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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 show adverse metabolic effects in animal models and in humans, but it is yet unknown if addition of fermentable dietary fiber can mitigate such effects. This study investigate 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) receive different carbohydrates at isocaloric conditions for 12 weeks 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 n-6 polyunsaturated fatty acids (n-6 PUFA) in all diets except for in 7) starch + olive oil (negative control). The rats fed the galactose and galactose + FOS diets exhibit lower body weight than other groups. High-galactose diets has more pronounced effects on metabolic factors and gut permeability than high-fructose diets. High-fructose diets show less pronounced effect on these selected markers. No differences in inflammatory markers are detected for any of the diets. CONCLUSIONS: The 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 are difficult to determine conclusively for the conditions tested.

2.
Nat Commun ; 12(1): 1236, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33623038

RESUMO

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10-180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

3.
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.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33420416

RESUMO

BACKGROUND: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). MATERIALS AND METHOD: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy. RESULTS: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer. CONCLUSIONS: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

5.
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.

6.
Cancers (Basel) ; 12(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158149

RESUMO

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

7.
Eur J Epidemiol ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33128203

RESUMO

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose-response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6-7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively-and nonlinearly-associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18-20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m2, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18-20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC.

8.
Int J Cancer ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038280

RESUMO

Obesity is considered a chronic inflammatory state characterized by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potential causal associations of specific adipokines (adiponectin, leptin, soluble leptin receptor [sOB-R] and plasminogen activator inhibitor-1 [PAI-1]) with five obesity-related cancers (colorectal, pancreatic, renal cell carcinoma [RCC], ovarian and endometrial) using Mendelian randomization (MR) methods. We used summary-level data from large genetic consortia for 114 530 cancer cases and 245 284 controls. We constructed genetic instruments using 18 genetic variants for adiponectin, 2 for leptin and 4 for both sOB-R and PAI-1 (P value for inclusion<5 × 10-8 ). Causal estimates were obtained using two-sample MR methods. In the inverse-variance weighted models, we found an inverse association between adiponectin and risk of colorectal cancer (odds ratio per 1 µg/mL increment in adiponectin concentration: 0.90 [95% confidence interval = 0.84-0.97]; P = .01); but, evidence of horizontal pleiotropy was detected and the association was not present when this was taken into consideration. No association was found for adiponectin and risks of pancreatic cancer, RCC, ovarian cancer and endometrial cancer. Leptin, sOB-R and PAI-1 were also similarly unrelated to risk of obesity-related cancers. Despite the large sample size, our MR analyses do not support causal effects of circulating adiponectin, leptin, sOB-R and PAI-1 concentrations on the development of five obesity-related cancers.

9.
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.

10.
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
11.
Cancer Epidemiol Biomarkers Prev ; 29(10): 2010-2018, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32732252

RESUMO

BACKGROUND: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. METHODS: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. RESULTS: Most associations did not vary by tumor site (P het ≥ 0.05). Associations between first pregnancy (P het = 0.04), tubal ligation (P het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. CONCLUSIONS: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. IMPACT: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

12.
Eur J Clin Nutr ; 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782386

RESUMO

BACKGROUND/OBJECTIVES: Whole-grain (WG) intake has been associated with a lowered risk of developing type 2 diabetes, cardiovascular disease, and some cancers in epidemiological studies. Reduced subclinical inflammation could be one important mechanism behind such associations. This study investigated whether high long-term WG rye and wheat intakes were associated with lower concentrations of biomarkers of inflammation, endothelial function, and protein biomarkers associated with cardiovascular disease. SUBJECTS/METHODS: We assessed WG intake by food frequency questionnaire (FFQ) and by measuring alkylresorcinols (ARs) in plasma and adipose tissue, respectively. Selected biomarkers in free-living 109 women and 149 men were analyzed from two clinical subcohort studies (Swedish Mammography Cohort-Clinical (SMC-C) and Cohort of Swedish Men-Clinical (COSM-C), respectively. Total WG rye and wheat (WGRnW) and the ratio of WG rye to WG rye and wheat (WGR/WGRnW) were estimated from FFQs. ARs were measured in plasma and adipose tissue by gas chromatography-mass spectrometry (GC-MS) and the biomarkers by ELISA. RESULTS: We found no consistent associations between WG intake assessed by different methods and the selected biomarkers. However, WGRnW intake was inversely associated with cathepsin S (P-trend < 0.05) and total AR and C17:0/C21:0 in plasma were inversely associated with the endostatin concentration (P-trend < 0.05) adjusted for BMI, age, and sex. CONCLUSION: The results give limited support to the hypothesis that a high WG wheat and rye intake is associated with lower concentrations of common biomarkers of inflammation and CVD that have previously been reported inversely associated with WG intake or an overall healthy lifestyle.

13.
Am J Hum Genet ; 107(3): 432-444, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32758450

RESUMO

Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.


Assuntos
Neoplasias Colorretais/epidemiologia , Predisposição Genética para Doença , Genoma Humano/genética , Medição de Risco , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Teorema de Bayes , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
14.
Int J Cancer ; 147(11): 3090-3101, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32525569

RESUMO

A low intake of fruits and vegetables is a risk factor for gastric cancer, although there is uncertainty regarding the magnitude of the associations. In our study, the relationship between fruits and vegetables intake and gastric cancer was assessed, complementing a previous work on the association betweenconsumption of citrus fruits and gastric cancer. Data from 25 studies (8456 cases and 21 133 controls) with information on fruits and/or vegetables intake were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age and the main known risk factors for gastric cancer) odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Exposure-response relations, including linear and nonlinear associations, were modeled using one- and two-order fractional polynomials. Gastric cancer risk was lower for a higher intake of fruits (OR: 0.76, 95% CI: 0.64-0.90), noncitrus fruits (OR: 0.86, 95% CI: 0.73-1.02), vegetables (OR: 0.68, 95% CI: 0.56-0.84), and fruits and vegetables (OR: 0.61, 95% CI: 0.49-0.75); results were consistent across sociodemographic and lifestyles categories, as well as study characteristics. Exposure-response analyses showed an increasingly protective effect of portions/day of fruits (OR: 0.64, 95% CI: 0.57-0.73 for six portions), noncitrus fruits (OR: 0.71, 95% CI: 0.61-0.83 for six portions) and vegetables (OR: 0.51, 95% CI: 0.43-0.60 for 10 portions). A protective effect of all fruits, noncitrus fruits and vegetables was confirmed, supporting further dietary recommendations to decrease the burden of gastric cancer.

15.
Acta Cardiol ; : 1-6, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32479142

RESUMO

Aims: Previous studies have found that excessive sport activities are associated with an increased risk of atrial fibrillation (AF). Whether occupational physical activity (OPA) increases the risk for AF is not well studied. We aimed to examine whether OPA influences the risk of AF.Methods: 80,922 men and women, free from AF, completed in 1997 a questionnaire about their OPA at that time (baseline), and also retrospectively in 1997 their OPA at the age of 30 and 50 years. Participants were categorised into three groups (low, medium and high) based on OPA load. Participants were followed-up in the Swedish National Patient Register for ascertainment of AF. Cox proportional hazards regression models were used to estimate relative risks (RR) with 95% confidence intervals (CI), adjusted for potential confounders.Results: 11,614 cases of AF were diagnosed during follow-up time of up to 17 years. We observed an increased risk of AF in relation to increased load of OPA regardless of age. Compared with men who reported a low load of OPA, the multivariable RR (95% CI) for men with a high load was 1.10 (1.03-1.17) at 30 years, 1.11 (1.04-1.17) at 50 years and 1.19 (1.10-1.29) at baseline. The results for women were similar with multivariable RR of 1.16 (1.06-1.27) at 30 years, 1.14 (1.05-1.24) at 50 years and 1.11 (0.99-1.24) at baseline.Conclusion: These findings suggest that high load of OPA previous in life may play a role in increasing the risk for AF in both men and women.

16.
J Hepatol ; 73(4): 863-872, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32437829

RESUMO

BACKGROUND & AIMS: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. METHODS: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. RESULTS: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. CONCLUSION: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. LAY SUMMARY: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.

17.
Eur J Nutr ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444887

RESUMO

PURPOSE: Red meat consumption is positively associated with type 1 (T1D) and type 2 (T2D) diabetes. We investigated if red meat consumption increases the risk of latent autoimmune diabetes in adults (LADA) and T2D, and potential interaction with family history of diabetes (FHD), HLA and TCF7L2 genotypes. METHODS: Analyses were based on Swedish case-control data comprising incident cases of LADA (n = 465) and T2D (n = 1528) with matched, population-based controls (n = 1789; n = 1553 in genetic analyses). Multivariable-adjusted ORs in relation to self-reported processed and unprocessed red meat intake were estimated by conditional logistic regression models. Attributable proportion (AP) due to interaction was used to assess departure from additivity of effects. RESULTS: Consumption of processed red meat was associated with increased risk of LADA (per one servings/day OR 1.27, 95% CI 1.07-1.52), whereas no association was observed for unprocessed red meat. For T2D, there was no association with red meat intake once BMI was taken into account. The combination of high (> 0.3 servings/day vs. less) processed red meat intake and high-risk HLA-DQB1 and -DRB1 genotypes yielded OR 8.05 (95% CI 4.86-13.34) for LADA, with indications of significant interaction (AP 0.53, 95% CI 0.32-0.73). Results were similar for the combination of FHD-T1D and processed red meat. No interaction between processed red meat intake and FHD-T2D or risk variants of TCF7L2 was seen in relation to LADA or T2D. CONCLUSION: Consumption of processed but not unprocessed red meat may increase the risk of LADA, especially in individuals with FHD-T1D or high-risk HLA genotypes.

18.
Br J Nutr ; 124(6): 611-619, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32321598

RESUMO

At present, analysis of diet and bladder cancer (BC) is mostly based on the intake of individual foods. The examination of food combinations provides a scope to deal with the complexity and unpredictability of the diet and aims to overcome the limitations of the study of nutrients and foods in isolation. This article aims to demonstrate the usability of supervised data mining methods to extract the food groups related to BC. In order to derive key food groups associated with BC risk, we applied the data mining technique C5.0 with 10-fold cross-validation in the BLadder cancer Epidemiology and Nutritional Determinants study, including data from eighteen case-control and one nested case-cohort study, compromising 8320 BC cases out of 31 551 participants. Dietary data, on the eleven main food groups of the Eurocode 2 Core classification codebook, and relevant non-diet data (i.e. sex, age and smoking status) were available. Primarily, five key food groups were extracted; in order of importance, beverages (non-milk); grains and grain products; vegetables and vegetable products; fats, oils and their products; meats and meat products were associated with BC risk. Since these food groups are corresponded with previously proposed BC-related dietary factors, data mining seems to be a promising technique in the field of nutritional epidemiology and deserves further examination.


Assuntos
Mineração de Dados , Alimentos , Neoplasias da Bexiga Urinária/epidemiologia , Algoritmos , Estudos de Casos e Controles , Dieta , Feminino , Humanos , Incidência , Internacionalidade , Masculino , Fatores de Risco
19.
Cancer Med ; 9(10): 3563-3573, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32207560

RESUMO

BACKGROUND: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology. METHODS: To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2. RESULTS: Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ). CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.

20.
Br J Cancer ; 122(10): 1562-1570, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32210367

RESUMO

BACKGROUND: In 2018, the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) issued revised recommendations for cancer prevention. We examined the relation between adherence to these recommendations and risk of total cancer in two population-based Swedish prospective cohorts (29,451 men and 25,349 women). METHODS: Standardized-WCRF/AICR 2018 and simplified-WCRF/AICR 2018 adherence scores were constructed based on the WCRF/AICR recommendations for body weight, physical activity, diet, alcohol consumption and dietary supplement use. Data were collected using a self-administered questionnaire. RESULTS: During the 15.4 years of follow-up, 12,693 incident cancers were ascertained. The multivariable HR between extreme categories of the Standardized-WCRF/AICR 2018 score (4.1-7 vs. 0-2) was 0.88 (95% CI = 0.82-0.95) and for the Simplified score (5-8 vs. 0-2) was 0.85 (95% CI = 0.80-0.90); each 1-score increment in recommendation adherence was associated with 3% (95% CI = 1-5%) and 4% (95% CI = 2-5%) decreased risk, respectively. Based on the Simplified scoring, most participants (>90%) did not meet WCRF/AICR 2018 recommendations regarding consumption of plant foods, limited consumption of red/processed meat and 'fast food'/processed food, and <50% of participants met the weight and physical activity recommendations. CONCLUSIONS: Adherence to the 2018WCRF/AICR recommendations substantially reduced the risk of total cancer. Given that many people do not meet the recommendations, there is a great potential for cancer prevention.

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