Long-term exposure to transportation noise and obesity: A pooled analysis of eleven Nordic cohorts.

Background: Available evidence suggests a link between exposure to transportation noise and an increased risk of obesity. We aimed to assess exposure-response functions for long-term residential exposure to road traffic, railway and aircraft noise, and markers of obesity. Methods: Our cross-sectional study is based on pooled data from 11 Nordic cohorts, including up to 162,639 individuals with either measured (69.2%) or self-reported obesity data. Residential exposure to transportation noise was estimated as a time-weighted average Lden 5 years before recruitment. Adjusted linear and logistic regression models were fitted to assess beta coefficients and odds ratios (OR) with 95% confidence intervals (CI) for body mass index, overweight, and obesity, as well as for waist circumference and central obesity. Furthermore, natural splines were fitted to assess the shape of the exposure-response functions. Results: For road traffic noise, the OR for obesity was 1.06 (95% CI = 1.03, 1.08) and for central obesity 1.03 (95% CI = 1.01, 1.05) per 10 dB Lden. Thresholds were observed at around 50-55 and 55-60 dB Lden, respectively, above which there was an approximate 10% risk increase per 10 dB Lden increment for both outcomes. However, linear associations only occurred in participants with measured obesity markers and were strongly influenced by the largest cohort. Similar risk estimates as for road traffic noise were found for railway noise, with no clear thresholds. For aircraft noise, results were uncertain due to the low number of exposed participants. Conclusion: Our results support an association between road traffic and railway noise and obesity.

Associations of plant-based foods, red and processed meat, and dairy with gut microbiome in Finnish adults.

PURPOSE: Population-based studies on the associations of plant-based foods, red meat or dairy with gut microbiome are scarce. We examined whether the consumption of plant-based foods (vegetables, potatoes, fruits, cereals), red and processed meat (RPM) or dairy (fermented milk, cheese, other dairy products) are related to gut microbiome in Finnish adults. METHODS: We utilized data from the National FINRISK/FINDIET 2002 Study (n = 1273, aged 25-64 years, 55% women). Diet was assessed with 48-hour dietary recalls. Gut microbiome was analyzed using shallow shotgun sequencing. We applied multivariate analyses with linear models and permutational ANOVAs adjusted for relevant confounders. RESULTS: Fruit consumption was positively (beta = 0.03, SE = 0.01, P = 0.04), while a dairy subgroup including milk, cream and ice-creams was inversely associated (beta=-0.03, SE 0.01, P = 0.02) with intra-individual gut microbiome diversity (alpha-diversity). Plant-based foods (R2 = 0.001, P = 0.03) and dairy (R2 = 0.002, P = 0.01) but not RPM (R2 = 0.001, P = 0.38) contributed to the compositional differences in gut microbiome (beta-diversity). Plant-based foods were associated with several butyrate producers/cellulolytic species including Roseburia hominis. RPM associations included an inverse association with R. hominis. Dairy was positively associated with several lactic producing/probiotic species including Lactobacillus delbrueckii and potentially opportunistic pathogens including Citrobacter freundii. Dairy, fermented milk, vegetables, and cereals were associated with specific microbial functions. CONCLUSION: Our results suggest a potential association between plant-based foods and dairy or their subgroups with microbial diversity measures. Furthermore, our findings indicated that all the food groups were associated with distinct overall microbial community compositions. Plant-based food consumption particularly was associated with a larger number of putative beneficial species.

Exploring tradeoffs among diet quality and environmental impacts in self-selected diets: a population-based study.

PURPOSE: Proposed sustainable diets often deviate dramatically from currently consumed diets, excluding or drastically reducing entire food groups. Moreover, their environmental sustainability tends to be measured only in terms of greenhouse gases emissions. The aim of this study was to overcome these limitations and identify a cluster of already adopted, relatively healthy diets with substantially lower environmental impacts than the average diet. We also aimed to estimate the reduction in multiple environmental impacts that could be achieved by shifting to this diet cluster and highlight possible tradeoffs among environmental impacts. METHODS: The diet clusters were identified by applying energy-adjusted multiple factor analysis and hierarchical clustering to the dietary data of the National FinHealth 2017 Study (n = 5125) harmonized with life cycle assessment data on food products from Agribalyse 3.0 and Agri-Footprint using nutrient intakes and global warming potential, land use, and eutrophication of marine and freshwater systems as the active variables. RESULTS: We identified five diet clusters, none of which had the highest overall diet quality and lowest impact for all four environmental indicators. One cluster, including twenty percent of the individuals in the sample was identified as a "best compromise" diet with the highest diet quality and the second lowest environmental impacts of all clusters, except for freshwater eutrophication. The cluster did not exclude any food groups, but included more fruits, vegetables, and fish and less of all other animal-source foods than average. Shifting to this cluster diet could raise diet quality while achieving significant reductions in most but not all environmental impacts. CONCLUSION: There are tradeoffs among the environmental impacts of diets. Thus, future dietary analyses should consider multiple sustainability indicators simultaneously. Cluster analysis is a useful tool to help design tailored, socio-culturally acceptable dietary transition paths towards high diet quality and lower environmental impact.

Dietary Fiber Intake and Risk of Advanced and Aggressive Forms of Prostate Cancer: A Pooled Analysis of 15 Prospective Cohort Studies.

BACKGROUND: Evidence of an association between dietary fiber intake and risk of advanced and aggressive forms of prostate cancer (PC) and PC mortality is limited. OBJECTIVE: The aim of this study was to examine associations between intakes of dietary fiber overall and by food source and risk of advanced and aggressive forms of PC. DESIGN: The study design was a pooled analysis of the primary data from 15 cohorts in 3 continents. Baseline dietary fiber intake was assessed using a validated food frequency questionnaire or diet history in each study. PARTICIPANTS/SETTING: There were 842 149 men followed for up to 9 to 22 years between 1985 and 2009 across studies. MAIN OUTCOME MEASURES: The primary outcome measures were advanced (stage T4, N1, or M1 or PC mortality), advanced restricted (excluded men with missing stage and those with localized PC who died of PC), and high-grade PC (Gleason score ≥8 or poorly differentiated/undifferentiated) and PC mortality. STATISTICAL ANALYSIS PERFORMED: Study-specific multivariable hazard ratios (MVHR) were calculated using Cox proportional hazards regression and pooled using random effects models. RESULTS: Intake of dietary fiber overall, from fruits, and from vegetables was not associated with risk of advanced (n = 4863), advanced restricted (n = 2978), or high-grade PC (n = 9673) or PC mortality (n = 3097). Dietary fiber intake from grains was inversely associated with advanced PC (comparing the highest vs lowest quintile, MVHR 0.84; 95% CI 0.76-0.93), advanced restricted PC (MVHR 0.85; 95% CI 0.74-0.97), and PC mortality (MVHR 0.78; 95% CI 0.68-0.89); statistically significant trends were noted for each of these associations (P ≤ .03), and a null association was observed for high-grade PC for the same comparison (MVHR 1.00; 95% CI 0.93-1.07). The comparable results were 1.06 (95% CI 1.01-1.10; P value, test for trend = .002) for localized PC (n = 35,199) and 1.05 (95% CI 0.99-1.11; P value, test for trend = .04) for low/intermediate grade PC (n = 34 366). CONCLUSIONS: Weak nonsignificant associations were observed between total dietary fiber intake and risk of advanced forms of PC, high-grade PC, and PC mortality. High dietary fiber intake from grains was associated with a modestly lower risk of advanced forms of PC and PC mortality.

Pairwise association of key lifestyle factors and risk of solid cancers - A prospective pooled multi-cohort register study.

Smoking, alcohol consumption, obesity, and physical inactivity are key lifestyle risk factors for cancer. Previously these have been mostly examined singly or combined as an index, assuming independent and equivalent effects to cancer risk. The aim of our study was to systematically examine the joint pairwise and interactive effects of these lifestyle factors on the risk of a first solid primary cancer in a multi-cohort prospective setting. We used pooled data from seven Finnish health survey studies during 1972-2015, with 197,551 participants diagnosed with 16,373 solid malignant primary tumors during follow-up. Incidence of any cancer was analyzed separately without and with lung cancers using Poisson regression with main and interaction effects of key lifestyle factors. When excluding lung cancer, the highest risk of any cancer in men was observed for smokers with a BMI of ≥25 kg/m2 (HR 1.36, 95 % CI 1.25-1.48) and in women for smokers consuming alcohol (HR 1.22, 1.14-1.30). No statistically significant interactions between any studied risk factor pairs were observed. When including lung cancer, the highest HRs among men were observed for smokers who consume alcohol (HR 1.72, 1.57-1.89) and among women for smokers who were physically inactive (HR 1.38, 1.27-1.49). Smoking combined with other lifestyle factors at any exposure level resulted in highest pairwise risks, both in men and women. These results highlight the importance of smoking prevention, but also the importance of preventing obesity and reducing alcohol consumption.

Helicobacter hepaticus and Helicobacter bilis in liver and biliary cancers from ATBC and PLCO.

BACKGROUND: Helicobacter species (spp.) have been detected in human bile and hepatobiliary tissue Helicobacter spp. promote gallstone formation and hepatobiliary tumors in laboratory studies, though it remains unclear whether Helicobacter spp. contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to Helicobacter (H.) hepaticus or H. bilis proteins was associated with the development of hepatobiliary cancers in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, and US-based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). METHODS: We included 62 biliary and 121 liver cancers, and 190 age-matched controls from ATBC and 74 biliary and 105 liver cancers, and 364 age- and sex-matched controls from PLCO. Seropositivity to 14 H. hepaticus and H. bilis antigens was measured using a multiplex assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major hepatobiliary cancer risk factors and Helicobacter pylori serostatus. RESULTS: Seropositivity to the H. bilis antigen, P167D, was associated with more than a twofold higher risk of liver cancer (OR: 2.38; 95% CI: 1.06, 5.36) and seropositivity to the H. hepaticus antigens HH0407 or HH1201, or H. bilis antigen, HRAG 01470 were associated with higher risk of biliary cancer (OR: 5.01; 95% CI: 1.53, 16.40; OR: 2.40; 95% CI: 1.00, 5.76; OR: 3.27; 95% CI: 1.14, 9.34, respectively) within PLCO. No associations for any of the H. hepaticus or H. bilis antigens were noted for liver or biliary cancers within ATBC. CONCLUSIONS: Further investigations in cohort studies should examine the role of Helicobacter spp. in the etiology of liver and biliary cancers.

Every tenth malignant solid tumor attributed to overweight and alcohol consumption: A population-based cohort study.

BACKGROUND: Recent studies have shown that some four in ten cancers are attributable to a few key risk factors. The aim of this study was to estimate cohort-based population attributable fractions (PAFs) in Finland for potentially modifiable cancer risk factors. METHODS: Data from eight health studies including 253,953 subjects with 29,802 incident malignant solid tumors were analysed using Bayesian multivariate regression model with multiplicative risk factor effects. We estimated the effects of smoking, excess body weight, alcohol consumption, physical activity, parity and education on cancer incidence and related PAFs by cancer site, accounting for competing mortality. RESULTS: PAF for all cancer sites and exposures combined was 34% (95% credible interval 29%-39%) in men and 24% (19%-28%) in women. In men, 23% (21%-27%) and in women 8% (6%-9%) of all cancers were attributed to smoking. PAF related to excess body weight was 4% (2%-6%) in men and 5% (2%-7%) in women, to alcohol 7% (3%-10%) in men and 4% (0%-7%) in women, and to excess body weight and alcohol combined 10% (6%-15%) in men and 9% (4%-13%) in women. CONCLUSION: Smoking was the most important factor contributing to cancer burden in Finnish men and women over the last 40 years. The contribution of excess body weight and alcohol consumption together outweighed the role of smoking in women. As the prevalence of overweight is expected to increase, more efficient public health measures supporting adherence to healthy weight are essential to reduce cancer burden.

Partial substitution of red meat or processed meat with plant-based foods and the risk of colorectal cancer.

OBJECTIVES: Shifting from animal-based to plant-based diets could reduce colorectal cancer (CRC) incidence. Currently, the impacts of these dietary shifts on CRC risk are ill-defined. Therefore, we examined partial substitutions of red or processed meat with whole grains, vegetables, fruits or a combination of these in relation to CRC risk in Finnish adults. METHODS: We pooled five Finnish cohorts, resulting in 43 788 participants aged ≥ 25 years (79% men). Diet was assessed by validated food frequency questionnaires at study enrolment. We modelled partial substitutions of red (100 g/week) or processed meat (50 g/week) with corresponding amounts of plant-based foods. Cohort-specific hazard ratios (HR) for CRC were calculated using Cox proportional hazards models and pooled together using random-effects models. Adjustments included age, sex, energy intake and other relevant confounders. RESULTS: During the median follow-up of 28.8 years, 1124 CRCs were diagnosed. We observed small risk reductions when red meat was substituted with vegetables (HR 0.97, 95% CI 0.95 - 0.99), fruits (0.97, 0.94 - 0.99), or whole grains, vegetables and fruits combined (0.97, 0.95 - 0.99). For processed meat, these substitutions yielded 1% risk reductions. Substituting red or processed meat with whole grains was associated with a decreased CRC risk only in participants with < median whole grain intake (0.92, 0.86 - 0.98; 0.96, 0.93 - 0.99, respectively; pinteraction=0.001). CONCLUSIONS: Even small, easily implemented substitutions of red or processed meat with whole grains, vegetables or fruits could lower CRC risk in a population with high meat consumption. These findings broaden our insight into dietary modifications that could foster CRC primary prevention.

Effects of partial replacement of red and processed meat with non-soya legumes on bone and mineral metabolism and amino acid intakes in BeanMan randomised clinical trial.

The transition towards more plant-based diets may pose risks for bone health such as low vitamin D and Ca intakes. Findings for the contribution of animal and plant proteins and their amino acids (AA) to bone health are contradictory. This 6-week clinical trial aimed to investigate whether partial replacement of red and processed meat (RPM) with non-soya legumes affects AA intakes and bone turnover and mineral metabolism in 102 healthy 20-65-year-old men. Participants were randomly assigned to diet groups controlled for RPM and legume intake (designed total protein intake (TPI) 18 E%): the meat group consumed 760 g RPM per week (25 % TPI) and the legume group consumed non-soya legume-based products (20 % TPI) and 200 g RPM per week, the upper limit of the Planetary Health Diet (5 % TPI). No differences in bone (bone-specific alkaline phosphatase; tartrate-resistant acid phosphatase 5b) or mineral metabolism (25-hydroxyvitamin D; parathyroid hormone; fibroblast growth factor 23; phosphate and Ca) markers or Ca and vitamin D intakes were observed between the groups (P > 0·05). Methionine and histidine intakes were higher in the meat group (P ≤ 0·042), whereas the legume group had higher intakes of arginine, asparagine and phenylalanine (P ≤ 0·013). Mean essential AA intakes in both groups met the requirements. Increasing the proportion of non-soya legumes by reducing the amount of RPM in the diet for 6 weeks did not compromise bone turnover and provided on average adequate amounts of AA in healthy men, indicating that this ecologically sustainable dietary change is safe and relatively easy to implement.

Whole grain intake, diet quality and risk factors of chronic diseases: results from a population-based study in Finnish adults.

OBJECTIVES: Better diet quality of whole grain consumers could contribute to the associations between whole grain intake and chronic disease risk factors. We examined whole grain intake in relation to diet quality and chronic disease risk factors (anthropometrics, blood pressure, cholesterol, triglycerides, C-reactive protein and glucose) and the role of diet quality in whole grains' associations with each risk factor. METHODS: Our data included 5094 Finnish adults who completed a validated food frequency questionnaire and participated in a health examination within the National FinHealth 2017 Study. We assessed diet quality by the modified Baltic Sea Diet Score. P trends were calculated across whole grain intake quintiles by linear regression analysis. Interactions were assessed by including an interaction term in the analyses. RESULTS: Higher whole grain intake was associated with slightly better diet quality compared with lower intakes in both sexes (P < 0.001). Whole grain intake was inversely associated with body mass index (P < 0.001), waist circumference (P < 0.001) and total cholesterol (P = 0.02) in men. Adjusting for medication use attenuated the inverse associations with diastolic blood pressure (P = 0.06) and HDL cholesterol (P = 0.14) in men. We observed no associations in women. Diet quality did not modify the associations between whole grain intake and chronic disease risk factors. CONCLUSIONS: Our results suggest that whole grain intake was associated with small improvements in the chronic disease risk factors in men, regardless of diet quality. The sex differences may arise from varying health associations of whole grains from different cereal sources.

Genome-Wide Gene-Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk.

BACKGROUND: High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene-environment (GxE) interaction analysis to identify genetic variants that may modify these associations. METHODS: A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan. RESULTS: Meta-analyses confirmed positive associations between increased consumption of red meat and processed meat with colorectal cancer risk [per quartile red meat OR = 1.30; 95% confidence interval (CI) = 1.21-1.41; processed meat OR = 1.40; 95% CI = 1.20-1.63]. Two significant genome-wide GxE interactions for red meat consumption were found. Joint GxE tests revealed the rs4871179 SNP in chromosome 8 (downstream of HAS2); greater than median of consumption ORs = 1.38 (95% CI = 1.29-1.46), 1.20 (95% CI = 1.12-1.27), and 1.07 (95% CI = 0.95-1.19) for CC, CG, and GG, respectively. The two-step EDGE method identified the rs35352860 SNP in chromosome 18 (SMAD7 intron); greater than median of consumption ORs = 1.18 (95% CI = 1.11-1.24), 1.35 (95% CI = 1.26-1.44), and 1.46 (95% CI = 1.26-1.69) for CC, CT, and TT, respectively. CONCLUSIONS: We propose two novel biomarkers that support the role of meat consumption with an increased risk of colorectal cancer. IMPACT: The reported GxE interactions may explain the increased risk of colorectal cancer in certain population subgroups.

Dietary inflammatory index in relation to salivary cytokine concentrations and periodontitis: A cross-sectional analysis.

AIM: To examine the associations of dietary inflammatory index (DII) with salivary cytokine concentrations and periodontitis after controlling for body mass index (BMI), socio-demographic factors and lifestyle. MATERIALS AND METHODS: Subgroups from two Finnish surveys, DILGOM 2007 and Health 2000, were included (total n = 727). The DII scores were calculated based on a food frequency questionnaire. Periodontal status was assessed with a cumulative risk score in DILGOM 2007 and by pocket depth measurement in Health 2000. From saliva, interleukin (IL)-1ß, IL-1 receptor antagonist, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α concentrations were measured. RESULTS: The DII scores did not differ between non-periodontitis and periodontitis participants in pairwise comparison. After adjusting for energy intake, periodontal status, BMI, age, education level, smoking habit and physical activity, DII was not associated with salivary cytokine concentrations. After adjusting for salivary cytokine levels and other confounding factors, DII was associated with periodontitis in the Health 2000 subgroup but not in the DILGOM 2007 subgroup. CONCLUSIONS: The current data support the evidence that diet is not associated with salivary cytokine levels but may be associated with periodontitis. The association observed between diet and periodontitis is related to factors other than diet-dependent inflammatory tendency in the oral cavity.

Associations of EAT-Lancet Planetary Health Diet or Finnish Nutrition Recommendations with changes in obesity measures: a follow-up study in adults.

Background: Knowledge on the association between the EAT-Lancet Planetary Health Diet (PHD) or the Finnish Nutrition recommendations (FNR) and anthropometric changes is scarce. Especially, the role of the overall diet quality, distinct from energy intake, on weight changes needs further examination. Objectives: To examine the association between diet quality and weight change indicators and to develop a dietary index based on the PHD adapted for the Finnish food culture. Methods: The study population consisted of participants of two Finnish population-based studies (n = 4,371, 56% of women, aged 30-74 years at baseline). Dietary habits at the baseline were assessed with a validated food frequency questionnaire including 128-130 food items. We developed a Planetary Health Diet Score (PHDS) (including 13 components) and updated the pre-existing Recommended Finnish Diet Score (uRFDS) (including nine components) with energy density values to measure overall diet quality. Weight, height, and waist circumference (WC), and the body mass index (BMI) were measured at the baseline and follow-up, and their percentual changes during a 7-year follow-up were calculated. Two-staged random effects linear regression was used to evaluate ß-estimates with 95% confidence intervals. Results: Adherence to both indices was relatively low (PHDS: mean 3.6 points (standard deviation [SD] 1.2) in the range of 0-13; uRFDS: mean 12.7 points (SD 3.9) in the range of 0-27). We did not find statistically significant associations between either of the dietary indices and anthropometric changes during the follow-up (PHDS, weight: ß -0.04 (95% CI -0.19, 0.11), BMI: ß 0.05 (-0.20, 0.10), WC: ß -0.08 (-0.22, 0.06); uRFDS, weight: ß 0.01 (-0.04, 0.06), BMI: ß 0.01 (-0.04, 0.06), WC: ß -0.02 (-0.07, 0.03)). Conclusion: No associations between overall diet quality and anthropometric changes were found, which may be at least partly explained by low adherence to the PHD and the FNR in the Finnish adult population.

The impacts of partial replacement of red and processed meat with legumes or cereals on protein and amino acid intakes: a modelling study in the Finnish adult population.

BACKGROUND: A shift towards more plant-based diets is considered healthy and environmentally sustainable but may cause a concern regarding protein and amino acid intakes. This modelling study aimed to assess the impacts of partial replacement of red and processed meat with legumes or cereals on the protein and indispensable amino acid intakes in the Finnish adult population. MATERIALS AND METHODS: We used the cross-sectional data of the National FinDiet 2017 Survey (two non-consecutive 24-h recalls, n = 1655, 47% men, aged 18-74 years). Six replacement scenarios were created in which the amount of red and processed meat exceeding 70 g/day (Finnish nutrition recommendation), or 30 g/day (EAT-Lancet recommendation) was replaced with the same amounts of legumes, cereals or their combination. Differences to the reference diet were evaluated based on non-overlapping 95% confidence intervals. Population shares (%) below estimated average requirements (EAR) were calculated using the usual intake modelling methodology (SPADE). RESULTS: The replacement scenarios decreased the protein and indispensable amino acid intakes depending on gender and age. At the 70-g level, decreases were observed only in men aged 18-64 years. At the 30-g level, decreases were observed in other gender and age groups except women aged 65-74 years. In the scenarios, the mean daily protein intake was 15-18% of total energy intake (E%) (reference 17-18 E%), and the proportions below the EAR were 7-10% in men and 8-10% in women aged 18-64 years (reference 5-7%) and 20-25% in men and 16-20% in women aged 65-74 years (reference 14-17%). For total indispensable amino acids, the proportions below the EAR were <5% in the reference diet and the scenarios. CONCLUSIONS: The mean daily protein intake remained sufficient when red and processed meat was partially replaced with legumes or cereals in the Finnish adult population. However, protein adequacy in the elderly population warrants attention and more research.

This modelling study supports global efforts towards more plant-based diets, essential to human and planetary health, by providing insight into the impacts of partial replacement of red and processed meat with legumes or cereals on protein and indispensable amino acid intakes in the Finnish adult population.In general, the mean daily protein and indispensable amino acid intakes decreased but remained sufficient also when substantial amounts of red and processed meat were replaced with legumes or cereals.Some elderly men and women, however, had protein intake below the estimated average requirement, which needs to be considered particularly in the transition towards more plant-based and sustainable diets.

Waist-hip ratio is superior to BMI in predicting liver-related outcomes and synergizes with harmful alcohol use.

BACKGROUND: Obesity is associated with liver disease, but the best obesity-related predictor remains undefined. Controversy exists regarding possible synergism between obesity and alcohol use for liver-related outcomes (LRO). We assessed the predictive performance for LROs, and synergism with alcohol use, of abdominal obesity (waist-hip ratio, WHR), and compared it to overall obesity (body mass index, BMI). METHODS: Forty-thousand nine-hundred twenty-two adults attending the Finnish health-examination surveys, FINRISK 1992-2012 and Health 2000 studies, were followed through linkage with electronic healthcare registries for LROs (hospitalizations, cancers, and deaths). Predictive performance of obesity measures (WHR, waist circumference [WC], and BMI) were assessed by Fine-Gray models and time-dependent area-under-the-curve (AUC). RESULTS: There are 355 LROs during a median follow-up of 12.9 years (509047.8 person-years). WHR and WC emerge as more powerful predictors of LROs than BMI. WHR shows significantly better 10-year AUC values for LROs (0.714, 95% CI 0.685-0.743) than WC (0.648, 95% CI 0.617-0.679) or BMI (0.550, 95% CI 0.514-0.585) both overall and separately among men and women. WHR is predictive also in BMI strata. Absolute 10-year risks of LROs are more dependent on WHR than BMI. Moreover, WHR shows a significant supra-additive interaction effect with harmful alcohol use for liver-related outcomes (excess 10-year cumulative incidence of 2.8% from the interaction), which is not seen between BMI and harmful alcohol use. CONCLUSIONS: WHR is a better predictor than BMI or WC for LROs, and WHR better reflects the synergism with harmful alcohol use. WHR should be included in clinical assessment when evaluating obesity-related risks for liver outcomes.

Obesity has been linked to liver disease, but the most accurate measure for predicting obesity-related liver disease outcomes remains uncertain. In this study, we analyzed data from over 40,000 adults to compare the extent to which different measures of obesity can predict liver-related outcomes, such as severe liver disease, liver failure, or death from liver disease. The measures of obesity were the ratio of waist circumference to hip circumference (waist-hip ratio, WHR), waist circumference (WC), and body mass index (BMI). Our findings reveal that WHR and WC are stronger predictors of these outcomes than BMI. In particular, WHR demonstrated superior predictive ability and this predictive ability was influenced by harmful alcohol use. This study suggests that WHR may be a relatively simple but useful measure for clinicians to use when predicting obesity-related risks for liver health.

Genome-wide interaction analysis of folate for colorectal cancer risk.

BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. OBJECTIVES: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Mitochondrial DNA Fragmentation and Risk of Non-Hodgkin Lymphoma.

Importance: Research suggests that increased mitochondrial DNA copy number (mtDNAcn) is associated with increased risk of non-Hodgkin lymphoma (NHL); however, no studies to date have evaluated whether the mitochondrial DNA fraction with breaks (mtDNAfb) is associated with risk of NHL. Objective: To evaluate the association of mtDNAfb with NHL risk. Design, Setting, and Participants: This nested case-control study, which used prospectively collected samples as part of baseline enrollment (from 1985 through 1988) of 29 133 men who smoked for the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study conducted in southwest Finland, included 107 incident NHL cases and 107 controls (matched on date of birth ±5 years). Analyses were conducted from January to September 2022. Exposure: High-throughput real-time polymerase chain reaction assays quantifying mtDNAfb. Main Outcomes and Measures: Incident NHL cases were identified in the ATBC Study through April 30, 2002, using the Finnish Cancer Registry and the Register of Causes of Death. The mtDNAfb was quantified and categorized based on the median, tertile, and quartile distributions among controls. Odds ratios (ORs) and 95% CIs were estimated using conditional logistic regression models to assess the associations between categorized mtDNAfb and future risk of NHL, controlling for age, body mass index, number of cigarettes smoked per day, number of pack-years, and mtDNAcn. Results: A total of 29 133 men (median [IQR] age, 57.2 [52.6-62.5] years) participated in ATBC Study. Higher mtDNAfb was associated with an increased risk of NHL (median OR, 2.89; 95% CI, 1.40-5.93) in a dose-dependent manner (quartile 2 vs 1 OR, 1.24; 95% CI, 0.43-3.40; quartile 3 vs 1 OR, 3.58; 95% CI, 1.39-9.24; quartile 4 vs 1 OR, 3.42; 95% CI, 1.30- 8.99; P = .004 for trend). Conclusions and Relevance: This study's findings suggest that increased mtDNAfb is associated with an increased future risk of NHL. Additional studies are needed to confirm these findings, particularly among women and nonsmokers.

Associations of food motives with red meat and legume consumption in the population-based DILGOM study.

PURPOSE: To improve human health and environmental sustainability, red meat consumption should decrease and legume consumption increase in diets. More information on food motives, however, is required when developing more tailored and effective interventions targeting legume and meat consumption. We aimed to examine the associations between food motives and red meat and legume consumption, and whether these associations differ between different subgroups (gender, age groups, marital status, education, BMI). METHODS: Ten food motives (health, mood, convenience, sensory appeal, natural content, price-cheap, price-value, weight control, familiarity and ethical concern measured with Food Choice Questionnaire) were studied in 3079 Finnish adults in the population-based DILGOM study. Food consumption was assessed with Food Frequency Questionnaire. The adjusted estimates from multivariable regression models are reported. RESULTS: Higher relative importance of natural content (ß = - 0.275, 95% CI - 0.388; - 0.162) and ethical concern (ß = - 0.462, 95% CI - 0.620; - 0.305) were associated with lower red meat consumption, and higher appreciation of sensory appeal (ß = 0.482, 95% CI 0.347; 0.616) and price-cheap (ß = 0.190, 95% CI 0.099; 0.281) with higher red meat consumption. Higher importance of health (ß = 0.608, 95% CI 0.390; 0.825) was associated with higher legume consumption, and higher appreciation of convenience (ß = - 0.401, 95% CI - 0.522; - 0.279), price-value (ß = - 0.257, 95% CI - 0.380; - 0.133) and familiarity (ß = - 0.278, 95% CI - 0.393; - 0.164) with lower legume consumption. The associations of particularly ethical concern, weight control, sensory appeal and mood varied according to gender, age, marital status or BMI. CONCLUSION: The development and implementation of actions to decrease red meat and increase legume consumption should focus on several food motives across different subgroups.