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1.
J Natl Cancer Inst ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688720

RESUMO

BACKGROUND: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive (OC) use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. METHODS: LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26,204 controls and 21,267 cases from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models to expected estimates assuming one year of ovulation suppression has the same effect regardless of source. RESULTS: LOY was associated with increased EOC risk (ORs per year increase: 1.014 (95%CI 1.009-1.020) to 1.044 (95%CI 1.041-1.048)). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for OC use and pregnancies were 4.45 times and 12-15 fold greater than expected, respectively. LOY was associated with high-grade serous (HGSOC), low-grade serous (LGSOC), endometrioid, and clear cell histotypes (ORs per year increase: 1.054, 1.040, 1.065, and 1.098, respectively), but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for HGSOC but larger than expected for LGSOC, endometrioid, and clear cell histotypes. CONCLUSIONS: LOY is positively associated with non-mucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.

2.
Eur J Epidemiol ; 38(1): 11-29, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36593337

RESUMO

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50- < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100- < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95-1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.


Assuntos
Neoplasias da Mama , Deficiência de Vitamina D , Humanos , Feminino , Estudos Prospectivos , Fatores de Risco , Vitamina D , Calcifediol , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia
3.
Int J Cancer ; 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36715363

RESUMO

Glyceraldehyde-derived advanced glycation end products (glycer-AGEs) could contribute to colorectal cancer development and progression due to their pro-oxidative and pro-inflammatory properties. However, the association of glycer-AGEs with mortality after colorectal cancer diagnosis has not been previously investigated. Circulating glycer-AGEs were measured by competitive ELISA. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for associations of circulating glycer-AGEs concentrations with CRC-specific and all-cause mortality among 1,034 colorectal cancer (CRC) cases identified within the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1993 and 2013. During a mean of 48 months of follow-up, 529 participants died (409 from CRC). Glycer-AGEs were statistically significantly positively associated with CRC-specific (HRQ5 vs Q1 =1.53, 95%CI: 1.04-2.25, Ptrend =0.002) and all-cause (HRQ5 vs Q1 =1.62, 95%CI: 1.16-2.26, Ptrend <0.001) mortality among individuals with CRC. There was suggestion of a stronger association between glycer-AGEs and CRC-specific mortality among patients with distal colon cancer (per SD increment: HRproximal colon =1.02, 95%CI: 0.74-1.42; HRdistal colon =1.51, 95%CI: 1.20-1.91; Peffect modification =0.02). The highest HR was observed among CRC cases in the highest body mass index (BMI) and glycer-AGEs category relative to lowest BMI and glycer-AGEs category for both CRC-specific (HR=1.78, 95%CI: 1.02-3.01) and all-cause mortality (HR=2.15, 95%CI: 1.33-3.47), although no statistically significant effect modification was observed. Our study found that pre-diagnostic circulating glycer-AGEs are positively associated with CRC-specific and all-cause mortality among individuals with CRC. Further investigations in other populations and stratifying by tumor location and BMI are warranted. This article is protected by copyright. All rights reserved.

4.
Age Ageing ; 52(1)2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36702514

RESUMO

BACKGROUND: The European Working Group on Sarcopenia in Older People (EWGSOP) updated in 2018 the cut-off points for low grip strength to assess sarcopenia based on pooled data from 12 British studies. OBJECTIVE: Comparison of the EWGSOP2 cut-off points for low grip strength to those derived from a large German sample. METHODS: We assessed the grip strength distribution across age and derived low grip strength cut-off points for men and women (peak mean -2.5 × SD) based on 200,389 German National Cohort (NAKO) participants aged 19-75 years. In 1,012 Cooperative Health Research in the Region of Augsburg (KORA)-Age participants aged 65-93 years, we calculated the age-standardised prevalence of low grip strength and time-dependent sensitivity and specificity for all-cause mortality. RESULTS: Grip strength increased in the third and fourth decade of life and declined afterwards. Calculated cut-off points for low grip strength were 29 kg for men and 18 kg for women. In KORA-Age, the age-standardised prevalence of low grip strength was 1.5× higher for NAKO-derived (17.7%) compared to EWGSOP2 (11.7%) cut-off points. NAKO-derived cut-off points yielded a higher sensitivity and lower specificity for all-cause mortality. CONCLUSIONS: Cut-off points for low grip strength from German population-based data were 2 kg higher than the EWGSOP2 cut-off points. Higher cut-off points increase the sensitivity, thereby suggesting an intervention for more patients at risk, while other individuals might receive additional diagnostics/treatment without the urgent need. Research on the effectiveness of intervention in patients with low grip strength defined by different cut-off points is needed.


Assuntos
Sarcopenia , Idoso , Masculino , Humanos , Feminino , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Avaliação Geriátrica , Força da Mão , Prevalência
5.
Br J Cancer ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460776

RESUMO

BACKGROUND: Classical anthropometric traits may fail to fully represent the relationship of weight, adiposity, and height with cancer risk. We investigated the associations of body shape phenotypes with the risk of overall and site-specific cancers. METHODS: We derived four distinct body shape phenotypes from principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). The study included 340,152 men and women from 9 European countries, aged mostly 35-65 years at recruitment (1990-2000) in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 15.3 years, 47,110 incident cancer cases were recorded. PC1 (overall adiposity) was positively associated with the risk of overall cancer, with a HR per 1 standard deviation (SD) increment equal to 1.07 (95% confidence interval 1.05 to 1.08). Positive associations were observed with 10 cancer types, with HRs (per 1 SD) ranging from 1.36 (1.30-1.42) for endometrial cancer to 1.08 (1.03-1.13) for rectal cancer. PC2 (tall stature with low WHR) was positively associated with the risk of overall cancer (1.03; 1.02-1.04) and five cancer types which were not associated with PC1. PC3 (tall stature with high WHR) was positively associated with the risk of overall cancer (1.04; 1.03-1.05) and 12 cancer types. PC4 (high BMI and weight with low WC and HC) was not associated with overall risk of cancer (1.00; 0.99-1.01). CONCLUSIONS: In this multi-national study, distinct body shape phenotypes were positively associated with the incidence of 17 different cancers and overall cancer.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36477484

RESUMO

CONTEXT: The relationship between DHEAS and mortality is of scientific and public health interest, yet remains poorly understood. OBJECTIVE: Examine the association between DHEAS and cancer, cardiovascular and all-cause mortality in middle-aged and older men and women. DESIGN: Case-cohort nested within EPIC-Heidelberg. DHEAS was measured in 7,370 stored serum collected from 1994 to 1998. Median follow-up for incident mortality events: 17.7 years. SETTING: General community. PARTICIPANTS: The case-cohort included 7,370 men (mean age = 55.0) and women (mean age = 52.4 years). All deaths due to cancer (n = 1040), cardiovascular diseases (n = 598) and all causes (n = 2407) which occurred in EPIC-Heidelberg until end of 2014 were included. RESULTS: The association between DHEAS and mortality was non-linear such that both participants in the lowest (Q1) and highest (Q5) sex- and 5-year age-group specific quintiles of DHEAS were at increased hazards of mortality from cardiovascular [Q1: HR = 1.83 95%CI: (1.33-2.51), Q5: 1.39 (1.00-1.94)], cancer [Q1: 1.27 (1.01-1.60), Q5: 1.27 (1.02-1.60)] and all causes [Q1: 1.51 (1.25-1.82), Q5: 1.31 (1.08-1.58)], compared to participants in Q3. In men and women with below median DHEAS levels, doubling of DHEAS was associated with lower hazards of cardiovascular [0.87, (0.78-0.96)], cancer [0.90, (0.83-0.97)], and total mortality [0.89, (0.83-0.95)]. In contrast, a doubling in DHEAS among participants with above median levels was associated with 1.20, (1.01-1.42), 1.28, (1.01-1.62) and 1.19 (1.03-1.37) higher hazards of mortality from cancer, cardiovascular, and all-causes respectively. CONCLUSION: In this large population based study, DHEAS showed a J-shaped association with mortality. Both participants with lowest and highest levels experienced higher hazards of mortality from cancer, cardiovascular and all causes.

7.
Clin Chem Lab Med ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36342239

RESUMO

OBJECTIVES: Oxysterols, a family of oxidized cholesterol derivates, are of increasing interest due to their role in cancer development and progression. Some oxysterols are estrogen receptor modulators and thus of particular interest in breast cancer research. In human studies, two forms of circulating oxysterols are commonly evaluated: "free" (unesterified) and "total" (esterified and unesterified). However, associations between free and total oxysterols are not well established. We addressed this knowledge gap in a pilot study by evaluating correlations between the free and the total form of each of the circulating oxysterols (free vs. total), and pairwise associations within the panel of total oxysterols (total vs. total) and the panel of free oxysterols (free vs. free). METHODS: Concentrations of oxysterols and other non-cholesterol sterols were quantified in blood samples of 27 breast cancer patients from the MARIE breast cancer patient cohort using liquid chromatography mass spectrometry. We used Spearman rank correlations to assess associations. Overall, 12 oxysterols (including 27-hydroxycholesterol (HC), 25-HC, 24S-HC, 7a-HC, 5a6a-epoxycholesterol) and five sterols (including lanosterol and desmosterol) were analyzed. RESULTS: Strong correlations (r≥0.82) were observed for seven circulating free and total oxysterols/sterols. The free and total form of 27-HC (r=0.63), 25-HC (r=0.54), and two more oxysterols were weaker correlated. Correlation patterns in the panel of total oxysterols/sterols and the panel of free oxysterols/sterols were similar. CONCLUSIONS: These findings demonstrate that concentrations of most free and total oxysterols/sterols are strongly correlated. We provide further insight into the interrelationships between oxysterols in breast cancer patients.

8.
Cancers (Basel) ; 14(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36428592

RESUMO

Resistin is a polypeptide implicated in inflammatory processes, and as such could be linked to colorectal carcinogenesis. In case-control studies, higher resistin levels have been found in colorectal cancer (CRC) patients compared to healthy individuals. However, evidence for the association between pre-diagnostic resistin and CRC risk is scarce. We investigated pre-diagnostic resistin concentrations and CRC risk within the European Prospective Investigation into Cancer and Nutrition using a nested case-control study among 1293 incident CRC-diagnosed cases and 1293 incidence density-matched controls. Conditional logistic regression models controlled for matching factors (age, sex, study center, fasting status, and women-related factors in women) and potential confounders (education, dietary and lifestyle factors, body mass index (BMI), BMI-adjusted waist circumference residuals) were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for CRC. Higher circulating resistin concentrations were not associated with CRC (RR per doubling resistin, 1.11; 95% CI 0.94-1.30; p = 0.22). There were also no associations with CRC subgroups defined by tumor subsite or sex. However, resistin was marginally associated with a higher CRC risk among participants followed-up maximally two years, but not among those followed-up after more than two years. We observed no substantial correlation between baseline circulating resistin concentrations and adiposity measures (BMI, waist circumference), adipokines (adiponectin, leptin), or metabolic and inflammatory biomarkers (C-reactive protein, C-peptide, high-density lipoprotein cholesterol, reactive oxygen metabolites) among controls. In this large-scale prospective cohort, there was little evidence of an association between baseline circulating resistin concentrations and CRC risk in European men and women.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36306379

RESUMO

BACKGROUND: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand if the observed associations might be partially explained by lifestyle behaviors. METHODS: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level (measured through the Relative Index of Inequality (RII)) on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). RESULTS: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared to more educated participants. Mediation analyses showed that portions of the total effect of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). CONCLUSIONS: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. IMPACT: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population.

10.
Circulation ; 146(20): 1507-1517, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36314129

RESUMO

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.


Assuntos
Doenças Cardiovasculares , Doença das Coronárias , Diabetes Mellitus , Acidente Vascular Cerebral , Humanos , Análise da Randomização Mendeliana/métodos , Estudos Prospectivos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Doença das Coronárias/genética , Fatores de Risco , Diabetes Mellitus/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Rim
11.
Transl Lung Cancer Res ; 11(9): 1896-1911, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36248328

RESUMO

Background: Lung cancer screening may provide a favorable opportunity for a spirometry examination, to diagnose participants with undiagnosed lung function impairments, or to improve targeting of computed tomography (CT) screening intensity in view of expected net benefit. Methods: Spirometry was performed in the CT screening arm (n=2,029) of the German Lung Cancer Screening Intervention Study (LUSI)-a trial examining the effects of annual CT screening on lung cancer mortality, in 50-69-year-old long-term smokers. Participants were classified as having chronic obstructive pulmonary disease (COPD) [forced expiration in one second (FEV1)/forced vital lung capacity (FVC) <0.7], preserved ratio impaired spirometry (PRISm; FEV1/FVC ≥0.7 and FEV1% predicted <80%), or normal spirometry. Descriptive statistics were used to examine associations of COPD or PRISm with respiratory symptoms, and self-reported medical diagnoses of respiratory and other morbidities. Logistic regression and proportional hazards regression were used to examine associations of COPD and PRISm, as well as their self-reported medical diagnoses, with risks of lung cancer and all-cause mortality. Results: A total of 1,987 screening arm participants (98%) provided interpretable spirometry measurements; of these, 34.3% had spirometric patterns consistent with either COPD (18.6%) or PRISm (15.7%). Two thirds of participants with COPD or PRISm were asymptomatic, and only 23% reported a previous medical diagnosis concordant with COPD. Participants reporting a diagnosis tended to be more often current and heavier smokers, and more often had respiratory symptoms, cardiovascular comorbidities, or more severe lung function impairments. Independently of smoking history, moderate-to-severe (GOLD 2-4) COPD (OR =2.14; 95% CI: 1.54-2.98), and PRISm (OR =2.68; 95% CI: 1.61-4.40), were associated with increased lung cancer risk. Lung cancer patients with PRISm less frequently had adenocarcinomas, and more often squamous cell or small cell tumors, compared to those with normal spirometry (n=45), and both PRISm and COPD were associated with more advanced lung cancer tumor stage for screen-detected cancers. PRISm and COPD, depending on GOLD stage, were also associated with about 2- to 4-fold increases in risk of overall mortality, which to 87 percent had causes other than lung cancer. Conclusions: About one third of smokers eligible for lung cancer screening in Germany have COPD or PRISm. As these conditions were associated with detection of lung cancer, spirometry may help identify populations at high risk for death of lung cancer or other causes, and who might particularly benefit from CT screening.

12.
Eur J Epidemiol ; 37(10): 1107-1124, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36260190

RESUMO

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19-74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2-3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4-5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years.


Assuntos
Estudos Prospectivos , Masculino , Humanos , Feminino , Estudos de Coortes , Alemanha/epidemiologia , Inquéritos e Questionários , Autorrelato
13.
Am J Gastroenterol ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36227801

RESUMO

INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort. METHODS: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

14.
Front Physiol ; 13: 976949, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203934

RESUMO

Obesity-related metabolic disorders such as hypertension, hyperlipidemia and chronic inflammation have been associated with aortic dilatation and resulting in aortic aneurysms in many cases. Whether weight loss may reduce the risk of aortic dilatation is not clear. In this study, the diameter of the descending thoracic aorta, infrarenal abdominal aorta and aortic bifurcation of 144 overweight or obese non-smoking adults were measured by MR-imaging, at baseline, and 12 and 50 weeks after weight loss by calorie restriction. Changes in aortic diameter, anthropometric measures and body composition and metabolic markers were evaluated using linear mixed models. The association of the aortic diameters with the aforementioned clinical parameters was analyzed using Spearman`s correlation. Weight loss was associated with a reduction in the thoracic and abdominal aortic diameters 12 weeks after weight loss (predicted relative differences for Quartile 4: 2.5% ± 0.5 and -2.2% ± 0.8, p < 0.031; respectively). Furthermore, there was a nominal reduction in aortic diameters during the 50-weeks follow-up period. Aortic diameters were positively associated with weight, visceral adipose tissue, glucose, HbA1c and with both systolic and diastolic blood pressure. Weight loss induced by calorie restriction may reduce aortic diameters. Future studies are needed to investigate, whether the reduction of aortic diameters via calorie restriction may help to prevent aortic aneurysms.

15.
Cancer Res Commun ; 2(4): 211-219, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36303815

RESUMO

Background: Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene-environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this. Methods: We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P<0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test. Results: After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE=4.44×10-6). Conclusion: In this transcriptome-informed genome-wide gene-environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk. Impact: Our study suggests a limited role of gene-environment interactions in breast cancer risk.

16.
Int J Cancer ; 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36305647

RESUMO

The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI: 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6-14) and overall specificity was 92% (95% CI: 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2-32.1) in subjects with blood drawn up to 1 year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36243353

RESUMO

BACKGROUND & AIMS: Industrial foods have been associated with increased risks of several chronic conditions. We investigated the relationship between the degree of food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC) in the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Analyses included 413,590 participants (68.6% women; mean baseline age, 51.7 y) from 8 European countries. Dietary data were collected at baseline from validated country-specific dietary questionnaires. Associations between proportions of unprocessed/minimally processed and ultraprocessed food intake and CD and UC risks were estimated using Cox models to obtain hazard ratios (HRs) and 95% CIs. Models were stratified by center, age, and sex, and adjusted for smoking status, body mass index, physical activity, energy intake, educational level, and alcohol consumption. RESULTS: During a mean follow-up period of 13.2 years, 179 incident cases of CD and 431 incident cases of UC were identified. The risk of CD was lower in people consuming high proportions of unprocessed/minimally processed foods (adjusted HR for the highest vs lowest quartile: 0.57; 95% CI, 0.35-0.93; P trend < .01), particularly fruits and vegetables (adjusted HRs, 0.54; 95% CI, 0.34-0.87 and 0.55; 95% CI, 0.34-0.91, respectively). There was no association between unprocessed/minimally processed food intake and the risk of UC. No association was detected between ultraprocessed food consumption and CD or UC risks. CONCLUSIONS: In the European Prospective Investigation into Cancer and Nutrition cohort, consumption of unprocessed/minimally processed foods was associated with a lower risk of CD. No association between UC risk and food processing was found.

18.
BMC Med ; 20(1): 351, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36258205

RESUMO

BACKGROUND: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. METHODS: We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. RESULTS: Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. CONCLUSIONS: These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Estudos Prospectivos , Esfingomielinas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Lisofosfatidilcolinas , Glutamina , Histidina , Fatores de Risco , Estudos de Casos e Controles , Fosfatidilcolinas , Prolina
19.
Int J Cancer ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36121664

RESUMO

PROBASE is a population-based, randomized trial of 46 495 German men recruited at age 45 to compare effects of risk-adapted prostate cancer (PCa) screening starting either immediately at age 45, or at a deferred age of 50 years. Based on prostate-specific antigen (PSA) levels, men are classified into risk groups with different screening intervals: low-risk (<1.5 ng/ml, 5-yearly screening), intermediate-risk (1.5-2.99 ng/ml, 2 yearly), and high risk (>3 ng/ml, recommendation for immediate biopsy). Over the first 6 years of study participation, attendance rates to scheduled screening visits varied from 70.5% to 79.4%, depending on the study arm and risk group allocation, in addition 11.2% to 25.4% of men reported self-initiated PSA tests outside the PROBASE protocol. 38.5% of participants had a history of digital rectal examination or PSA testing prior to recruitment to PROBASE, frequently associated with family history of PCa. These men showed higher rates (33% to 57%, depending on subgroups) of self-initiated PSA testing in-between PROBASE screening rounds. In the high-risk groups (both arms), the biopsy acceptance rate was 64% overall, but was higher among men with screening PSA ≥4 ng/ml (>71%) and with PIRADS ≥3 findings upon multiparameter magnetic resonance imaging (mpMRI) (>72%), compared with men with PSA ≥3 to 4 ng/ml (57%) or PIRADS score ≤ 2 (59%). Overall, PROBASE shows good acceptance of a risk-adapted PCa screening strategy in Germany. Implementation of such a strategy should be accompanied by a well-structured communication, to explain not only the benefits but also the harms of PSA screening.

20.
Cancer Med ; 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36148781

RESUMO

BACKGROUND: The association between protein intake and prostate cancer risk remains unclear. AIMS: To prospectively investigate the associations of dietary intakes of total protein, protein from different dietary sources, and amino acids with prostate cancer risk and mortality. METHODS: In 131,425 men from the European Prospective Investigation into Cancer and Nutrition, protein and amino acid intakes were estimated using validated dietary questionnaires. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a mean follow-up of 14.2 years, 6939 men were diagnosed with prostate cancer and 914 died of the disease. Dairy protein was positively associated with overall prostate cancer risk in the three highest fifths compared to the lowest (HRQ3 =1.14 (95% CI 1.05-1.23); HRQ 4=1.09 (1.01-1.18); HRQ5 =1.10 (1.02-1.19)); similar results were observed for yogurt protein (HRQ3 =1.14 (1.05-1.24); HRQ4 =1.09 (1.01-1.18); HRQ5 =1.12 (1.04-1.21)). For egg protein intake and prostate cancer mortality, no association was observed by fifths, but there was suggestive evidence of a positive association in the analysis per standard deviation increment. There was no strong evidence of associations with different tumour subtypes. DISCUSSION: Considering the weak associations and many tests, the results must be interpreted with caution. CONCLUSION: This study does not provide strong evidence for an association of intakes of total protein, protein from different dietary sources or amino acids with prostate cancer risk or mortality. However, our results may suggest some weak positive associations, which need to be confirmed in large-scale, pooled analyses of prospective data.

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