Association Of Alcohol Intake Research Articles

Associations of alcohol intake with gut microbiome: a prospective study in a predominantly low-income Black/African American population

BackgroundAlcohol intake can the alter gut microbiome, which may subsequently affect human health. However, limited population-based, prospective studies have investigated associations of habitual and recent alcohol intake with the gut microbiome, particularly among Black/African American individuals. MethodsWe investigated the dose- and type-specific associations of habitual and recent alcohol intake with the gut microbiome among 538 Black/African American adults (150 males and 388 females). Habitual and recent alcohol intakes were assessed at cohort baseline (2002–2009) and stool collection (2018–2021), respectively. Gut microbiome was profiled using shotgun metagenomic sequencing. Generalized linear models were employed to evaluate the associations between alcohol intakes and gut microbiome composition, with adjustments for sociodemographic characteristics, other lifestyle factors, and comorbidities. FDR <0.1 was considered statistically significant. ResultsThe mean age at enrollment was 53.2 ± 7.7 years, with a mean interval of 13.8 years (range: 9.0-18.1 years) between baseline and stool sample collection. Recent alcohol intake was not significantly associated with microbial taxa abundance. However, habitual alcohol intake, both total amount and types of alcoholic beverages, showed significant associations with several microbial taxa abundance, primarily in males, including species within classes Clostridia, Bacilli, and Mahellia within Firmicutes. Specifically, total alcohol, beer, and red wine intakes were all inversely associated with genus MGYG-HGUT-02719 within class Clostridia (β=-2.26 to -0.09 per 1 drink/day increase). Red wine consumption was also inversely associated with the abundance of genera CAG-110, Oscillibacter, and Gemmiger within class Clostridia (β=-3.88 to -2.69), while positively associated with genus Absiella (β=1.81) within class Bacilli. Most of these associations remained significant after additionally adjusting for BMI and baseline comorbidities. ConclusionsWe identified gut microbial taxa associated with habitual alcohol intake among Black/African American males, although the magnitudes of these associations were generally small. Further research is needed to determine if these bacteria modify alcohol-disease relationships.

Alcohol Intake and Prevalent Kidney Stone: The National Health and Nutrition Examination Survey 2007-2018.

The association of alcohol intake with kidney stone disease (KSD) is not clear based on current clinical evidence. We examined the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and used logistic regression analyses to determine the independent association between alcohol intake and prevalent KSD. In total, 29,684 participants were eligible for the final analysis, including 2840 prevalent stone formers (SFs). The mean alcohol intake was 37.0 ± 2.4 g/day among SFs compared to 42.7 ± 0.9 among non-SFs (p = 0.04). Beer [odds ratio (OR) = 0.76, 95% CI: 0.61-0.94, p = 0.01] and wine (OR = 0.75, 95% CI: 0.59-0.96, p = 0.03) intakes were strongly associated with lower odds of prevalent KSD, while liquor intake had no association. Furthermore, the effects of beer and wine intakes on stone formation were dose-dependent. The OR for comparing participants drinking 1-14 g/day of beer to non-drinkers was 1.41 (95%CI: 0.97-2.05, p = 0.07), that of >14-≤28 g/day of beer to non-drinkers was 0.65 (95% CI: 0.42-1.00, p = 0.05), that of >28-≤56 g/day of beer to non-drinkers was 0.60 (95% CI: 0.39-0.93, p = 0.02), and that of >56 g/day of beer to non-drinkers was 0.34 (95% CI: 0.20-0.57, p < 0.001). Interestingly, the effect of wine intake was only significant among participants drinking moderate amounts (>14-28 g/day), with an OR of 0.54 (95% CI: 0.36-0.81, p = 0.003) compared to non-drinkers, but this effect was lost when comparing low-level (1-14 g/day) and heavy (>28 g/day) wine drinkers to non-drinkers. These effects were consistent in spline models. This study suggests that both moderate to heavy beer intake and moderate wine intake are associated with a reduced risk of KSD. Future prospective studies are needed to clarify the causal relationship.

Genetic influences on alcohol flushing in East Asian populations

BackgroundAlthough it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited.MethodsWe performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake.ResultsWe identified variants in the region of ALDH2 strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (ADH1B) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (ALDH2-rs671 and ADH1B-rs1229984), which need to be confirmed in larger studies. The estimated SNP-heritability on the liability scale was 13% (S.E. = 4%) for flushing, but the heritability estimate decreased to 6% (S.E. = 4%) when the effects of the lead variants were controlled for. Genetic instrumentation of higher alcohol intake using these variants recapitulated known associations of alcohol intake with hypertension. Using self-reported alcohol flushing as an instrument gave a similar association pattern of higher alcohol intake and cardiovascular disease-related traits (e.g. stroke).ConclusionThis study confirms that ALDH2-rs671 and ADH1B-rs1229984 are associated with alcohol flushing in East Asian populations. Our findings also suggest that self-reported alcohol flushing can be used as an instrumental variable in future studies of alcohol consumption.

Alcohol consumption and cancer incidence in women: interaction with smoking, body mass index and menopausal hormone therapy

BackgroundAlcohol consumption has been associated with increased risks of certain site-specific cancers and decreased risks of some other cancers. There is, however, little reliable evidence as to whether the alcohol-associated risks for specific cancers are modified by smoking, body mass index (BMI) and menopausal hormone therapy (MHT) use.MethodsIn the prospective UK Million Women Study, 1,233,177 postmenopausal women without prior cancer, mean age 56 (SD 5) years, reported their alcohol consumption in median year 1998 (IQR 1998–1999), and were followed by record-linkage for incident cancer. 438,056 women who drank no alcohol or < 1 drink/week were excluded. Cox regression yielded adjusted relative risks (RRs) and 95% confidence intervals (CIs) for 21 cancers by alcohol amount; statistical significance of interactions with smoking, BMI and MHT use was assessed after allowing for multiple testing.ResultsIn 795,121 participants, mean consumption was 6.7 (SD 6.4) alcoholic drinks/week. During 17 (SD 5) years of follow-up, 140,203 incident cancers were recorded. There was strong evidence for a substantial association between alcohol intake and risk of upper aero-digestive cancers (oesophageal squamous cell carcinoma, oral cavity, pharynx and larynx; RR per 1 drink/day = 1.38 [95% CI 1.31–1.46]). There was also strong evidence for more moderate positive associations with breast, colorectal and pancreatic cancer (RRs per 1 drink/day = 1.12 [1.10–1.14], 1.10 [1.07–1.13], 1.08 [1.02–1.13] respectively), and moderate negative associations with thyroid cancer, non-Hodgkin’s lymphoma, renal cell carcinoma and multiple myeloma (RRs per 1 drink/day = 0.79 [0.70–0.89], 0.91 [0.86–0.95], 0.88 [0.83–0.94], 0.90 [0.84–0.97] respectively). Significant interactions between alcohol and smoking were seen for upper aero-digestive cancers (RRs per 1 drink/day = 1.66 [1.54–1.79], 1.23 [1.11–1.36], 1.12 [1.01–1.25] in current, past, and never smokers respectively). BMI and MHT did not significantly modify any alcohol-associated risks.ConclusionsThese findings provide robust evidence that greater alcohol intake, even within relatively moderate ranges, increases the risk of cancers of the aerodigestive tract, breast, colorectal and pancreatic cancer, and probably decreases the risk of thyroid cancer, non-Hodgkin’s lymphoma, renal cell carcinoma and multiple myeloma. Associations of alcohol intake with cancer risk were not modified by MHT use, adiposity or smoking, except in the case of upper aero-digestive cancers, where the alcohol-associated risk was largely confined to smokers.

Sex and Tumor-Site Differences in the Association of Alcohol Intake With the Risk of Early-Onset Colorectal Cancer.

Given the increasing incidence of early-onset colorectal cancer (CRC; diagnosed before age 50 years) worldwide, it is important to identify modifiable risk factors. We investigated whether alcohol consumption in the young population correlated with an increased early-onset CRC risk that differed by tumor location and sex. We investigated the association between average daily alcohol consumption and the risk of early-onset CRC among 5,666,576 individuals age 20-49 years using data from the Korean National Health Insurance Service (2009-2019). Alcohol consumption levels of nondrinker, light (reference), moderate, and heavy drinker were defined as 0, <10, 10 to <30, and ≥30 g/d for men and 0, <10, 10 to <20, and ≥20 g/d for women, respectively. Multivariate Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) with 95% CIs. We identified 8,314 incident early-onset CRC cases during the follow-up period. Moderate and heavy drinkers showed an increased risk of early-onset CRC compared with light drinkers (aHR, 1.09 [95% CI, 1.02 to 1.16] and aHR, 1.20 [95% CI, 1.11 to 1.29], respectively). Subgroup analysis by tumor location showed positive dose-response significance for early-onset distal colon and rectal cancers, but not for proximal colon cancer. The dose-response association between drinking frequency and risk of early-onset CRC was significant, with a 7%, 14%, and 27% increased risk for 1-2, 3-4, and ≥5 d/wk compared with nondrinkers, respectively. Excessive alcohol consumption increases the risk of CRC onset before age 50 years. Thus, effective interventions are required to discourage alcohol consumption among young people and to tailor CRC screening approaches for high-risk individuals.

PS-BPC12-1: AGE-RELATED DIFFERENCES IN LONGITUDINAL ASSOCIATIONS BETWEEN ALCOHOL INTAKE AND ARTERIAL STIFFNESS, PRESSURE WAVE REFLECTION, AND INFLAMMATION IN MALE EMPLOYEES

Backgrounds: The effect of alcohol intake on arterial stiffness related to macro-vascular damage, pressure wave reflection related to both macro- and micro- vascular damages and inflammation have not been fully concluded. Aims: In the present longitudinal observational study, which conducted in annually repeated measurements data, mixed model analyses were applied to examine the difference of longitudinal associations of amount of alcohol intake (i.e., non, mild, moderate and heavy) with arterial stiffness, pressure wave reflection and inflammation. Methods: In 4016 middle-aged (43 ± 9 years) healthy Japanese men without cardiovascular disease (CVD) at the study baseline, alcohol intake, which obtained by questionnaire, risk factors for CVD, brachial-ankle pulse wave velocity (brachial-ankle PWV), radial augmentation index (rAI), and serum C-reactive protein levels (CRP) were measured annually during a 9-year study period. Results: In this repeated measurements data, mix model linear regression analyses demonstrated that alcohol intake had a significant longitudinal association with brachial-ankle PWV and rAI in dose-dependent manner {i.e., non, Mild (1–10 g/day), Moderate (10–30 g/day) and heavy (Over 30 g/day) ethanol intake} (Figure). When baPWV was included as a covariate, the association of alcohol intake with rAI was significant. On the other hand, the serum CRP levels were significantly lower in mild to moderate alcohol intake groups as compared to other groups (i.e., U-shaped) (Figure). Conclusion: The amount of alcohol intake may have longitudinal linear association with increased arterial stiffness and abnormal pressure wave reflection, but it may have a U-shaped relationship with inflammation reflected by serum CRP levels. Thus, the alcohol intake may longitudinally affect both macro- and micro- vascular damages in a linear dose-dependent manner without mediating inflammation.

Utility of Continuous Disease Subtyping Systems for Improved Evaluation of Etiologic Heterogeneity.

Simple SummaryThis paper presents an extended version of the Cox regression model to examine heterogeneous effects of risk factors on disease subtypes defined by a continuous biomarker. This approach can be easily applied to cancer studies and is accessible to researchers via user-friendly R scripts.Molecular pathologic diagnosis is important in clinical (oncology) practice. Integration of molecular pathology into epidemiological methods (i.e., molecular pathological epidemiology) allows for investigating the distinct etiology of disease subtypes based on biomarker analyses, thereby contributing to precision medicine and prevention. However, existing approaches for investigating etiological heterogeneity deal with categorical subtypes. We aimed to fully leverage continuous measures available in most biomarker readouts (gene/protein expression levels, signaling pathway activation, immune cell counts, microbiome/microbial abundance in tumor microenvironment, etc.). We present a cause-specific Cox proportional hazards regression model for evaluating how the exposure–disease subtype association changes across continuous subtyping biomarker levels. Utilizing two longitudinal observational prospective cohort studies, we investigated how the association of alcohol intake (a risk factor) with colorectal cancer incidence differed across the continuous values of tumor epigenetic DNA methylation at long interspersed nucleotide element-1 (LINE-1). The heterogeneous alcohol effect was modeled using different functions of the LINE-1 marker to demonstrate the method’s flexibility. This real-world proof-of-principle computational application demonstrates how the new method enables visualizing the trend of the exposure effect over continuous marker levels. The utilization of continuous biomarker data without categorization for investigating etiological heterogeneity can advance our understanding of biological and pathogenic mechanisms.

Association of alcohol intake and female gender with high expression of TMPRSS2 in tongue as potential risk for SARS-CoV-2 infection.

COVID-19 is pandemic since 2020 and further information is necessary on the risk factors associated with the infection of SARS-CoV-2. As an entry mechanism, SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as receptor and transmembrane serine protease 2 (TMPRSS2) to activate fusion with host plasma membrane. Because dysgeusia is an early symptom of COVID-19, we here studied the expression of ACE2 and TMPRSS2 in the tongue and the associated tissues of mice and humans with immunohistochemistry and immunoblot analysis. ACE2 expression was low in the human tongue but was observed in the squamous epithelium, perineurium, arterial wall, salivary glands as well as taste buds. In contrast, mice showed high expression. In sharp contrast, TMPRSS2 expression was high in all the cells mentioned above in humans but relatively low in mice except for salivary glands. We then performed semi-quantitation of immunohistochemistry data of human ACE2 and TMPRSS2 and analyzed for age, sex, alcohol intake, and smoking habit with logistic regression analysis. We found that alcohol intake and female gender were the significant risk factors for increasing TMPRSS2 expression. In conclusion, TMPRSS2 is an important factor to be considered regarding SARS-CoV-2 entry and amplification in the oral cavity, which is promoted through drinking habit.

Understanding the effect of smoking and drinking behavior on Parkinson's disease risk: a Mendelian randomization study

Previous observational studies have identified correlations between Parkinson’s disease (PD) risk and lifestyle factors. However, whether or not those associations are causal remains unclear. To infer causality between PD risk and smoking or alcohol intake, we conducted a two-sample Mendelian randomization study using genome-wide association study summary statistics from the GWAS & Sequencing Consortium of Alcohol and Nicotine use study (1.2 million participants) and the latest meta-analysis from the International Parkinson’s Disease Genomics Consortium (37,688 PD cases and 18,618 proxy-cases). We performed sensitivity analyses, including testing for pleiotropy with MR-Egger and MR-PRESSO, and multivariable MR modeling to account for the genetic effects of competing substance use traits on PD risk. Our results revealed causal associations of alcohol intake (OR 0.79; 95% CI 0.65–0.96; p = 0.021) and smoking continuation (which compares current vs. former smokers) (OR 0.64; 95% CI 0.46–0.89; p = 0.008) with lower PD risk. Multivariable MR analyses showed that the causal association between drinks per week and PD is unlikely due to confounding by smoking behavior. Finally, frailty analyses suggested that the causal effects of both alcohol intake and smoking continuation on PD risk estimated from MR analysis are not explained by the presence of survival bias alone. Our findings support the role of smoking as a protective factor against PD, but only when comparing current vs. former smokers. Similarly, increased alcohol intake had a protective effect over PD risk, with the alcohol dehydrogenase 1B (ADH1B) locus as a potential candidate for further investigation of the mechanisms underlying this association.

Highlights From the Circulation Family of Journals.

This month's highlights from the subspecialty journals cover atrial fibrillation, microvascular dysfunction, progression of atherosclerosis, a stroke quality initiative, and a subanalysis of DAPAHF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure). Applying an artificial intelligence algorithm to sinus rhythm ECGs independently predicts atrial fibrillation in a study from Circulation: Arrhythmia and Electrophysiology. In Circulation: Genomic and Precision Medicine, the association of alcohol intake with atrial fibrillation was evaluated according to genetic predisposition to atrial fibrillation. In Circulation: Cardiovascular Interventions, a randomized trial of ranolazine treatment for microvascular dysfunction is reported. In Circulation: Cardiovascular Imaging, baseline 18F-sodium florid activity by positron emission tomography was associated with incident coronary calcification. The Target: Stroke quality initiative from the American Heart Association is reported in Circulation: Cardiovascular Quality and Outcomes. A substudy in Circulation: Heart Failure evaluates the benefit of dapagliflozin across cohorts of duration of heart failure from DAPA-HF.

Association of Alcohol Intake and Semen Parameters in Men With Primary and Secondary Infertility: A Cross-Sectional Study.

Alcohol consumption has commonly been associated with semen parameters. However, the association between alcohol intake and semen parameters in primary and secondary infertile men remains unclear. In this study, 776 infertile men from China were grouped according to alcohol intake: abstainers, moderate drinkers (<9 units/week, up to approximately 100 g of ethanol) and heavy drinkers (≥9 units/week). Semen parameters, including semen volume, sperm concentration, total sperm count, progressive motility and normal morphology were investigated. Alcohol consumption and other lifestyle factors were assessed by questionnaire. Logistic regression models were applied. There was no significant association between alcohol consumption and semen parameters in men with primary infertility. Smaller testis volumes and lower sperm concentrations were found among moderate and heavy drinkers in the secondary infertility group than among abstainers. After adjustment for potential confounders, men with secondary infertility and heavy alcohol consumption had a higher risk of abnormal sperm concentrations (OR = 3.72; 95% CI, 1.04, 13.37). These findings suggest that alcohol intake may decrease sperm concentrations in men with secondary infertility, whereas no association was found in men with primary infertility. It may be beneficial for clinicians to advise male patients with secondary infertility who are seeking fertility treatment to avoid heavy alcohol consumption.

Multimodal brain-age prediction and cardiovascular risk: The Whitehall II MRI sub-study

Brain age is becoming a widely applied imaging-based biomarker of neural aging and potential proxy for brain integrity and health. We estimated multimodal and modality-specific brain age in the Whitehall II (WHII) MRI cohort using machine learning and imaging-derived measures of gray matter (GM) morphology, white matter microstructure (WM), and resting state functional connectivity (FC). The results showed that the prediction accuracy improved when multiple imaging modalities were included in the model (R2 = 0.30, 95% CI [0.24, 0.36]). The modality-specific GM and WM models showed similar performance (R2 = 0.22 [0.16, 0.27] and R2 = 0.24 [0.18, 0.30], respectively), while the FC model showed the lowest prediction accuracy (R2 = 0.002 [-0.005, 0.008]), indicating that the FC features were less related to chronological age compared to structural measures. Follow-up analyses showed that FC predictions were similarly low in a matched sub-sample from UK Biobank, and although FC predictions were consistently lower than GM predictions, the accuracy improved with increasing sample size and age range. Cardiovascular risk factors, including high blood pressure, alcohol intake, and stroke risk score, were each associated with brain aging in the WHII cohort. Blood pressure showed a stronger association with white matter compared to gray matter, while no differences in the associations of alcohol intake and stroke risk with these modalities were observed. In conclusion, machine-learning based brain age prediction can reduce the dimensionality of neuroimaging data to provide meaningful biomarkers of individual brain aging. However, model performance depends on study-specific characteristics including sample size and age range, which may cause discrepancies in findings across studies.

Association of alcohol intake with incidence and progression of diabetic retinopathy

PurposeWe examined the longitudinal association of baseline alcohol intake and frequency with the 6-year incidence and progression of diabetic retinopathy (DR) in a population-based cohort of Singaporean Indians.MethodsWe included 656...

Abstract P420: Alcohol Consumption and Longitudinal Changes in Magnetic Resonance Imaging-defined Brain Abnormalities: The Cardiovascular Health Study

Introduction: Alcohol intake has been related with a complex group of associations with brain structure in cross-sectional analyses, but to our knowledge, its prospective relationship with structural brain abnormalities detected by MRI has never been reported. Hypothesis: We hypothesized that consumers of 1-&lt;7 drinks/week would have slower progression of leukoaraiosis (white matter abnormalities) but more rapid progression of brain atrophy than longer-term abstainers. Methods: As part of the Cardiovascular Health Study, 1 996 adults aged ≥65 years underwent MRI scanning in 1991-94 and again in 1997-99, having excluded 120 participants with a history of cerebrovascular disease before the initial scan. Alcohol consumption was assessed at each annual visit by self-reported intake of wine, beer and liquor. A 10-point white matter grade (WMG) and ventricular grade (VG) were assessed in a standardized and blinded manner in both scans; hippocampal and total brain volumes were also quantified on the second scan. We estimated the associations of alcohol intake in categories (as reported closest to the date of initial scan), with MRI findings at follow-up with multinomial ordered logistic regression (WMG ≤ 3 ref and ≥ 4; VG ≤ 3 ref , =4 and ≥5) using inverse probability weighting to account for attrition. Results: We observed a U-shaped association with WMG, with significantly lower risk among participants consuming 1-&lt;7 drinks/week (OR 0.38; 95% CI 0.17-0.82, table) than long-term abstainers (P quadtrend = 0.01). For VG, the association was inverse (P trend = 0.06), with significantly less progression among drinkers of 1-&lt;7 drinks/week than long-term abstainers (OR 0.62; 95% CI 0.40-0.97). We identified no significant associations of alcohol intake with quantitative mean hippocampal or total brain volumes at the second scan. Conclusions: Compared with long-term abstention, consumption of 1-&lt;7 drinks/week of alcohol was generally associated with less progression of leukoaraiosis and some measures of brain atrophy in older adults.

Association of Alcohol intake with Pulmonary Tuberculosis: A Case Control Study

Association of Alcohol intake with Pulmonary Tuberculosis: A Case Control Study

Alcohol Consumption and Risk of Dementia and Cognitive Decline Among Older Adults With or Without Mild Cognitive Impairment

Substantial heterogeneity and uncertainty exist in the observed associations between alcohol consumption and dementia. To assess the association between alcohol consumption and dementia and the roles of mild cognitive impairment (MCI) and apolipoprotein E ε4 (APOE E4) genotype in modifying this association. This cohort study used data from the Ginkgo Evaluation of Memory Study, conducted from 2000 to 2008 among US community-dwelling participants. This study analyzed 3021 participants aged 72 years and older who were free of dementia. Data analysis was performed from 2017 to 2018. Self-reported alcohol consumption, drinking frequency, and quantity. Using multivariable proportional hazards regression and linear mixed models, the risk of dementia and the rate of change over time in the Modified Mini-Mental State Examination were estimated. Among 3021 participants, the median (interquartile range) age was 78 (76-80) years; 1395 (46.2%) were female. During a median (interquartile range) follow-up of 6.0 (4.9-6.5) years, 512 cases of dementia occurred. For 7.1 to 14.0 drinks per week compared with less than 1.0 drink per week, the hazard ratios for dementia were 0.63 (95% CI, 0.38-1.06) among 2548 participants without MCI and 0.93 (95% CI, 0.47-1.84) among 473 participants with MCI. Among participants with MCI, the hazard ratio for dementia was 1.72 (95% CI, 0.87-3.40) for more than 14.0 drinks per week compared with less than 1.0 drink per week. The association of alcohol intake with dementia differed for participants with and without baseline MCI (P for interaction = .03). Among participants without MCI, daily low-quantity drinking was associated with lower dementia risk than infrequent higher-quantity drinking (hazard ratio, 0.45; 95% CI, 0.23-0.89; P = .02). Findings were consistent when stratified by sex, age, and APOE E4 genotype. Compared with drinking less than 1.0 drink per week, complete abstention (in participants without MCI) and the consumption of more than 14.0 drinks per week (in participants with MCI) were associated with lower Modified Mini-Mental State Examination scores (mean difference at follow-up compared with baseline, -0.46 point [95% CI, -0.87 to -0.04 point] and -3.51 points [95% CI, -5.75 to -1.27 points], respectively). In this study, complete abstention and consuming more than 14.0 drinks per week (compared with drinking <1.0 drink per week) were associated with lower cognitive scores among participants aged 72 years and older. Particular caution is needed among individuals with MCI who continue to drink alcohol.

Non-linear (J-shaped) association of alcohol intake with total mortality: Results from the MORGAM project

Non-linear (J-shaped) association of alcohol intake with total mortality: Results from the MORGAM project

Abstract P1-09-01: CD8+ T-cell gene expression and signatures in breast cancer and adjacent normal breast tissue: Association with body mass index, alcohol intake, and age at diagnosis

Abstract Background: Our understanding of mediators of immune infiltration in breast cancer and normal breast tissue remains limited. We hypothesize that patient factors known to be associated with inflammation and immune subsets, including body mass index, alcohol intake, and age and diagnosis, may play an important role in the tumor-immune microenvironment. Analyses of immune gene expression and signatures facilitate interrogation of the immune microenvironment in large patient cohorts. Methods: Participants from the Nurses' Health Study cohorts I and II diagnosed with invasive breast cancer were included. Total RNA extracted and microarray performed for 882 tumor and 695 tumor-adjacent samples, of which 623 tumors have matched tumor-adjacent data. CD8+ T-cell expression metrics were assessed: CD8A single gene expression (CD8Agene), a CD8 T-cell signature (CD8sig), and a tumor infiltrating lymphocyte signature derived from the GeparSixto clinical trial (GSAct). Standard clinicopathologic features were evaluated, as well as body mass index (BMI) one year prior to diagnosis, cumulative average alcohol intake, and age at diagnosis. Results: Overall, tumor and adjacent normal tissue demonstrated positive correlation of CD8Agene, CD8sig, and GSAct (n=623 pairs, Pearson's r = 0.46, 0.36, 0.31, respectively; all p&amp;lt;0.001). Similar correlations were present in TCGA breast cancer, an independent cohort (n=112 pairs, Pearson's r = 0.34, 0.17, 0.45, respectively; all p&amp;lt;0.001). We evaluated paired tumor and adjacent normal samples within individual immunohistochemical (IHC) subtype or PAM50 subtype by Wilcoxon signed-rank test. There was not a consistent trend for CD8Agene, CD8sig, nor GSAct to be greater in tumor or normal within subtypes. We then evaluated patient features/exposures and tumor immune expression metrics. For tumor-adjacent normal, there was no significant association of alcohol intake, BMI, or age at diagnosis with CD8 gene/expression metrics. For tumor tissue, a multivariate model demonstrated that BMI one year before diagnosis was significantly associated with CD8Agene expression. There was no significant association of alcohol intake or age at diagnosis with CD8 gene/expression metrics. We are currently evaluating the association of these CD8 T-cell gene expression signatures with CD8 T-cell immunohistochemistry in a subset of patients, which will be reported at the time of abstract presentation. Conclusion: In this cohort of over 600 tumor:normal pairs and a separate validation cohort, multiple distinct CD8+ T-cell expression metrics are correlated between breast cancer and tumor-adjacent normal breast tissue. This suggests that the adjacent normal breast may reflect an altered immune microenvironment in the context of breast cancer. While age at diagnosis and alcohol intake are not significantly associated with tumor CD8 expression metrics, BMI was significantly associated with tumor CD8Agene expression in a multivariate model. Citation Format: Damicis A, Heng YJ, Kensler K, Asad S, Adams E, Singh J, Zhang Y, Nock W, Wesolowski R, Williams N, Reinbolt R, Sardesai S, VanDeusen J, Noonan A, Lustberg MB, Ramaswamy B, Eliassen AH, Hankinson SE, Tamimi R, Stover DG. CD8+ T-cell gene expression and signatures in breast cancer and adjacent normal breast tissue: Association with body mass index, alcohol intake, and age at diagnosis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-01.

Abstract P227: Association of Alcohol Intake with Cardiovascular and Total Mortality

Introduction: Moderate alcohol intake is associated with reduced risk of ischemic heart disease and total mortality but might have a detrimental role in several other diseases (in particular some cancers). The association of moderate alcohol intake with reduced total mortality has therefore been questioned. Hypothesis: Alcohol intake have a non-linear association with cardiovascular (CV) and total mortality. Methods: Using harmonised data from the cohorts in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project, the association of alcohol intake with risk of cardiovascular disease and total mortality was assessed using multivariable Cox regression. Multiple imputation (n=10) was used to accommodate missing data for covariates. Results: 67.4% of the populations studied were drinkers (median intake among drinkers 11 g/day of ethanol, no missing data). Their mortality was observed over median follow-up of 13.8 yrs and covariates (age, sex, smoking, hypertension, diabetes, history of CVD, BMI and level of education) were available for 19 cohorts (1 from Australia and 18 from Europe), including 197,113 individuals (mean age 51±12 y, 60% men, no missing data) and 36,730 deaths (12,644 coronary or cerebrovascular). Former drinkers (2.8%) were excluded from the reference group, which thus comprised habitual teetotallers only (17.7%). Because of missing data, we failed to distinguish between teetotallers and former drinkers in n=24,036 (12.2%) non-drinkers; these individuals were analysed separately but not included in the reference group. In comparison with the reference group, intake of alcohol up to 5 g/day was associated with a 10.5% (95%CI: 6.7% to 14.2%) reduction in the risk of total mortality and 11.8% (5.2% to 17.9%) in the risk of CV mortality; intake between 5 and 10 g/day with a 6.5% (2.0% to 11.0%) and a 3.4% (0.3% to 15.5%) reduction, respectively, while intake over 20 g/day was associated with a 14.5% (9.6% to 19.7%) increase in risk of total mortality and a 6.3% (-1.5% to 14.7%) rise in the risk of CV mortality. Findings were similar in men and women and according to level of education, whereas they were heterogeneous across Countries, with greater protection by alcohol observed in Italy and France and lowest in Australia. The reduced risk of mortality associated with alcohol in moderation was more marked when the beverage of preference was wine rather than beer or spirits; the increased risk associated with heavy intake appeared in individuals whose beverage of preference was beer or spirits. Conclusions: Using a large multi Country cohort, we confirmed that intake of more than 2 alcoholic units per day is associated with a detrimental health effect, while intake of alcohol in moderation (up to 1 unit per day) is associated with reduced risk of CV and total mortality, with small variations according to Country and type of alcoholic beverage.

Influence of hiatal hernia and male sex on the relationship between alcohol intake and occurrence of Barrett's esophagus.

BackgroundThe association of alcohol intake with the incidence of Barrett’s esophagus (BE) has been inconsistent. Although hiatal hernia and male sex are well-known risk factors of BE, its effect on the association of alcohol intake with the incidence of BE remains unknown.AimTo investigate whether the influence of alcohol intake on the occurrence of BE might differ depending on male sex and presence of hiatal hernia.MethodsWe utilized a database of 8031 patients that underwent upper endoscopy for health screening in a prospective, multicenter, cohort study (the Upper Gastro Intestinal Disease study). The incidence of endoscopic columnar-lined esophagus (eCLE; endoscopically diagnosed BE) was the outcome variable. Multivariable logistic regression analysis was conducted to assess the association between alcohol intake and eCLE stratified by male sex and hiatal hernia, adjusting for clinical features and other potential confounders.ResultsAlcohol intake (≥20 g/day) showed a marginally significant association with the incidence of eCLE in participants without hiatal hernia (0 vs. ≥20 g/day; odds ratio [OR], 1.62; 95% confidence interval [CI], 0.92–2.85, P = 0.09) but not in participants with hiatal hernia (0 vs. ≥20/day; OR, 0.99; 95% CI, 0.59–1.65; P = 0.95). Furthermore, alcohol intake (≥20 g/day) was significantly associated with the incidence of eCLE in male participants without hiatal hernia (0 vs. ≥20 g/day; OR, 1.98; 95% CI, 1.04–4.03; P = 0.04) but not in female participants without hiatal hernia (0 vs. ≥20 g/day; OR, 0.47; 95% CI, 0.03–2.37; P = 0.42).ConclusionsThe effect of alcohol intake on the incidence of eCLE might be associated with hiatal hernia status and male sex.