24 June 2019 In Dementia

BACKGROUND: Alcohol use has been identified as a risk factor for dementia and cognitive decline. However, some patterns of drinking have been associated with beneficial effects.

METHODS AND RESULTS: To clarify the relationship between alcohol use and dementia, we conducted a scoping review based on a systematic search of systematic reviews published from January 2000 to October 2017 by using Medline, Embase, and PsycINFO. Overall, 28 systematic reviews were identified: 20 on the associations between the level of alcohol use and the incidence of cognitive impairment/dementia, six on the associations between dimensions of alcohol use and specific brain functions, and two on induced dementias. Although causality could not be established, light to moderate alcohol use in middle to late adulthood was associated with a decreased risk of cognitive impairment and dementia. Heavy alcohol use was associated with changes in brain structures, cognitive impairments, and an increased risk of all types of dementia.

CONCLUSION: Reducing heavy alcohol use may be an effective dementia prevention strategy.

03 June 2019 In Cancer

Alcohol consumption has been established to be a major factor in the development and progress of cancer. Genetic polymorphisms of alcohol-metabolism genes result in differences between individuals in exposure to acetaldehyde, leading to possible carcinogenic effects. Arg47His (rs1229984 G > A) in ADH1B have been frequently studied for its potential effect on carcinogenesis. However, the findings are as yet inconclusive. To gain a more precise estimate of this potential association, we conducted a meta-analysis including 66 studies from 64 articles with 31999 cases and 50964 controls. The pooled results indicated that ADH1B Arg47His polymorphism is significantly associated with the decreased risk of overall cancer (homozygous model, odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.49-0.77; heterozygous model, OR = 0.71, 95% CI = 0.60-0.84; recessive model, OR = 0.83, 95% CI = 0.76-0.91; dominant model, OR = 0.62, 95% CI = 0.53-0.72; and allele comparison, OR = 0.82, 95% CI = 0.75-0.89). Stratified analysis by cancer type and ethnicity showed that a decreased risk was associated with esophageal cancer and head and neck cancer amongst Asians. In conclusion, our meta-analysis suggested that ADH1B Arg47His polymorphism was significantly associated with decreased overall cancer risk. These findings need further validation in large multicenter investigations.

26 February 2019 In Drinking & Eating Patterns

Low-risk thresholds for alcohol use differ across various national guidelines. To assess the novel WHO risk drinking levels in light of alcohol-sensitive common laboratory tests, we analysed biomarkers of liver status, inflammation and lipid profiles from a population-based survey of individuals classified to abstainers and different WHO risk drinking levels defined in terms of mean alcohol consumption per day. The study included 22,327 participants aged 25-74 years from the National FINRISK Study. Data on alcohol use, health status, diet, body weight and lifestyle (smoking, coffee consumption and physical activity) were recorded from structured interviews. Alcohol data from self-reports covering the past 12 months were used to categorize the participants into subgroups of abstainers and WHO risk drinking categories representing low, moderate, high and very high risk drinkers. Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Alcohol risk category was roughly linearly related with the occurrence of elevated values for GGT, ALT and CRP. Alcohol drinking also significantly influenced the incidence of abnormalities in serum lipids. Significantly higher odds for abnormal GGT, ALT and altered lipid profiles remained in alcohol drinkers even after adjustment for age, waist circumference, physical inactivity, smoking and coffee consumption. A more systematic use of laboratory tests during treatment of individuals classified to WHO risk drinking categories may improve the assessment of alcohol-related health risks. Follow-ups of biomarker responses may also prove to be useful in health interventions aimed at reducing alcohol consumption.

26 February 2019 In Cancer

PURPOSE: Breast cancer (BC) risk prediction allows systematic identification of individuals at highest and lowest risk. We extend the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk model to incorporate the effects of polygenic risk scores (PRS) and other risk factors (RFs).

METHODS: BOADICEA incorporates the effects of truncating variants in BRCA1, BRCA2, PALB2, CHEK2, and ATM; a PRS based on 313 single-nucleotide polymorphisms (SNPs) explaining 20% of BC polygenic variance; a residual polygenic component accounting for other genetic/familial effects; known lifestyle/hormonal/reproductive RFs; and mammographic density, while allowing for missing information.

RESULTS: Among all factors considered, the predicted UK BC risk distribution is widest for the PRS, followed by mammographic density. The highest BC risk stratification is achieved when all genetic and lifestyle/hormonal/reproductive/anthropomorphic factors are considered jointly. With all factors, the predicted lifetime risks for women in the UK population vary from 2.8% for the 1st percentile to 30.6% for the 99th percentile, with 14.7% of women predicted to have a lifetime risk of >/=17-<30% (moderate risk according to National Institute for Health and Care Excellence [NICE] guidelines) and 1.1% a lifetime risk of >/=30% (high risk).

CONCLUSION: This comprehensive model should enable high levels of BC risk stratification in the general population and women with family history, and facilitate individualized, informed decision-making on prevention therapies and screening.

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