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1.
Mol Nutr Food Res ; : e2001133, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33548087

RESUMO

SCOPE: A high fructose and galactose intake have shown adverse metabolic effects in animal models and in humans, but it is yet unknown if addition of fermentable dietary fiber could mitigate such effects. This study investigated the effects of high intakes of fructose and galactose, with/without added fructooligosaccharides (FOS), on metabolic factors, inflammation, and gut integrity markers in rats. METHODS AND RESULTS: Rats (n = 6/group) received different carbohydrates at isocaloric conditions for 12 wk as follows: 1)starch (control), 2)fructose, 3)galactose, 4)starch+FOS (FOS control), 5)fructose+FOS, and 6)galactose+FOS, together with a high amount of omega-6 fatty acids in all diets except for in 7)starch+olive oil (negative control). The rats fed the galactose and galactose+FOS diets exhibited lower body weight than other groups. High-galactose diets had more pronounced effects on metabolic factors and gut permeability than high-fructose diets. High-fructose diets showed less pronounced effect on these selected markers. No differences in inflammatory markers were detected for any of the diets. CONCLUSIONS: Our results suggest potential adverse effects of high galactose and fructose on metabolic factors and gut integrity markers, but not on inflammation. However, several mechanisms are at play, and general net effects were difficult to determine conclusively for the conditions tested. This article is protected by copyright. All rights reserved.

2.
Clin Nutr ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33610424

RESUMO

BACKGROUND AND AIMS: Each year, millions of people suffer from fragility fractures. Hip fractures are the most devastating type of such fractures. We aimed to investigate whether the association of dietary calcium intake with hip fracture risk can be modified by a healthy diet, herein defined as the modified Mediterranean diet score (mMED), in Swedish adults. METHODS: The study included 82,092 men and women at baseline. Diet and covariate data were collected twice, 12 years apart, using questionnaires. Information on incident hip fractures was collected from a national registry. Dietary calcium intake and mMED were each categorized into low, medium and high categories, and in nine combined strata of the two exposures. Multivariable adjusted hazard ratios (HR) of hip fracture with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression analysis, with time-updated information on exposures and covariates. Non-linear trends were assessed using restricted cubic splines. RESULTS: During 20 years of follow-up including 1,367,260 person-years at risk, 5938 individuals experienced a hip fracture. Dietary calcium intake and hip fracture were non-linearly associated, whereas adherence to mMED decreased hip fracture rates in a dose-response pattern. The lowest hip fracture rates were observed among women and men who reported a calcium intake of 800 mg or more, combined with a high adherence to mMED. In each stratum of calcium intake, the HRs of hip fracture were increasingly higher with lower adherence to mMED, compared with the reference level (high calcium and high mMED). Individuals with low calcium intake (<800 mg/day) or high calcium intake (>1200 mg/day) combined with low adherence to mMED had a HR of 1.54 (95% CI 1.28-1.85) and 1.50 (95% CI 1.26-1.77), respectively. No major differences in the hip fracture risk patterns were discerned between women and men. CONCLUSION: A moderate to high dietary calcium intake in the context of an overall healthy diet were associated with lower hip fracture rates.

3.
Sci Rep ; 11(1): 4296, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619316

RESUMO

A deeper understanding of the causal links from education level to health outcomes may shed a light for disease prevention. In the present Mendelian randomization study, we found that genetically higher education level was associated with lower risk of major mental disorders and most somatic diseases, independent of intelligence. Higher education level adjusted for intelligence was associated with lower risk of suicide attempts, insomnia, major depressive disorder, heart failure, stroke, coronary artery disease, lung cancer, breast cancer, type 2 diabetes and rheumatoid arthritis but with higher risk of obsessive-compulsive disorder, anorexia nervosa, anxiety, bipolar disorder and prostate cancer. Higher education level was associated with reduced obesity and smoking, which mediated quite an extent of the associations between education level and health outcomes. These findings emphasize the importance of education to reduce the burden of common diseases.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33462619

RESUMO

CONTEXT: The associations of circulating insulin-like growth factor-1 (IGF-1) levels with bone mineral density and fracture risk are inconclusive in observational studies. OBJECTIVE: We conducted a mendelian randomization study to assess the associations of serum IGF-1 levels with estimated bone mineral density (eBMD) and fracture. METHODS: Genetic instruments for IGF-1 were selected at the genome-wide significance level (P < 5 × 10-8) from a genome-wide association study including 358 072 individuals of European ancestry. Summary-level data for eBMD (426 824 individuals) and fracture (53 184 fracture cases and 373 611 noncases) were obtained from the UK Biobank study. Univariable and multivariable mendelian randomization analyses methods were used to estimate the associations of IGF-1 with eBMD and fracture. The main outcome measure included the change of eBMD and odds ratio of fracture per genetically predicted 1-SD increase of serum IGF-1 levels. RESULTS: For 1-SD increase in IGF-1, the change of eBMD levels was 0.04 g/cm2 (95% CI, 0.01-0.07; P = .011) and the odds ratio of fracture was 0.94 (95% CI, 0.91-0.98; P = .003). The associations persisted with similar magnitude after adjustment for height. The association was consistent for fracture but not for eBMD after excluding genetic instruments that might directly influence these outcomes. The association between IGF-1 and fracture was somewhat attenuated after adjustment for eBMD (odds ratio 0.96; 95% CI, 0.92-0.99; P = .012). CONCLUSION: The present study supports a role for IGF-1 in preventing fracture, possibly and partly mediated by greater bone mineral density.

5.
BMC Med ; 18(1): 370, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33261611

RESUMO

BACKGROUND: Observational studies have shown that milk consumption is inversely associated with colorectal, bladder, and breast cancer risk, but positively associated with prostate cancer. However, whether the associations reflect causality remains debatable. We investigated the potential causal associations of milk consumption with the risk of colorectal, bladder, breast, and prostate cancer using a genetic variant near the LCT gene as proxy for milk consumption. METHODS: We obtained genetic association estimates for cancer from the UK Biobank (n = 367,643 women and men), FinnGen consortium (n = 135,638 women and men), Breast Cancer Association Consortium (n = 228,951 women), and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254 men). Milk consumption was proxied by a genetic variant (rs4988235 or rs182549) upstream of the gene encoding lactase, which catalyzes the breakdown of lactose. RESULTS: Genetically proxied milk consumption was associated with a reduced risk of colorectal cancer. The odds ratio (OR) for each additional milk intake increasing allele was 0.95 (95% confidence interval [CI] 0.91-0.99; P = 0.009). There was no overall association of genetically predicted milk consumption with bladder (OR 0.99; 95% CI 0.94-1.05; P = 0.836), breast (OR 1.01; 95% CI 1.00-1.02; P = 0.113), and prostate cancer (OR 1.01; 95% CI 0.99-1.02; P = 0.389), but a positive association with prostate cancer was observed in the FinnGen consortium (OR 1.07; 95% CI 1.01-1.13; P = 0.026). CONCLUSIONS: Our findings strengthen the evidence for a protective role of milk consumption on colorectal cancer risk. There was no or limited evidence that milk consumption affects the risk of bladder, breast, and prostate cancer.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33303313

RESUMO

OBJECTIVE: Arterial injury in knee trauma is rare but can be devastating if the diagnosis is delayed. The frequency of concomitant arterial injury resulting from knee dislocations remains unclear, and from knee fractures it remains unknown. The primary aim was to investigate the incidence of arterial injury in knee trauma requiring hospitalisation. Secondary aims were to identify risk factors and describe outcome. METHODS: Traumatic popliteal artery injury and knee trauma were identified by International Classification of Diseases (ICD)-10 codes from the Swedish National Inpatient registry (NPR), 1998-2014 and linked with data using the unique personal identification number with the National Registry for vascular surgery (Swedvasc). Risk factors for popliteal artery injury (PAI) such as cause of injury, comorbidities and injury severity were extracted from the NPR. Socio-economic status data and population count came from Statistics Sweden, and cause and date of death from the Swedish Cause of Death Registry. RESULTS: A total of 71 149 admissions due to all knee trauma were identified, and 359 with simultaneous PAIs. Some of those injuries were non-orthopaedic. The proportion of PAI after knee dislocation ranged between 3.4% (46/1370 dislocations or multiligamentous injuries) and 8.2% (46/564 dislocations), and 0.2% after fracture close to the knee (60/36 483). The most common causes of injury with PAI were falls causing knee dislocations and motor vehicle accidents (MVAs) causing fractures. The fact that all 46 injuries occurring after multiligamentous injuries were classified as knee dislocations is probably explained by the fact that the ICD codes are chosen retrospectively when the patient leaves the hospital. CONCLUSION: PAI after knee dislocation is not uncommon, and most frequently caused by a fall. PAI associated with knee fracture is rare and mostly caused by a MVA, while in low energy knee fractures PAI is practically non-existent.

7.
Int J Epidemiol ; 2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33367703

RESUMO

BACKGROUND: We examined whether the inverse association between adherence to a Mediterranean diet and hip fracture risk is mediated by incident type 2 diabetes mellitus (T2DM) and body mass index (BMI). METHODS: We included 50 755 men and women from the Cohort of Swedish Men and the Swedish Mammography Cohort who answered lifestyle and medical questionnaires in 1997 and 2008 (used for calculation of the Mediterranean diet score 9mMED; low, medium, high) and BMI in 1997, and incident T2DM in 1997-2008). The cumulative incidence of hip fracture from the National Patient Register (2009-14) was considered as outcome. RESULTS: We present conditional odds ratios (OR) 9[95% confidence interval, CI) of hip fracture for medium and high adherence to mMED, compared with low adherence. The total effect ORs were 0.82 (0.71, 0.95) and 0.75 (0.62, 0.91), respectively. The controlled direct effect of mMED on hip fracture (not mediated by T2DM, considering BMI as an exposure-induced confounder), calculated using inverse probability weighting of marginal structural models, rendered ORs of 0.82 (0.72, 0.95) and 0.73 (0.60, 0.88), respectively. The natural direct effect ORs (not mediated by BMI or T2DM, calculated using flexible mediation analysis) were 0.82 (0.71, 0.95) and 0.74(0.61, 0.89), respectively. The path-specific indirect and partial indirect natural effects ORs (through BMI or T2DM) were close to 1. CONCLUSIONS: Mediterranean diet has a direct effect on hip fracture risk via pathways other than through T2DM and BMI. We cannot exclude mediating effects of T2DM or BMI, or that their effects cancel each other out.

8.
Clin Nutr ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33199044

RESUMO

BACKGROUND & AIMS: Arachidonic acid (AA) is metabolized by cyclooxygenases and lipoxygenases to pro-inflammatory eicosanoids, which according to experimental research modulate tumor cell proliferation, differentiation, and apoptosis. We employed the Mendelian randomization design to test the hypothesis that higher plasma phospholipid AA concentrations are associated with increased risk of 10 site-specific cancers. METHODS: Two genetic variants associated with plasma phospholipid concentrations of AA (rs174547 in FADS1 [P = 3.0 × 10-971] and rs16966952 in PDXDC1 [P = 2.4 × 10-10]) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium were used as genetic instruments. The associations of those variants with cancer were taken from the UK Biobank (n = 367,643), FinnGen consortium (n = 135,638), International Lung Cancer Consortium (n = 27,209), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254), Breast Cancer Association Consortium (n = 228,951), Ovarian Cancer Association Consortium (n = 66,450), and BioBank Japan (n = 212,453). RESULTS: Higher genetically predicted plasma phospholipid AA concentrations were associated with increased risk of colorectal and lung cancer. Results were consistent across data sources and variants. The combined odds ratios per standard deviation increase of AA concentrations were 1.08 (95% CI 1.05-1.11; P = 6.3 × 10-8) for colorectal cancer and 1.07 (95%CI 1.05-1.10; P = 3.5 × 10-7) for lung cancer. Genetically predicted AA concentrations had a suggestive positive association with esophageal cancer (odds ratio 1.09; 95% CI 1.02-1.17; P = 0.016) but were not associated with cancers of the stomach, pancreas, bladder, prostate, breast, uterus, or ovary. CONCLUSION: These results indicate that AA may be implicated in the development of colorectal and lung cancer and possibly esophageal cancer. Treatments with plasma AA-lowering properties should be evaluated for clinical benefit.

9.
Nat Metab ; 2(10): 1135-1148, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33067605

RESUMO

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.

10.
Clin Nutr ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-33004231

RESUMO

BACKGROUND & AIMS: The impact of dairy consumption on breast cancer development is unclear. We sought to examine associations between long-term consumption of milk and fermented dairy products and risk of breast cancer by estrogen (ER) and progesterone receptor (PR) status and assess whether these associations varied by body weight. METHODS: The population-based Swedish Mammography Cohort included 33,780 women (88.2% postmenopausal), with no history of cancer or diabetes at baseline (1997). Long-term consumption of dairy products was assessed using a self-administered food-frequency questionnaire in 1987 and 1997. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 16.6 years of follow-up (559,286 person-years), 1870 total breast cancer cases were diagnosed (1162 ER+/PR+; 195 ER-/PR-). High long-term non-fermented milk consumption was associated with increased ER+/PR+ breast cancer incidence, HR = 1.30, 95%CI:1.02-1.65 for the average of 1987 and 1997 intake ≥2 vs. 0 servings/day and this increased risk was limited to women with BMI<25 kg/m2 HR = 1.55, 95%CI:1.08-2.21, while no significant associations with milk consumption were observed with ER-/PR- breast cancer. In contrast, consumption of fermented dairy products was inversely associated with ER-/PR- breast cancer (for consistently high intake ≥3 vs. <1 servings/day HR = 0.28, 95%CI:0.10-0.78), but not clear association was observed for ER+/PR+ (HR = 0.89, 95%CI:0.69-1.14). CONCLUSIONS: In this cohort of mainly postmenopausal women, high long-term consumption of milk was associated with increased risk of ER+/PR+ breast cancer. In contrast, high long-term consumption of fermented dairy products was associated with decreased risk of ER-/PR- breast cancer.

11.
Stroke ; 51(11): 3279-3285, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32895015

RESUMO

BACKGROUND AND PURPOSE: Studies of sleep duration in relation to specific types of stroke are scarce. Moreover, the results are inconclusive and causality remains unclear. Our objective was to investigate whether sleep duration is associated with risk of stroke and its types using observational and Mendelian randomization designs. METHODS: The prospective study included 79 881 women and men (45-79 years of age) who were followed up for incident stroke or death over a mean follow-up of 14.6 years (1 164 646 person-years) through linkage to Swedish Registers. For the Mendelian randomization study, single-nucleotide polymorphisms associated with sleep duration were identified from a genome-wide association study. Summarized data for genetic associations with stroke were obtained from publicly available data of the MEGASTROKE and the International Stroke Genetics Consortia. RESULTS: Compared with normal sleep duration, long sleep (≥9 hours per day) was associated with increased risk of total and ischemic stroke (hazard ratios [95% CI], 1.12 [1.03-1.22] and 1.14 [1.03-1.24], respectively), whereas short sleep (<7 h/d) was linked to higher risk of intracerebral hemorrhage (hazard ratio [95% CI], 1.21 [1.03-1.41]). The 2-sample Mendelian randomization analysis supported no causal association of short or long sleep duration with ischemic stroke as a whole. CONCLUSIONS: In a prospective study, long sleep duration was associated with increased risk of total and ischemic stroke, whereas short sleep was linked to increased risk of intracerebral hemorrhage. However, the Mendelian randomization analysis did not show a significant detrimental effect of short or long sleep duration on the risk of total stroke or stroke types.

12.
Int J Cancer ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895918

RESUMO

Studies of sleep duration in relation to the risk of site-specific cancers other than breast cancer are scarce. Furthermore, the available results are inconclusive and the causality remains unclear. We aimed to investigate the potential causal associations of sleep duration with overall and site-specific cancers using the Mendelian randomization (MR) design. Single-nucleotide polymorphisms associated with the sleep traits identified from a genome-wide association study were used as instrumental variables to estimate the association with overall cancer and 22 site-specific cancers among 367 586 UK Biobank participants. A replication analysis was performed using data from the FinnGen consortium (up to 121 579 individuals). There was suggestive evidence that genetic liability to short-sleep duration was associated with higher odds of cancers of the stomach (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.15-4.30; P = .018), pancreas (OR, 2.18; 95% CI, 1.32-3.62; P = .002) and colorectum (OR, 1.48; 95% CI, 1.12-1.95; P = .006), but with lower odds of multiple myeloma (OR, 0.47; 95% CI, 0.22-0.99; P = .047). Suggestive evidence of association of genetic liability to long-sleep duration with lower odds of pancreatic cancer (OR, 0.44; 95% CI, 0.25-0.79; P = .005) and kidney cancer (OR, 0.44; 95% CI, 0.21-0.90; P = .025) was observed. However, none of these associations passed the multiple comparison threshold and two-sample MR analysis using FinnGen data did not confirm these findings. In conclusion, this MR study does not provide strong evidence to support causal associations of sleep duration with risk of overall and site-specific cancers. Further MR studies are required.

13.
PLoS Med ; 17(9): e1003331, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941436

RESUMO

BACKGROUND: It is unclear whether the effect on mortality of a higher body mass index (BMI) can be compensated for by adherence to a healthy diet and whether the effect on mortality by a low adherence to a healthy diet can be compensated for by a normal weight. We aimed to evaluate the associations of BMI combined with adherence to a Mediterranean-like diet on all-cause and cardiovascular disease (CVD) mortality. METHODS AND FINDINGS: Our longitudinal cohort design included the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM) (1997-2017), with a total of 79,003 women (44%) and men (56%) and a mean baseline age of 61 years. BMI was categorized into normal weight (20-24.9 kg/m2), overweight (25-29.9 kg/m2), and obesity (30+ kg/m2). Adherence to a Mediterranean-like diet was assessed by means of the modified Mediterranean-like diet (mMED) score, ranging from 0 to 8; mMED was classified into 3 categories (0 to <4, 4 to <6, and 6-8 score points), forming a total of 9 BMI × mMED combinations. We identified mortality by use of national Swedish registers. Cox proportional hazard models with time-updated information on exposure and covariates were used to calculate the adjusted hazard ratios (HRs) of mortality with their 95% confidence intervals (CIs). Our HRs were adjusted for age, baseline educational level, marital status, leisure time physical exercise, walking/cycling, height, energy intake, smoking habits, baseline Charlson's weighted comorbidity index, and baseline diabetes mellitus. During up to 21 years of follow-up, 30,389 (38%) participants died, corresponding to 22 deaths per 1,000 person-years. We found the lowest HR of all-cause mortality among overweight individuals with high mMED (HR 0.94; 95% CI 0.90, 0.98) compared with those with normal weight and high mMED. Using the same reference, obese individuals with high mMED did not experience significantly higher all-cause mortality (HR 1.03; 95% CI 0.96-1.11). In contrast, compared with those with normal weight and high mMED, individuals with a low mMED had a high mortality despite a normal BMI (HR 1.60; 95% CI 1.48-1.74). We found similar estimates among women and men. For CVD mortality (12,064 deaths) the findings were broadly similar, though obese individuals with high mMED retained a modestly increased risk of CVD death (HR 1.29; 95% CI 1.16-1.44) compared with those with normal weight and high mMED. A main limitation of the present study is the observational design with self-reported lifestyle information with risk of residual or unmeasured confounding (e.g., genetic liability), and no causal inferences can be made based on this study alone. CONCLUSIONS: These findings suggest that diet quality modifies the association between BMI and all-cause mortality in women and men. A healthy diet may, however, not completely counter higher CVD mortality related to obesity.


Assuntos
Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/mortalidade , Dieta Mediterrânea/psicologia , Idoso , Índice de Massa Corporal , Causas de Morte , Estudos de Coortes , Dieta Saudável , Feminino , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/dietoterapia , Sobrepeso , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar , Suécia
14.
J Bone Joint Surg Am ; 102(17): 1486-1494, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32701713

RESUMO

BACKGROUND: In Sweden, approximately 1 in 4 women who are ≥50 years of age will sustain a hip fracture. Patients treated for a femoral shaft fracture are likely to have an even higher risk. We hypothesized that intramedullary nails protecting the femoral neck reduce the risk of subsequent hip fracture and allow the patient to avoid a challenging reoperation. METHODS: Between 2008 and 2010, 5,475 fractures of the femoral shaft, in patients who were ≥55 years of age, were registered in a national registry in Sweden. Of these patients, 897 fulfilled the inclusion criteria. We used radiographs and register data to identify the reasons for and the types of reoperation that occurred between the index surgical procedure and December 31, 2014. The categories of implants were determined through a review of radiographs as intramedullary nails with and without femoral neck protection. Reoperations related to peri-implant fractures (including hip fractures) were analyzed as a subgroup of all major reoperations. Multivariable-adjusted, cause-specific hazard ratios (HRs) were calculated to compare the risk of reoperation between cases with nails with and without femoral neck protection. RESULTS: Among the 897 patients, a total of 82 reoperations were performed. In 640 patients who were treated with intramedullary nails with femoral neck protection, there were 7 peri-implant fractures (no hip fractures) and 27 major reoperations. Among the 257 patients who were treated with intramedullary nails without femoral neck protection, 14 peri-implant hip fractures and 24 major reoperations were identified. Patients who received nails with femoral neck protection had a lower hazard for any peri-implant fracture (multivariable-adjusted cause-specific HR, 0.19 [95% confidence interval (CI), 0.07 to 0.5]) and major reoperation (multivariable-adjusted cause-specific HR, 0.51 [95% CI, 0.28 to 0.92]). CONCLUSIONS: Intramedullary nails with femoral neck protection in the treatment of low-energy femoral shaft fractures prevent secondary hip fractures and decrease the overall risk of reoperation for 4 to 6 years postoperatively. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

15.
PLoS Med ; 17(7): e1003178, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32701947

RESUMO

BACKGROUND: Smoking is a well-established cause of lung cancer and there is strong evidence that smoking also increases the risk of several other cancers. Alcohol consumption has been inconsistently associated with cancer risk in observational studies. This mendelian randomisation (MR) study sought to investigate associations in support of a causal relationship between smoking and alcohol consumption and 19 site-specific cancers. METHODS AND FINDINGS: We used summary-level data for genetic variants associated with smoking initiation (ever smoked regularly) and alcohol consumption, and the corresponding associations with lung, breast, ovarian, and prostate cancer from genome-wide association studies consortia, including participants of European ancestry. We additionally estimated genetic associations with 19 site-specific cancers among 367,643 individuals of European descent in UK Biobank who were 37 to 73 years of age when recruited from 2006 to 2010. Associations were considered statistically significant at a Bonferroni corrected p-value below 0.0013. Genetic predisposition to smoking initiation was associated with statistically significant higher odds of lung cancer in the International Lung Cancer Consortium (odds ratio [OR] 1.80; 95% confidence interval [CI] 1.59-2.03; p = 2.26 × 10-21) and UK Biobank (OR 2.26; 95% CI 1.92-2.65; p = 1.17 × 10-22). Additionally, genetic predisposition to smoking was associated with statistically significant higher odds of cancer of the oesophagus (OR 1.83; 95% CI 1.34-2.49; p = 1.31 × 10-4), cervix (OR 1.55; 95% CI 1.27-1.88; p = 1.24 × 10-5), and bladder (OR 1.40; 95% CI 1.92-2.65; p = 9.40 × 10-5) and with statistically nonsignificant higher odds of head and neck (OR 1.40; 95% CI 1.13-1.74; p = 0.002) and stomach cancer (OR 1.46; 95% CI 1.05-2.03; p = 0.024). In contrast, there was an inverse association between genetic predisposition to smoking and prostate cancer in the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (OR 0.90; 95% CI 0.83-0.98; p = 0.011) and in UK Biobank (OR 0.90; 95% CI 0.80-1.02; p = 0.104), but the associations did not reach statistical significance. We found no statistically significant association between genetically predicted alcohol consumption and overall cancer (n = 75,037 cases; OR 0.95; 95% CI 0.84-1.07; p = 0.376). Genetically predicted alcohol consumption was statistically significantly associated with lung cancer in the International Lung Cancer Consortium (OR 1.94; 95% CI 1.41-2.68; p = 4.68 × 10-5) but not in UK Biobank (OR 1.12; 95% CI 0.65-1.93; p = 0.686). There was no statistically significant association between alcohol consumption and any other site-specific cancer. The main limitation of this study is that precision was low in some analyses, particularly for analyses of alcohol consumption and site-specific cancers. CONCLUSIONS: Our findings support the well-established relationship between smoking and lung cancer and suggest that smoking may also be a risk factor for cancer of the head and neck, oesophagus, stomach, cervix, and bladder. We found no evidence supporting a relationship between alcohol consumption and overall or site-specific cancer risk.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Análise da Randomização Mendeliana/métodos , Neoplasias/etiologia , Fumar/genética , Bancos de Espécimes Biológicos , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Reino Unido
16.
Diabetologia ; 63(9): 1775-1782, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32548700

RESUMO

AIMS/HYPOTHESIS: Abnormal serum IGF-1 levels are associated with an increased risk of type 2 diabetes and cardiovascular disease. However, the causal role of IGF-1 levels within the normal range in cardiometabolic disease remains unclear. We employed Mendelian randomisation to explore the associations between genetically predicted serum IGF-1 levels and cardiometabolic diseases. METHODS: Serum IGF-1 levels were predicted using 416 SNPs associated with IGF-1 levels among 358,072 individuals in UK Biobank. Genetic association estimates for the outcomes were obtained from consortia of type 2 diabetes (74,124 cases, 824,006 controls), coronary artery disease (60,801 cases, 123,504 controls), heart failure (47,309 cases, 930,014 controls), atrial fibrillation (65,446 cases, 522,744 controls), and ischaemic stroke (60,341 cases, 454,450 controls). RESULTS: Genetic predisposition to elevated serum IGF-1 levels was associated with higher risk of type 2 diabetes and coronary artery disease. The OR (95% CI) per SD increment in IGF-1 level was 1.14 (1.05, 1.24) for type 2 diabetes and 1.09 (1.02, 1.16) for coronary artery disease. The association between IGF-1 and coronary artery disease was attenuated after adjustment for type 2 diabetes (OR 1.06 [95% CI 1.00, 1.13]), suggesting that the association may be partly mediated via type 2 diabetes. There was limited evidence of associations between IGF-1 levels and heart failure, atrial fibrillation and ischaemic stroke. CONCLUSIONS/INTERPRETATION: This study found evidence that increased IGF-1 levels may be causally associated with higher risk of type 2 diabetes. Graphical abstract.

17.
Nutrients ; 12(5)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32413977

RESUMO

Mortality in relation to type of milk intake is unclear. We present mortality rates by intake of non-fermented milk fat content type and examine the degree of bias when other fat content types of non-fermented milk are kept in the reference category. For this purpose, we used a longitudinal cohort consisting of 61,433 women who had been administered food frequency questionnaires in 1987-1990 and in 1997, and analyzed time to death. Non-fermented milk consumption was divided into low ≤0.5%, medium 1.5%, or high fat 3%. For each specific type of milk, the first analysis (A) is restricted to those who consumed less than one serving per day of the other milk subtypes. In the second analysis (B), everyone is retained, i.e., leading to a reference category "contaminated" with other milk consumers. During follow-up, 22,391 women died. Highest (≥3 glasses/day) vs. lowest consumption category of milk (<1 glass/day) with 0.5% fat content was associated with a multivariable hazard ratio (HR) of 1.71 (95%CI 1.57-1.86) in analysis A, whereas the same comparison with a "contaminated" reference category in analysis B provided a HR of 1.34 (95%CI 1.24-1.45), p-value for homogeneity <0.0001. The corresponding HRs for 1.5% fat milk were: 1.82 (95%CI 1.63-2.04) and 1.38 (95%CI 1.25-1.51), and for 3% fat milk 1.95 (95%CI 1.77-2.15) and 1.40 (95%CI 1.29-1.52). HR for ≥3 glasses/day of total milk was 1.95 (95%CI 1.84-2.06). We observe a higher mortality in women with high milk consumption, irrespective of milk fat content. A "contaminated" reference group substantially attenuates the actual estimates.

18.
Circ Genom Precis Med ; 13(3): e002814, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32367730

RESUMO

BACKGROUND: The causal role of alcohol consumption for cardiovascular disease remains unclear. We used Mendelian randomization (MR) to predict the effect of alcohol consumption on 8 cardiovascular diseases. METHODS: Up to 94 single-nucleotide polymorphisms were used as instrumental variables for alcohol consumption. Genetic association estimates for cardiovascular diseases were obtained from large-scale consortia and UK Biobank. Analyses were conducted using the inverse variance-weighted, weighted median, MR-PRESSO, MR-Egger, and multivariable MR methods. RESULTS: Genetically predicted alcohol consumption was consistently associated with stroke and peripheral artery disease across the different analyses. The odds ratios (ORs) per 1-SD increase of log-transformed alcoholic drinks per week were 1.27 ([95% CI, 1.12-1.45] P=2.87×10-4) for stroke and 3.05 ([95% CI, 1.92-4.85] P=2.30×10-6) for peripheral artery disease in the inverse variance-weighted analysis. There was some evidence for positive associations of genetically predicted alcohol consumption with coronary artery disease (OR, 1.16 [95% CI, 1.00-1.36]; P=0.052), atrial fibrillation (OR, 1.17 [95% CI, 1.00-1.37]; P=0.050), and abdominal aortic aneurysm (OR, 2.60 [95% CI, 1.15-5.89]; P=0.022) in the inverse variance-weighted analysis. These associations were somewhat attenuated in multivariable MR analysis adjusted for smoking initiation. There was no evidence of associations of genetically predicted alcohol consumption with heart failure (OR, 1.00 [95% CI, 0.68-1.47]; P=0.996), venous thromboembolism (OR, 1.04 [95% CI, 0.77-1.39]; P=0.810), and aortic valve stenosis (OR, 1.03 [95% CI, 0.56-1.90]; P=0.926). CONCLUSIONS: This study provides evidence of a causal relationship between higher alcohol consumption and increased risk of stroke and peripheral artery disease. The causal role of alcohol consumption for other cardiovascular diseases requires further research.

19.
Eur Heart J ; 41(35): 3304-3310, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32300774

RESUMO

AIMS: The aim of this study was to use Mendelian randomization (MR) to determine the causality of the association between smoking and 14 different cardiovascular diseases (CVDs). METHODS AND RESULTS: Our primary genetic instrument comprised 361 single-nucleotide polymorphisms (SNPs) associated with smoking initiation (ever smoked regularly) at genome-wide significance. Data on the associations between the SNPs and 14 CVDs were obtained from the UK Biobank study (N = 367 643 individuals), CARDIoGRAMplusC4D consortium (N = 184 305 individuals), Atrial Fibrillation Consortium (2017 dataset; N = 154 432 individuals), and Million Veteran Program (MVP; N = 190 266 individuals). The main analyses were conducted using the random-effects inverse-variance weighted method and complemented with multivariable MR analyses and the weighted median and MR-Egger approaches. Genetic predisposition to smoking initiation was most strongly and consistently associated with higher odds of coronary artery disease, heart failure, abdominal aortic aneurysm, ischaemic stroke, transient ischaemic attack, peripheral arterial disease, and arterial hypertension. Genetic predisposition to smoking initiation was additionally associated with higher odds of deep vein thrombosis and pulmonary embolism in the UK Biobank but not with venous thromboembolism in the MVP. There was limited evidence of causal associations of smoking initiation with atrial fibrillation, aortic valve stenosis, thoracic aortic aneurysm, and intracerebral and subarachnoid haemorrhage. CONCLUSION: This MR study supports a causal association between smoking and a broad range of CVDs, in particular, coronary artery disease, heart failure, abdominal aortic aneurysm, ischaemic stroke, transient ischaemic attack, peripheral arterial disease, and arterial hypertension.

20.
J Clin Sleep Med ; 16(1): 9-18, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31957658

RESUMO

STUDY OBJECTIVES: To investigate relationships between sleep duration and adherence to healthy diets, but also associations with meal patterns, in a large population-based cohort. METHODS: Participants (n = 23,829, males and females, aged 45 to 75 years) from the Swedish EpiHealth cohort study were included in a cross-sectional analysis. The participants filled out an extensive Internet-based questionnaire, and also visited a test center for anthropometric measurements and blood sampling. Sleep duration was classified as short (< 6 h/night; n = 1,862), normal (6 to less fewer than 9 h/night; n = 19,907) and long sleep (≥ 9 h/night; n = 858). In addition, a combination variable of sleep duration (short/normal/long) and sleep quality (good/poor) was constructed, giving six categories. Adherence to a healthy diet was assessed using the modified Mediterranean diet (mMED) score and the Healthy Nordic Food Index (HNFI) score based on food groups from a food frequency questionnaire. A regular meal pattern was considered if the participant had breakfast, lunch and dinner on a daily basis. RESULTS: Compared with normal sleepers, short sleepers displayed lower adherence to a healthy diet when using both the mMED score (adjusted odds ratio = 0.70; 95% confidence interval 0.56-0.88) and the HNFI score (0.70; 0.56-0.88). When combining sleep duration and sleep quality, short sleepers with poor sleep quality showed an independent relationship with low adherence to a healthy diet (0.67; 0.52-0.86) compared with normal sleepers with good sleep quality. In addition, both short sleepers (0.71; 0.62-0.82) and long sleepers (0.75; 0.62-0.91) showed low adherence to regular meal patterns, compared with normal sleepers. Furthermore, short sleepers with poor sleep quality had reduced odds of having a regular meal pattern (0.67; 0.57-0.79) as compared with normal sleepers with good sleep quality. CONCLUSIONS: Short sleep duration combined with poor sleep quality is associated with low adherence to a healthy diet and regular meal patterns.

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