes composites has been prepared to construct an electrochemical sensing system for in situ and real-time monitoring of H2O2 released by cells. The composites were synthesized by introducing 4-mercaptopyridine and utilizing its binding interaction with titanium in Mxenes and iron in MOFs. This composite was then transferred to the surface of ITO to construct an electrochemical sensing system. The unique properties of Mxenes and porphyrin MOFs endowed the sensing system with excellent electrocatalytic activity, good electrical conductivity and desirable biocompatibility. The electrochemical detections of hydroquinone verified the superior electrochemical performances of the sensing system. The constructed system achieved sensitive electrochemical detection of H2O2 with a detection limit of 3.1 µM and a linear range of 10 µM to 3 mM. Furthermore, the excellent biocompatibility of the composites ensured HeLa cells growth and proliferation on its surface. Based on these favorable properties, the sensing system successfully achieved in-situ and real-time monitoring of H2O2 released by HeLa cells.

High genetic risk and alcohol consumption ≥1 drink/day are associated with increased breast cancer risk. However, the interaction between alcohol and genetics on breast cancer risk is poorly understood, including in populations not enriched with daily drinkers. We prospectively studied 5,651 White and Black postmenopausal women in the Atherosclerosis Risk in Communities study. Alcohol intake was assessed by a food frequency questionnaire. The 313-SNP polygenic risk score (PRS) was calculated. Breast cancer cases were ascertained primarily by cancer registry linkage through 2015. Multivariable Cox regression was used to estimate HRs and 95% confidence intervals (CI) for the association of PRS and current ethanol intake with breast cancer, and their interaction. Of these individuals, 50.6% were current drinkers, and of them, 50.8% drank <1 drink/week and 12.8% drank >7 drinks/week. A higher PRS was associated with a higher breast cancer risk among White (HR1-SD, 1.48; 95% CI, 1.34-1.65) and Black (HR1-SD, 1.15; 95% CI, 0.96-1.38) women. Positive associations were not observed between current ethanol intake and breast cancer risk (White: HR13 g/week, 1.00; 95% CI, 0.98-1.03; Black: HR, 0.83; 95% CI, 0.69-1.00). Among both White and Black women, PRS generally seemed to be positively associated with risk in drinkers and nondrinkers. There was no evidence of a PRS-ethanol intake interaction among White or Black women. Patterns in Black women were similar when using an 89-SNP PRS developed among African ancestry women. In conclusion, in a prospective analysis of White and Black postmenopausal women in a study population not enriched with daily drinkers, our findings suggest that alcohol drinking does not modify the PRS-based genetic risk of breast cancer. Prevention Relevance: Although our findings suggest that alcohol drinking does not modify the PRS-based genetic risk of breast cancer among White and Black women with lower alcohol intake, nevertheless, women should consider limiting alcohol consumption as a general cancer prevention strategy, as indicated in dietary guidelines.

The incidence of alcohol-associated cancers is higher within Asian populations having an increased prevalence of an inactivating mutation in aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme required for the clearance of acetaldehyde, a cytotoxic metabolite of ethanol. The role of alcohol consumption in promoting lung cancer is controversial, and little attention has been paid to the association between alcohol drinking and pulmonary ALDH2 expression.

We performed a comprehensive bioinformatic analysis of multi-omics data available in public databases to elucidate the role of ALDH2 in lung adenocarcinoma (LUAD).

Transcriptional and proteomic data indicate a substantial pulmonary expression of ALDH2, which is functional for the metabolism of alcohol diffused from the bronchial circulation. ALDH2 expression is higher in healthy lung tissue than in LUAD and inhibits cell cycle, apoptosis, and epithelial-mesenchymal transition pathways. Moreover, low ALDH2 mRNA levels predict poor prognosis and low overall survival in LUAD patients. Interestingly, ALDH2 expression correlates with immune infiltration in LUAD.

A better understanding of the role of ALDH2 in lung tumor progression and immune infiltration might support its potential use as a prognostic marker and therapeutic target for improving immunotherapeutic response.

Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy with limited survival due to late stage diagnosis and scarce therapeutic options. Emerging evidence highlights the role of the "exposome," which encompasses environmental, lifestyle, and metabolic exposures, as a crucial determinant in PDAC risk and a potential avenue for early detection. This review synthesizes findings on modifiable risk factors, including smoking, obesity, diabetes, diet, and alcohol consumption, and their interplay with genetic and metabolic profiles in PDAC development. Additionally, we explore cutting-edge approaches in exposomic research, such as biobanking, electronic health record analysis, and AI-driven predictive models, to identify early biomarkers and stratify high-risk populations. This integrated framework aims to inform prevention strategies and improve early detection of PDAC.

The polymorphic microbiome is considered a new hallmark of cancer. Advances in High-Throughput Sequencing have fostered rapid developments in microbiome research. The interaction between cancer cells, immune cells, and microbiota is defined as the immuno-oncology microbiome (IOM) axis. Fungal microbes (the mycobiome), although representing only ∼ 0.1-1% of the microbiome, are a critical immunologically active component of the tumor microbiome. Accumulating evidence suggests a possible involvement of commensal and pathogenic fungi in cancer initiation, progression, and treatment responsiveness. The tumor-associated mycobiome mainly consists of the gut mycobiome, the oral mycobiome, and the intratumoral mycobiome. However, the role of fungi in cancer remains poorly understood, and the diversity and complexity of analytical methods make it challenging to access this field. This review aims to elucidate the causal and complicit roles of mycobiome in cancer development and progression while highlighting the issues that need to be addressed in executing such research. We systematically summarize the advantages and limitations of current fungal detection and analysis methods. We enumerate and integrate these recent findings into our current understanding of the tumor mycobiome, accompanied by the prospect of novel and exhilarating clinical implications.

Uncertainty remains regarding the role of diet in colorectal cancer development. We examined associations of 97 dietary factors with colorectal cancer risk in 542,778 Million Women Study participants (12,251 incident cases over 16.6 years), and conducted a targeted genetic analysis in the ColoRectal Transdisciplinary Study, Colon Cancer Family Registry, and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Alcohol (relative risk per 20 g/day=1.15, 95% confidence interval 1.09-1.20) and calcium (per 300 mg/day=0.83, 0.77-0.89) intakes had the strongest associations, followed by six dairy-related factors associated with calcium. We showed a positive association with red and processed meat intake and weaker inverse associations with breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. Genetically predicted milk consumption was inversely associated with risk of colorectal, colon, and rectal cancers. We conclude that dairy products help protect against colorectal cancer, and that this is driven largely or wholly by calcium.

Formaldehyde and acetaldehyde are reactive, small compounds that humans are exposed to routinely, variously from endogenous and exogenous sources. Both small aldehydes are classified as human carcinogens. Investigation of the DNA damaging properties of these two compounds began some 50 years ago. In this review, we summarize progress in this field since its inception over half a century ago, distilling insights gained by the collective efforts of many research groups while highlighting areas for future directions. Over the decades, general consensus about aspects of the mutagenicity of formaldehyde and acetaldehyde has been reached. But other characteristics of formaldehyde and acetaldehyde remain incompletely understood and require additional investigation. These include crucial details about the mutational signature(s) induced and possible mechanistic role(s) during carcinogenesis.

Cellular volatile organic compound (VOC) detection is crucial for studying lung cancer biomarkers. However, the reported VOC biomarkers from the same cell line seem to be inconsistent across different research groups. It is possibly related to the variation in culture media, and the result obtained by a conventional single medium approach (SMA) depends on what medium is used in the cell experiment. This study proposes a multiple media approach (MMA) to investigate reproducible characteristic VOCs of lung cancer cells. Using solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) in combination with untargeted analysis, we conducted two independently repetitive experiments to compare lung cancer cells (A549) and normal lung cells (BEAS-2B) under three culture media conditions (RPMI 1640, DMEM, and Ham's F12). Both experiments indicated that, compared with 62-96 VOCs obtained by the SMA, only two VOCs (3-methyl-1-butanol and 2-methyl-1-butanol) were reproducibly achieved by the MMA. Moreover, their concentrations were significantly lower in lung cancer cells than in normal cells. Further targeted analysis confirmed the downregulation trend of both VOCs in subcutaneous and primary tumor tissues from the lung cancer model mouse. The present work demonstrated that the MMA cell experiment, just like the multicenter trials for cell lines, can facilitate the discovery of reproducible characteristic VOCs. This provides a cellular experimental basis and scientific evidence for lung cancer biomarker investigation and even breath biopsy technique development.

The mortality of colorectal cancer (CRC) is increasing year by year and poses a significant global health burden. Many studies have demonstrated that alcohol consumption is an important risk factor for CRC and is closely associated with malignant metastasis in CRC patients, which in turn leads to a poor prognosis.

This study aimed to quantify the global, regional, and national burden of alcohol-related CRC between 1990 and 2021. First, numbers and age-standardized rates of deaths and disability-adjusted life years (DALYs) for alcohol-related CRC in 2021 were analyzed at different levels. Temporal trends in the burden of disease from 1990 to 2021 were analyzed through linear regression models. Finally, both Age-Period-Cohort (APC) models and Bayesian Age-Period-Cohort (BAPC) models were utilized to project the future burden of the disease for 2022-2046.

The global burden of disease for alcohol-related CRC is higher in 2021 compared to 1990. Male and older age groups are at high risk. Disease burden varies very much between Sociodemographic Index (SDI) regions, Global Burden of Disease (GBD) regions and countries. From 1990 to 2021, the number of cases increased, but the Age-Standardized Rate (ASR) decreased. The trends in disease burden predicted by the two models for 2022-2046 were not consistent.

This study describes the burden of disease in alcohol-related CRC and emphasizes that alcohol is a non-negligible risk factor for CRC. In order to mitigate harm, we need to strengthen disease surveillance, early prevention, timely detection, and improved treatment measures, with different approaches and responses for different regions.

Alcohol consumption has been consistently linked to an increased risk of several cancers, including breast and ovarian cancer. Despite substantial evidence supporting this association, the precise mechanisms underlying alcohol's contribution to cancer pathogenesis remain incompletely understood. This narrative review focuses on the key current literature on the biological pathways through which alcohol may influence the development of breast and ovarian cancer. Key mechanisms discussed include the modulation of estrogen levels, the generation of reactive oxygen species, the production of acetaldehyde, the promotion of chronic inflammation, and the induction of epigenetic changes. Alcohol's impact on estrogenic signaling, particularly in the regulation of estrogen and progesterone, is explored in the context of hormone-dependent cancers. Additionally, the role of alcohol-induced DNA damage, mutagenesis, and immune system modulation in tumor initiation and progression is examined. Overall, this review emphasizes the importance of alcohol as a modifiable risk factor for breast and ovarian cancer and highlights the need for further research to clarify its role in cancer biology.

Chronic liver disease is characterised by persistent inflammation, tissue damage, and regeneration, which leads to steatosis, fibrosis, and, lastly, cirrhosis and hepatocellular carcinoma (HCC). HCC, the most prevalent form of primary liver cancer, is one of the leading causes of cancer-related mortality worldwide. The gut microbiota plays a fundamental role in human physiology, and disturbances in its critical balance are widely recognised as contributors to various pathological conditions, including chronic liver diseases, both infectious and non-infectious in nature. Growing interest in microbiota research has recently shifted the focus towards the study of intratumoural microbiota, referred to as the "oncobiome", which can significantly impact the development and progression of HCC. In this review, we discuss existing research and provide an overview of the microbiota influence on viral hepatitis, particularly in shaping the progression of liver disease caused by the hepatitis B and hepatitis C viruses. We also explore microbial dysbiosis and its contribution to the silent and dangerous progression of non-alcoholic fatty liver disease. Additionally, we address the impact of alcohol on the liver and its interaction with the microbiota, tracing the pathway from inflammation to cirrhosis and cancer. The review emphasises the most common etiologies of hepatocellular carcinoma.

Of all new cases of colorectal cancer, Lynch syndrome (LS) accounts for approximately 3%. This syndrome is the most common hereditary cancer syndrome and is caused by pathogenic variants in the genes responsible for DNA mismatch repair. Although the relationship between colorectal cancer risk and diet is well established, little is known regarding the influence of diet and nutritional characteristics on LS's clinical evolution. There is some evidence suggesting that individuals living with LS should follow general guidelines for diet and alcohol restriction/moderation, so as to achieve and maintain a favorable weight status and overall health and quality of life. However, more research is needed, preferentially from clinical studies of a prospective nature with robust designs, to better inform diet and behavioral patterns targeting cancer prevention in LS.

Susceptibility to some cancers is linked to methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the Controlling Nutritional Status (CONUT) score in some populations. However, their relationship with susceptibility to colorectal cancer (CRC) susceptibility in the Hakka Chinese population remains unclear.

In total, 620 CRC patients and 734 controls were enrolled. MTHFR rs1801133 was genotyped, medical records (age, sex, smoking history, alcohol consumption, hypertension, diabetes mellitus, and family history of cancer, and blood cell parameters) were collected, and the relationship between this information and CRC susceptibility was analyzed.

There were significant differences in the distribution of CONUT classification (p=0.002), and proportions of history of smoking (p<0.001), hypertension (p<0.001), diabetes mellitus (p<0.001), and family history of cancer (p=0.002) between patients and controls. There were statistically significant differences in MTHFR rs1801133 genotypes distribution (58.7% C/C, 35.5% C/T, and 5.8% T/T in patients vs 65.5%, 31.2%, and 3.3% in controls, p=0.010) and allele distribution (76.5% C, and 23.5% T allele in patients vs 81.1%, and 18.9% in controls, p=0.003) between patients and controls. Logistic regression analysis indicated that non-normal CONUT range (non-normal vs normal, odds ratio (OR): 1.451, 95% confidence interval (CI): 1.119-1.882, p=0.005), and MTHFR rs1801133 variant (C/T + T/T vs C/C, OR: 1.373, 95% CI: 1.091-1.728, p=0.007), older age (≥65 vs <65 years, OR: 1.298, 95% CI: 1.023-1.646, p=0.032), male sex (OR: 1.354, 95% CI: 1.067-1.718, p=0.013), and history of alcohol drinking (OR: 2.232, 95% CI: 1.164-4.282, p=0.016) were independently associated with CRC risk.

Individuals carried MTHFR rs1801133 variant and with non-normal CONUT range, advanced age, history of alcohol consumption may be at increased CRC risk in the Hakka population.

Diet and exercise are modifiable lifestyle factors known to have a major influence on metabolism. Clinical practice addresses diseases of altered metabolism such as diabetes or hypertension by altering these factors. Despite enormous public interest, there are limited defined diet and exercise regimens for cancer patients. Nevertheless, the molecular basis of cancer has converged over the past 15 years on an essential role for altered metabolism in cancer. However, our understanding of the molecular mechanisms that underlie the impact of diet and exercise on cancer metabolism is in its very early stages. In this work, we propose conceptual frameworks for understanding the consequences of diet and exercise on cancer cell metabolism and tumor biology and also highlight recent developments. By advancing our mechanistic understanding, we also discuss actionable ways that such interventions could eventually reach the mainstay of both medical oncology and cancer control and prevention.

Heavy alcohol intake induces a wide spectrum of liver diseases ranging from steatosis, steatohepatitis, cirrhosis, and HCC. Although alcohol consumption is a well-known risk factor for the development, morbidity, and mortality of HCC globally, alcohol-associated hepatocellular carcinoma (A-HCC) is poorly characterized compared to viral hepatitis-associated HCC. Most A-HCCs develop after alcohol-associated cirrhosis (AC), but the direct carcinogenesis from ethanol and its metabolites to A-HCC remains obscure. The differences between A-HCC and HCCs caused by other etiologies have not been well investigated in terms of clinical prognosis, genetic or epigenetic landscape, molecular mechanisms, and heterogeneity. Moreover, there is a huge gap between basic research and clinical practice due to the lack of preclinical models of A-HCC. In the current review, we discuss the pathogenesis, heterogeneity, preclinical approaches, epigenetic, and genetic profiles of A-HCC, and discuss the current insights into and the prospects for future research on A-HCC. The potential effect of alcohol on cholangiocarcinoma and liver metastasis is also discussed.

The exposure of ethanol increases the risk of head and neck inflammation and tumor progression. However, limited studies have investigated the composition and functionality of laryngeal microbiota under ethanol exposure. We established an ethanol-exposed mouse model to investigate the changes in composition and function of laryngeal microbiota using Metagenomic shotgun sequencing. In the middle and late stages of the experiment, the laryngeal microbiota of mice exposed to ethanol exhibited obvious distinguished from that of the control group on principal-coordinate analysis (PCoA) plots. Among the highly abundant species, Salmonella enterica and Mycobacterium marinum were likely to be most impacted. Our findings indicated that the exposure to ethanol significantly increased their abundance in larynxes in mice of the same age, which has been confirmed through FISH experiments. Among the species-related functions and genes, metabolism is most severely affected by ethanol. The difference was most obvious in the second month of the experiment, which may be alleviated later because the animal established tolerance. Notable enrichments concerning energy, amino acid, and carbohydrate metabolic pathways occurred during the second month under ethanol exposure. Finally, based on the correlation between species and functional variations, a network was established to investigate relationships among microbiota, functional pathways, and related genes affected by ethanol. Our data first demonstrated the continuous changes of abundance, function and their interrelationship of laryngeal microbiota under ethanol exposure by Metagenomic shotgun sequencing.

Ethanol may participate in the inflammation and tumor progression by affecting the composition of the laryngeal microbiota. Here, we applied the metagenomic shotgun sequencing instead of 16 S rRNA sequencing method to identify the laryngeal microbiota under ethanol exposure. Salmonella enterica and Mycobacterium marinum are two dominant species that may play a role in the reconstruction of the laryngeal microenvironment, as their local abundance increases following exposure to ethanol. The metabolic function is most evidently impacted, and several potential metabolic pathways could be associated with alterations in microbiota composition. These findings could help us better understand the impact of prolonged ethanol exposure on the microbial composition and functionality in the larynx.

We discuss the article by Koizumi et al published in the World Journal of Gastroenterology. Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease (ALD) and the mechanism of action of elafibranor (EFN), a dual agonist of peroxisome proliferator-activated receptor α (PPARα) and peroxisome PPAR δ (PPARδ). EFN is currently in phase III clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease and primary biliary cholangitis. ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis (ASH), with chronic ASH eventually leading to fibrosis, cirrhosis, and, in some cases, hepatocellular carcinoma. The pathogenesis of ALD is driven by hepatic steatosis, oxidative stress, and acetaldehyde toxicity. Alcohol consumption disrupts lipid metabolism by inactivating PPARα, exacerbating the progression of ALD. EFN primarily activates PPARα, promoting lipolysis and β-oxidation in ethanol-stimulated HepG2 cells, which significantly reduces hepatic steatosis, apoptosis, and fibrosis in an ALD mouse model. Additionally, alcohol disrupts the gut-liver axis at several interconnected levels, contributing to a proinflammatory environment in the liver. EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy, inhibiting apoptosis and inflammatory responses, and enhancing intestinal barrier function through PPARδ activation.

The health effects of alcohol consumption, particularly regarding potential protective benefits of light to moderate intake compared to abstinence, remain a subject of ongoing debate. However, epidemiological studies face limitations due to imprecise exposure measurements and the potential for bias through residual confounding and reverse causation. To address these limitations, we conducted a systematic review of Mendelian Randomization (MR) studies examining the causal relationship between alcohol consumption and cancers, cardiovascular, liver, and neurological diseases.

We searched PubMed, ScienceDirect and Embase and Europe PMC up to 05/2024 for MR studies investigating the association of genetically predicted alcohol consumption with cancers, cardiovascular, liver and neurological diseases. We assessed methodological quality based on key elements of the MR design a genetic association studies tool.

We included 70 MR studies that matched our inclusion criteria. Our review showed a significant association of alcohol consumption with multiple cancers such as oral and oropharyngeal, esophageal, colorectal cancers, hepatocellular carcinoma and cutaneous melanoma. While the available studies did not consistently confirm the adverse or protective effects of alcohol on other cancers, such as lung cancer, as suggested by observational studies. Additionally, MR studies confirmed a likely causal effect of alcohol on the risk of hypertension, atrial fibrillation, myocardial infraction and vessels disease. However, there was no evidence to support the protective effects of light to moderate alcohol consumption on cognitive function, Alzheimer's disease, and amyotrophic lateral sclerosis, as reported in observational studies while our review revealed an increased risk of epilepsy and multiple sclerosis. The available studies provided limited results on the link between alcohol consumption and liver disease.

Despite the valuable insights into the causal relationship between alcohol consumption and various health outcomes that MR studies provided, it is worth noting that the inconsistent ability of genetic instrumental variables to distinguish between abstainers, light and moderate drinkers makes it difficult to differentiate between U or J-shaped vs. linear relationships between exposure and outcome. Additional research is necessary to establish formal quality assessment tools for MR studies and to conduct more studies in diverse populations, including non-European ancestries.

www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246154, Identifier: PROSPERO (CRD42021246154).

Alcohol-associated liver disease (ALD) poses a significant risk for hepatocellular carcinoma (HCC), comprising various liver conditions from steatosis to cirrhosis. Despite accounting for a third of global HCC cases and deaths, ALD-related HCC lacks characterization compared to viral hepatitis-related HCC. Proposed mechanisms for ALD-related HCC include acetaldehyde toxicity, increased reactive oxygen species, and inflammation. This review examines ALD-associated HCC epidemiology, co-factors like viral hepatitis and metabolic syndrome, surveillance, and treatment challenges. Despite advances in screening and management, ALD-related HCC often presents at advanced stages, limiting treatment options and survival.

The use of the comet assay in large biomonitoring studies may present logistical and technical challenges because of the processing of numerous samples. Proper sample preservation becomes imperative to prevent spurious DNA breakage. Previous research has shown the feasibility of conducting the comet assay on frozen blood samples, highlighting the potential of freezing at - 80 °C in preserving DNA integrity. Nonetheless, this approach presents challenges, including potential DNA damage during freezing and thawing, variability in processing, and the need for standardized protocols. Our objective was to evaluate whether there are comparable results in DNA migration assessed by the comet assay between fresh and frozen blood samples on a larger scale (N = 373). In our findings, elevated DNA migration was evident in frozen samples relative to fresh ones. Additionally, smoking, alcohol consumption, and season were linked to increased DNA damage levels in whole blood cells. Based on our results and available literature, conducting the comet assay on frozen blood samples emerges as a practical and efficient approach for biomonitoring and epidemiological research. This method enables the assessment of DNA damage in large populations over time, with samples, if properly cryopreserved, that may be used for years, possibly even decades. These observations hold significant implications for large-scale human biomonitoring and long-term epidemiological studies, particularly when samples are collected during fieldwork or obtained from biobanks. Continued method optimization and validation efforts are essential to enhance the utility of this approach in environmental and occupational health studies, emphasizing caution when comparing data obtained between fresh and frozen blood samples.