23 February 2022 In Cancer

BACKGROUND: The dose-response association between alcohol consumption and the subsequent pancreatic cancer risk by individuals' glycaemic status is unclear.

RESEARCH DESIGN AND METHOD: This large-scale nationwide cohort study included 9,514,171 adults without cancer who underwent health examinations under the Korean National Health Insurance Service in 2009 and were followed-up until December 2017 for pancreatic cancer development. Multivariable Cox proportional hazards regression analysis was performed.

RESULTS: During a median follow-up period of 7.3 years, 12,818 patients were newly-diagnosed with pancreatic cancer. Among individuals with normoglycemia, a J-shaped association was observed between the frequency of alcohol consumption (1-2 and >/=5 days/week: hazards ratio [HR]; 95% CI, 0.91; 0.85-0.97 and 1.13; 1.002-1.27, respectively) and pancreatic cancer risk, after adjusting for potential confounders. However, in patients with impaired fasting glucose (IFG), pancreatic cancer risk increased with increased frequency and average daily amount of alcohol consumption (all P for trend <0.01). IFG combined with heavy alcohol consumption (30 g/day) was associated with 38% increased pancreatic cancer risk (HR, 1.38; 95% CI, 1.23-1.54). Diabetes was associated with an increased pancreatic cancer risk regardless of alcohol consumption and 70% increased risk even in non-drinkers (HR, 1.70; 95% CI, 1.61-1.80).

CONCLUSIONS: The J-shaped dose-response association between alcohol consumption and pancreatic cancer risk was observed only in individuals with normoglycemia, not in patients with IFG and diabetes. Complete alcohol abstinence may help reduce pancreatic cancer risk in patients with IFG and diabetes.

23 February 2022 In Cancer

Alcohol consumption is thought to be one of the modifiable risk factors for colorectal cancer (CRC). However, the causality and mechanisms by which alcohol exerts its carcinogenic effect are unclear. We evaluated the association between alcohol consumption and CRC risk by analyzing data from 32 cohort studies and conducted two-sample Mendelian randomization (MR) analysis to examine for casual relationship.

To explore the effect of alcohol related DNA methylation on CRC risk, we performed an epigenetic MR analysis with data from an epigenome-wide association study (EWAS). We additionally performed gene-alcohol interaction analysis nested in the UK Biobank to assess effect modification between alcohol consumption and susceptibility genes. We discovered distinct effects of alcohol on CRC incidence and mortality from the meta-analyses, and genetic predisposition to alcohol drinking was causally associated with an increased CRC risk (OR = 1.79, 95% CI: 1.23-2.61) using two-sample MR approaches.

In epigenetic MR analysis, two alcohol-related CpG sites (cg05593667 and cg10045354 mapped to COLCA1/COLCA2 gene) were identified causally associated with an increased CRC risk (P < 8.20 x 10(-4) ). Gene-alcohol interaction analysis revealed that carriage of the risk allele of the eQTL (rs3087967) and mQTL (rs11213823) polymorphism of COLCA1/COLCA2 would interact with alcohol consumption to increase CRC risk (PInteraction = .027 and PInteraction = .016).

Our study provides comprehensive evidence to elucidate the role of alcohol in CRC and highlights that the pathogenic effect of alcohol on CRC could be partly attributed to DNA methylation by regulating the expression of COLCA1/COLCA2 gene.

23 February 2022 In Cancer

BACKGROUND: Heavy alcohol use is associated with increased risk of alcohol-related health consequences. Alcohol consumption has increased in females in the last fifteen years and females are more likely to experience exacerbated health risks due to drinking. Our group identified that females with AUD were more likely to report respiratory conditions or cancers compared to their male counterparts. This analysis sought to further examine relationships between sex and alcohol use on medical conditions by using the new 2020 U.S. Dietary Guidelines risk drinking levels.

METHODS: Data from the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; n = 36,309) was used to evaluate associations between sex (female vs. male) and alcohol risk drinking levels (abstainer, binge, heavy, extreme binge vs. moderate drinking) on past year self-reported doctor-confirmed medical conditions).

RESULTS: Females were 1.5 to 2 times more likely to have pain, respiratory, or other medical conditions in the past year (odds ratio [OR]=1.46–2.11) vs. males. Significant interactions demonstrated that heavy drinking females or extreme binge drinking females were 2 to 3 times more likely to have cancers or other conditions (OR=1.95–2.69) vs. males at the same risk drinking level. Female abstainers were more likely than male abstainers to have other medical conditions (OR=1.77).

CONCLUSIONS: Consistent with our previous findings, results identify that higher risk drinking levels are associated with the presence of past year self-reported doctor-confirmed medical conditions spanning organ systems, particularly in females. Treatment for high-risk drinking should be considered in the clinical care of individuals with significant medical conditions.

26 January 2022 In Liver Disease

The diagnosis of metabolic-associated fatty liver disease is based on the detection of liver steatosis together with the presence of metabolic dysfunction. According to this new definition, the diagnosis of metabolic-associated fatty liver disease is independent of the amount of alcohol consumed.

Actually, alcohol and its metabolites have various effects on metabolic-associated abnormalities during the process of alcohol metabolism. Studies have shown improved metabolic function in light to moderate alcohol drinkers. There are several studies focusing on the role of light to moderate alcohol intake on metabolic dysfunction.

However, the results from studies are diverse, and the conclusions are often controversial. This review systematically discusses the effects of alcohol consumption, focusing on light to moderate alcohol consumption, obesity, lipid and glucose metabolism, and blood pressure.

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