15 June 2022 In Cancer
We examined associations between sex-specific alcohol intake trajectories and alcohol-related cancer risk using data from 22 756 women and 15 701 men aged 40 to 69 years at baseline in the Melbourne Collaborative Cohort Study. Alcohol intake for 10-year periods from age 20 until the decade encompassing recruitment, calculated using recalled beverage-specific frequency and quantity, was used to estimate group-based sex-specific intake trajectories. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for primary invasive alcohol-related cancer (upper aerodigestive tract, breast, liver and colorectum). Three distinct alcohol intake trajectories for women (lifetime abstention, stable light, increasing moderate) and six for men (lifetime abstention, stable light, stable moderate, increasing heavy, early decreasing heavy, late decreasing heavy) were identified. 2303 incident alcohol-related cancers were diagnosed during 485 525 person-years in women and 789 during 303 218 person-years in men. For men, compared with lifetime abstention, heavy intake (mean >/= 60 g/day) at age 20 to 39 followed by either an early (from age 40 to 49) (early decreasing heavy; HR = 1.75, 95% CI: 1.25-2.44) or late decrease (from age 60 to 69) (late decreasing heavy; HR = 1.94, 95% CI: 1.28-2.93), and moderate intake (mean
28 April 2022 In Diabetes

AIMS/HYPOTHESIS: The aim of this study was to evaluate the prospective association between baseline and 9 year change in alcohol consumption and long-term risk of diabetes and whether these associations might be modified by sex and/or BMI.

METHODS: We conducted a prospective analysis of 12,042 Atherosclerosis Risk in Communities (ARIC) study participants without prevalent diabetes (55% women, 78% white, mean age 54 years). Alcohol consumption was assessed at visit 1 (1987-1989) and visit 4 (1996-1998). We used Cox models to estimate hazard ratios for diabetes risk by baseline drinking categories and change in alcohol consumption, stratified by sex and obesity status.

RESULTS: During a median follow-up of 21 years, there were 3795 incident cases of diabetes. Among women, consuming 8-14 drinks/week was associated with a significantly lower risk of diabetes (HR 0.75, 95% CI 0.58, 0.96) compared with current drinkers consuming ≤1 drink/week. Among men, consuming 8-14 drinks/week was associated with a borderline significant lower risk of diabetes (HR 0.84, 95% CI 0.70, 1.00) and consuming >14 drinks/week was associated with a significantly lower risk of diabetes (HR 0.81, 95% CI 0.67, 0.97) (p(interaction) < 0.01 for sex). For both sexes, among current drinkers, there was a significant decreasing trend in diabetes risk as the alcohol consumption increased. The association was modified by BMI (p(interaction) = 0.042 for women, p(interaction) < 0.001 for men). In women, the inverse association was only seen among overweight and obese participants. In men, the inverse association was more pronounced among obese participants. On average, drinking status did not change substantially over the 9 year period. For men with alcohol intake ≥7 drinks/week at baseline, decreasing alcohol intake was associated with higher risk of diabetes (HR per daily drink decrease 1.12, 95% CI 1.02, 1.23).

CONCLUSIONS/INTERPRETATION: In this community-based population, there was an inverse association between alcohol consumption and diabetes risk. The amount of the alcohol consumption associated with lower risk was different in women and men, and the association was more pronounced among participants with higher BMI.

28 April 2022 In Dementia
AIM: This study aimed to investigate the association between alcohol consumption and the risk of Alzheimer's disease (AD). METHODS: PubMed and Web of Science databases were systematically searched as of 1 September 2019. Relative risk and 95% CI were used to evaluate the association between alcohol consumption and AD risk. Subgroup analyses based on the type of alcohol, ethnicity, study design and sex were carried out. An alcohol dose-response meta-analysis was carried out. RESULTS: A total of 13 studies were included in the quantitative synthesis, and six were used in the dose-response meta-analysis. Compared with non-drinkers, individuals who drank had a lower risk of AD (relative risk 0.68, 95% CI 0.53-0.87; I(2) = 87.9%, P
22 March 2022 In Liver Disease

BACKGROUND & AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk.

METHODS: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (>/=80 g/day (men), >/=50 g/day (women), for >/=10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC).

RESULTS: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 +/- 0.06 vs. 0.61 +/- 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption.

CONCLUSIONS: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions.

LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

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