| 1. |
|
|
| 2. |
- Menkveld, Albert J., et al.
(författare)
-
Nonstandard Errors
- 2024
-
Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
|
|
| 3. |
- Aleksandrova, Krasimira, et al.
(författare)
-
Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study
- 2014
-
Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 134:3, s. 612-621
-
Tidskriftsartikel (refereegranskat)abstract
- Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.
|
|
| 4. |
- Aleksandrova, Krasimira, et al.
(författare)
-
Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer : results from the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2014
-
Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 29:4, s. 261-275
-
Tidskriftsartikel (refereegranskat)abstract
- A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.
|
|
| 5. |
- Aleksandrova, Krasimira, et al.
(författare)
-
Circulating C-reactive protein concentrations and risks of colon and rectal cancer : a nested case-control study within the European Prospective Investigation into Cancer and Nutrition
- 2010
-
Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 172:4, s. 407-418
-
Tidskriftsartikel (refereegranskat)abstract
- The authors investigated associations between serum C-reactive protein (CRP) concentrations and colon and rectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (1992-2003) among 1,096 incident cases and 1,096 controls selected using risk-set sampling and matched on study center, age, sex, time of blood collection, fasting status, menopausal status, menstrual cycle phase, and hormone replacement therapy. In conditional logistic regression with adjustment for education, smoking, nutritional factors, body mass index, and waist circumference, CRP showed a significant nonlinear association with colon cancer risk but not rectal cancer risk. Multivariable-adjusted relative risks for CRP concentrations of > or = 3.0 mg/L versus <1.0 mg/L were 1.36 (95% confidence interval (CI): 1.00, 1.85; P-trend = 0.01) for colon cancer and 1.02 (95% CI: 0.67, 1.57; P-trend = 0.65) for rectal cancer. Colon cancer risk was significantly increased in men (relative risk = 1.74, 95% CI: 1.11, 2.73; P-trend = 0.01) but not in women (relative risk = 1.06, 95% CI: 0.67, 1.68; P-trend = 0.13). Additional adjustment for C-peptide, glycated hemoglobin, and high density lipoprotein cholesterol did not attenuate these results. These data provide evidence that elevated CRP concentrations are related to a higher risk of colon cancer but not rectal cancer, predominantly among men and independently of obesity, insulin resistance, and dyslipidemia.
|
|
| 6. |
- Aleksandrova, Krasimira, et al.
(författare)
-
Combined impact of healthy lifestyle factors on colorectal cancer : a large European cohort study
- 2014
-
Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 12:1, s. 168-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.
|
|
| 7. |
- Aleksandrova, Krasimira, et al.
(författare)
-
Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer
- 2014
-
Ingår i: Hepatology. - : Wiley-Blackwell. - 0270-9139 .- 1527-3350. ; 60:3, s. 858-871
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137) or IBD (n=34). Using risk set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total, high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured and incidence rate ratios (IRRs) and 95% confidence intervals (CI-s) estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection and adiposity measures, higher concentrations of CRP, IL-6, C-peptide and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95%CI = 1.02-1.46, P=0.03; 1.90; 95%CI = 1.30-2.77, P=0.001; 2.25; 95%CI = 1.43-3.54, P=0.0005 and 2.09; 95%CI = 1.19-3.67, P=0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95%CI = 1.05-1.42, P=0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95%CI = 1.25-2.11, P=0.0003) and IBD (IRR = 10.5; 95%CI = 2.20-50.90, P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide and non-HMW adiponectin, and 0.46 for GLDH indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.
|
|
| 8. |
- Aleksandrova, Krasimira, et al.
(författare)
-
Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into Cancer and nutrition cohort
- 2012
-
Ingår i: Cancer Research. - Philadelphia, USA : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 72:20, s. 5328-5337
-
Tidskriftsartikel (refereegranskat)abstract
- Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; P-trend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, P-trend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P-trend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, P-trend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis. Cancer Res; 72(20); 5328-37. (C) 2012 AACR.
|
|
| 9. |
- Aleksandrova, Krasimira, et al.
(författare)
-
Metabolic syndrome and risks of colon and rectal cancer : the European prospective investigation into cancer and nutrition study.
- 2011
-
Ingår i: Cancer prevention research (Philadelphia, Pa.). - 1940-6215. ; 4:11, s. 1873-83
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolic syndrome (MetS) is purportedly related to risk of developing colorectal cancer; however, the association of MetS, as defined according to recent international criteria, and colorectal cancer has not been yet evaluated. In particular, it remains unclear to what extent the MetS components individually account for such an association. We addressed these issues in a nested case-control study that included 1,093 incident cases matched (1:1) to controls by using incidence density sampling. Conditional logistic regression was used to estimate relative risks (RR) and 95% CIs. MetS was defined according to the criteria of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII), the International Diabetes Federation (IDF), and the 2009 harmonized definition. Among individual components, abdominal obesity (RR = 1.51; 95% CI: 1.16-1.96) was associated with colon cancer, whereas abnormal glucose metabolism was associated with both colon (RR = 2.05; 95% CI: 1.57-2.68) and rectal cancer (RR = 2.07; 95% CI: 1.45-2.96). MetS, as defined by each of the definitions, was similarly associated with colon cancer (e.g., RR = 1.91; 95% CI: 1.47-2.42 for MetS by NCEP/ATPIII), whereas MetS by NCEP/ATPIII, but not IDF or harmonized definition, was associated with rectal cancer (RR = 1.45; 95% CI: 1.02-2.06). Overall, these associations were stronger in women than in men. However, the association between MetS and colorectal cancer was accounted for by abdominal obesity and abnormal glucose metabolism such that MetS did not provide risk information beyond these components (likelihood ratio test P = 0.10 for MetS by NCEP/ATPIII). These data suggest that simple assessment of abnormal glucose metabolism and/or abdominal obesity to identify individuals at colorectal cancer risk may have higher clinical utility than applying more complex MetS definitions. Cancer Prev Res; 4(11); 1873-83. ©2011 AACR.
|
|
| 10. |
- Aleksandrova, Krasimira, et al.
(författare)
-
Physical activity, mediating factors and risk of colon cancer : insights into adiposity and circulating biomarkers from the EPIC cohort
- 2017
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 46:6, s. 1823-1835
-
Tidskriftsartikel (refereegranskat)abstract
- There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer. We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline. High physical activity was associated with a lower risk of colon cancer: relative risk a parts per thousand91 MET-h/week vs < 91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively. Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.
|
|
| 11. |
- Aleksandrova, Krasimira, et al.
(författare)
-
Total and high-molecular-weight adiponectin and risk of colorectal cancer : the European prospective investigation into cancer and nutrition study
- 2012
-
Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 33:6, s. 1211-1218
-
Tidskriftsartikel (refereegranskat)abstract
- Adiponectin - an adipose-tissue-derived protein may provide a molecular link between obesity and colorectal cancer (CRC), but evidence from large prospective studies is limited. In particular, no epidemiological study explored high-molecular-weight (HMW) and non-HMW adiponectin fractions in relation to CRC risk, despite they were hypothesised to have differential biological activities, i.e. regulating insulin sensitivity (HMW-adiponectin) versus inflammatory response (non-HMW-adiponectin). In a prospective nested case-control study we investigated whether pre-diagnostic serum concentrations of total, HMW and non-HMW-adiponectin are associated with risk of CRC, independent of obesity and other known CRC risk factors. A total of 1206 incident cases (755 colon, 451 rectal) were matched to 1206 controls using incidence density sampling. In conditional logistic regression, adjusted for dietary and lifestyle factors, total adiponectin and non-HMW-adiponectin concentrations were inversely associated with risk of CRC [relative risk (RR) comparing highest versus lowest quintile = 0.71, 95% confidence interval (CI) = 0.53-0.95, P (trend)=0.03 for total adiponectin and 0.45, 95%CI=0.34-0.61, P (trend)<0.0001 for non-HMW-adiponectin]. HMW-adiponectin concentrations were not associated with CRC risk (RR=0.91, 95%CI=0.68-1.22, P (trend)=0.55). Non-HMW-adiponectin was associated with CRC risk even after adjustment for body mass index and waist circumference (RR=0.39, 95%CI=0.26-0.60, P (trend)<0.0001); whereas the association with total adiponectin was no longer significant (RR=0.81, 95%CI=0.60-1.09, P (trend)=0.23). When stratified by cancer site, non-HMW-adiponectin was inversely associated with both colon and rectal cancer. These findings suggest an important role of the relative proportion of non-HMW-adiponectin in CRC pathogenesis. Future studies are warranted to confirm these results and to elucidate the underlying mechanisms.
|
|
| 12. |
- Armstrong, Ben, et al.
(författare)
-
The Role of Humidity in Associations of High Temperature with Mortality : A Multicountry, Multicity Study
- 2019
-
Ingår i: Journal of Environmental Health Perspectives. - : The National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 127:9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is strong experimental evidence that physiologic stress from high temperatures is greater if humidity is higher. However, heat indices developed to allow for this have not consistently predicted mortality better than dry-bulb temperature.Objectives: We aimed to clarify the potential contribution of humidity an addition to temperature in predicting daily mortality in summer by using a large multicountry dataset.Methods: In 445 cities in 24 countries, we fit a time-series regression model for summer mortality with a distributed lag nonlinear model (DLNM) for temperature (up to lag 3) and supplemented this with a range of terms for relative humidity (RH) and its interaction with temperature. City-specific associations were summarized using meta-analytic techniques.Results: Adding a linear term for RH to the temperature term improved fit slightly, with an increase of 23% in RH (the 99th percentile anomaly) associated with a 1.1% [95% confidence interval (CI): 0.8, 1.3] decrease in mortality. Allowing curvature in the RH term or adding terms for interaction of RH with temperature did not improve the model fit. The humidity-related decreased risk was made up of a positive coefficient at lag 0 outweighed by negative coefficients at lags of 1–3 d. Key results were broadly robust to small model changes and replacing RH with absolute measures of humidity. Replacing temperature with apparent temperature, a metric combining humidity and temperature, reduced goodness of fit slightly.Discussion:The absence of a positive association of humidity with mortality in summer in this large multinational study is counter to expectations from physiologic studies, though consistent with previous epidemiologic studies finding little evidence for improved prediction by heat indices. The result that there was a small negative average association of humidity with mortality should be interpreted cautiously; the lag structure has unclear interpretation and suggests the need for future work to clarify.
|
|
| 13. |
- Arslan, Alan A., et al.
(författare)
-
Anthropometric Measures, Body Mass Index, and Pancreatic Cancer A Pooled Analysis From the Pancreatic Cancer Cohort Consortium (PanScan)
- 2010
-
Ingår i: Archives of Internal Medicine. - 0003-9926. ; 170:9, s. 791-802
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity has been proposed as a risk factor for pancreatic cancer. Methods: Pooled data were analyzed from the National Cancer Institute Pancreatic Cancer Cohort Consortium (PanScan) to study the association, between prediagnostic anthropometric measures and risk of pancreatic cancer. PanScan applied a nested case-control study design and included 2170 cases and 2209 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression for cohort-specific quartiles of body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), weight, height, waist circumference, and waist to hip ratio as well as conventional BMI categories (underweight, <18.5; normal weight, 18.5-24.9; overweight, 25.0-29.9; obese, 30.0-34.9; and severely obese, >= 35.0). Models were adjusted for potential confounders. Results: In all of the participants, a positive association between increasing BMI and risk of pancreatic cancer was observed (adjusted OR for the highest vs lowest BMI guartile, 1.33; 95% Cl, 1.12-1.58; P-trend<.001). In men, the adjusted OR for pancreatic cancer for the highest vs lowest quartile of BMI was 1.33 (95% Cl, 1.04-1.69; P-trend<.03), and in women it was 1.34 (95% Cl, 1.05-1.70; P-trend=.01). Increased waist to hip ratio was associated with increased risk of pancreatic cancer in women (adjusted OR for the highest vs lowest quartile, 1.87; 95% Cl, 1.31-2.69; P-trend=.003) but less so in men. Conclusions: These findings provide strong support for a positive association between BMI and pancreatic cancer risk. In addition, centralized fat distribution may increase pancreatic cancer risk, especially in women. Arch Intern Med. 2010;170(9):791 -802
|
|
| 14. |
- Campa, Daniele, et al.
(författare)
-
Genetic variability of the mTOR pathway and prostate cancer risk in the European prospective investigation on cancer (EPIC)
- 2011
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2, s. e16914-
-
Tidskriftsartikel (refereegranskat)abstract
- The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p<0.01) and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (OR(allele) = 0.85, 95% CI 0.78-0.94, p = 1.3×10(-3) for rs546950 and OR(allele) = 0.84, 95% CI 0.76-0.93, p = 5.6×10(-4) for rs4955720). We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.
|
|
| 15. |
- Chen, Gongbo, et al.
(författare)
-
All-cause, cardiovascular, and respiratory mortality and wildfire-related ozone : a multicountry two-stage time series analysis
- 2024
-
Ingår i: The Lancet Planetary Health. - : Elsevier. - 2542-5196. ; 8:7, s. e452-e462
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Wildfire activity is an important source of tropospheric ozone (O3) pollution. However, no study to date has systematically examined the associations of wildfire-related O3 exposure with mortality globally.Methods: We did a multicountry two-stage time series analysis. From the Multi-City Multi-Country (MCC) Collaborative Research Network, data on daily all-cause, cardiovascular, and respiratory deaths were obtained from 749 locations in 43 countries or areas, representing overlapping periods from Jan 1, 2000, to Dec 31, 2016. We estimated the daily concentration of wildfire-related O3 in study locations using a chemical transport model, and then calibrated and downscaled O3 estimates to a resolution of 0·25° × 0·25° (approximately 28 km2 at the equator). Using a random-effects meta-analysis, we examined the associations of short-term wildfire-related O3 exposure (lag period of 0–2 days) with daily mortality, first at the location level and then pooled at the country, regional, and global levels. Annual excess mortality fraction in each location attributable to wildfire-related O3 was calculated with pooled effect estimates and used to obtain excess mortality fractions at country, regional, and global levels.Findings: Between 2000 and 2016, the highest maximum daily wildfire-related O3 concentrations (≥30 μg/m3) were observed in locations in South America, central America, and southeastern Asia, and the country of South Africa. Across all locations, an increase of 1 μg/m3 in the mean daily concentration of wildfire-related O3 during lag 0–2 days was associated with increases of 0·55% (95% CI 0·29 to 0·80) in daily all-cause mortality, 0·44% (–0·10 to 0·99) in daily cardiovascular mortality, and 0·82% (0·18 to 1·47) in daily respiratory mortality. The associations of daily mortality rates with wildfire-related O3 exposure showed substantial geographical heterogeneity at the country and regional levels. Across all locations, estimated annual excess mortality fractions of 0·58% (95% CI 0·31 to 0·85; 31 606 deaths [95% CI 17 038 to 46 027]) for all-cause mortality, 0·41% (–0·10 to 0·91; 5249 [–1244 to 11 620]) for cardiovascular mortality, and 0·86% (0·18 to 1·51; 4657 [999 to 8206]) for respiratory mortality were attributable to short-term exposure to wildfire-related O3.Interpretation: In this study, we observed an increase in all-cause and respiratory mortality associated with short-term wildfire-related O3 exposure. Effective risk and smoke management strategies should be implemented to protect the public from the impacts of wildfires.
|
|
| 16. |
- Chen, Gongbo, et al.
(författare)
-
Mortality risk attributable to wildfire-related PM2·5 pollution : a global time series study in 749 locations
- 2021
-
Ingår i: The Lancet Planetary Health. - : Elsevier. - 2542-5196. ; 5:9, s. e579-e587
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2·5 and mortality across various regions of the world.METHODS: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM2·5 exposure was calculated.FINDINGS: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m3 increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM2·5 exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM2·5 exposure during the study period.INTERPRETATION: Short-term exposure to wildfire-related PM2·5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires.
|
|
| 17. |
- Chen, Kai, et al.
(författare)
-
Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities
- 2021
-
Ingår i: The Lancet Planetary Health. - 2542-5196. ; 5:4, s. e191-e199
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological evidence on short-term association between ambient carbon monoxide (CO) and mortality is inconclusive and limited to single cities, regions, or countries. Generalisation of results from previous studies is hindered by potential publication bias and different modelling approaches. We therefore assessed the association between short-term exposure to ambient CO and daily mortality in a multicity, multicountry setting. Methods: We collected daily data on air pollution, meteorology, and total mortality from 337 cities in 18 countries or regions, covering various periods from 1979 to 2016. All included cities had at least 2 years of both CO and mortality data. We estimated city-specific associations using confounder-adjusted generalised additive models with a quasi-Poisson distribution, and then pooled the estimates, accounting for their statistical uncertainty, using a random-effects multilevel meta-analytical model. We also assessed the overall shape of the exposure–response curve and evaluated the possibility of a threshold below which health is not affected. Findings: Overall, a 1 mg/m3 increase in the average CO concentration of the previous day was associated with a 0·91% (95% CI 0·32–1·50) increase in daily total mortality. The pooled exposure–response curve showed a continuously elevated mortality risk with increasing CO concentrations, suggesting no threshold. The exposure–response curve was steeper at daily CO levels lower than 1 mg/m3, indicating greater risk of mortality per increment in CO exposure, and persisted at daily concentrations as low as 0·6 mg/m3 or less. The association remained similar after adjustment for ozone but was attenuated after adjustment for particulate matter or sulphur dioxide, or even reduced to null after adjustment for nitrogen dioxide. Interpretation: This international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants. Funding: EU Horizon 2020, UK Medical Research Council, and Natural Environment Research Council.
|
|
| 18. |
- Choi, Hayon Michelle, et al.
(författare)
-
Effect modification of greenness on the association between heat and mortality : A multi-city multi-country study
- 2022
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 84
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Identifying how greenspace impacts the temperature-mortality relationship in urban environments is crucial, especially given climate change and rapid urbanization. However, the effect modification of greenspace on heat-related mortality has been typically focused on a localized area or single country. This study examined the heat-mortality relationship among different greenspace levels in a global setting.METHODS: We collected daily ambient temperature and mortality data for 452 locations in 24 countries and used Enhanced Vegetation Index (EVI) as the greenspace measurement. We used distributed lag non-linear model to estimate the heat-mortality relationship in each city and the estimates were pooled adjusting for city-specific average temperature, city-specific temperature range, city-specific population density, and gross domestic product (GDP). The effect modification of greenspace was evaluated by comparing the heat-related mortality risk for different greenspace groups (low, medium, and high), which were divided into terciles among 452 locations.FINDINGS: Cities with high greenspace value had the lowest heat-mortality relative risk of 1·19 (95% CI: 1·13, 1·25), while the heat-related relative risk was 1·46 (95% CI: 1·31, 1·62) for cities with low greenspace when comparing the 99th temperature and the minimum mortality temperature. A 20% increase of greenspace is associated with a 9·02% (95% CI: 8·88, 9·16) decrease in the heat-related attributable fraction, and if this association is causal (which is not within the scope of this study to assess), such a reduction could save approximately 933 excess deaths per year in 24 countries.INTERPRETATION: Our findings can inform communities on the potential health benefits of greenspaces in the urban environment and mitigation measures regarding the impacts of climate change.FUNDING: This publication was developed under Assistance Agreement No. RD83587101 awarded by the U.S. Environmental Protection Agency to Yale University. It has not been formally reviewed by EPA. The views expressed in this document are solely those of the authors and do not necessarily reflect those of the Agency. EPA does not endorse any products or commercial services mentioned in this publication. Research reported in this publication was also supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number R01MD012769. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Also, this work has been supported by the National Research Foundation of Korea (2021R1A6A3A03038675), Medical Research Council-UK (MR/V034162/1 and MR/R013349/1), Natural Environment Research Council UK (Grant ID: NE/R009384/1), Academy of Finland (Grant ID: 310372), European Union's Horizon 2020 Project Exhaustion (Grant ID: 820655 and 874990), Czech Science Foundation (22-24920S), Emory University's NIEHS-funded HERCULES Center (Grant ID: P30ES019776), and Grant CEX2018-000794-S funded by MCIN/AEI/ 10.13039/501100011033 The funders had no role in the design, data collection, analysis, interpretation of results, manuscript writing, or decision to publication.
|
|
| 19. |
- Christakoudi, Sofia, et al.
(författare)
-
A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity : results from a large European cohort
- 2020
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
|
|
| 20. |
- Chuang, Shu-Chun, et al.
(författare)
-
Cellular immune activity biomarker neopterin is associated hyperlipidemia : results from a large population-based study
- 2016
-
Ingår i: Immunity & Ageing. - : Springer Science and Business Media LLC. - 1742-4933. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Increased serum neopterin had been described in older age two decades ago. Neopterin is a biomarker of systemic adaptive immune activation that could be potentially implicated in metabolic syndrome (MetS). Measurements of waist circumference, triglycerides, high-density lipoprotein cholesterol (HDLC), systolic and diastolic blood pressure, glycated hemoglobin as components of MetS definition, and plasma total neopterin concentrations were performed in 594 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC).Results: Higher total neopterin concentrations were associated with reduced HDLC (9.7 %, p < 0.01 for men and 9.2 %, p < 0.01 for women), whereas no association was observed with the rest of the MetS components as well as with MetS overall (per 10 nmol/L: OR = 1.42, 95 % CI = 0.85-2.39 for men and OR = 1.38, 95 % CI = 0.79-2.43).Conclusions: These data suggest that high total neopterin concentrations are cross-sectionally associated with reduced HDLC, but not with overall MetS.
|
|
| 21. |
- Domingo, Nina G.G., et al.
(författare)
-
Ozone-related acute excess mortality projected to increase in the absence of climate and air quality controls consistent with the Paris Agreement
- 2024
-
Ingår i: One Earth. - : Elsevier. - 2590-3330 .- 2590-3322. ; 7:2, s. 325-335
-
Tidskriftsartikel (refereegranskat)abstract
- Short-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate.
|
|
| 22. |
- Fedirko, Veronika, et al.
(författare)
-
Pre-diagnostic anthropometry and survival after colorectal cancer diagnosis in Western European populations
- 2014
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:8, s. 1949-1960
-
Tidskriftsartikel (refereegranskat)abstract
- General and abdominal adiposity are associated with a high risk of developing colorectal cancer (CRC), but the role of these exposures on cancer survival has been less studied. The association between pre-diagnostic anthropometric characteristics and CRC-specific and all-cause death was examined among 3,924 men and women diagnosed with CRC between 1992 and 2009 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate hazard ratios (FIRS) and corresponding 95% confidence intervals (as). Over a mean follow-up period of 49 months, 1,309 deaths occurred of which 1,043 (79.7%) were due to CRC. In multivariable analysis, prediagnostic BMI kg/m2 was associated with a high risk for CRC-specific (HR = 1.26, 95% CI = 1.04-1.52) and all-cause (HR = 1.32, 95% CI = 1.12-1.56) death relative to BMI <25 kg/m(2). Every 5 kg/m(2) increase in BMI was associated with a high risk for CRC-specific (HR = 1.10, 95% CI = 1.02-1.19) and all-cause death (HR = 1.12, 95% Cl = 1.05-1.20); and every 10 cm increase in waist circumference was associated with a high risk for CRC-specific (HR = 1.09, 95% Cl = 1.02-1.16) and allcause death (HR= 1.11, 95% CI= 1.05-1.18). Similar associations were observed for waist-to-hip and waist-to-height ratios. Height was not associated with CRC-specific or all-cause death. Associations tended to be stronger among men than in women. Possible interactions by age at diagnosis, cancer stage, tumour location, and hormone replacement therapy use among postmenopausal women were noted. Pre-diagnostic general and abdominal adiposity are associated with lower survival after CRC diagnosis.
|
|
| 23. |
- Fedirko, Veronika, et al.
(författare)
-
Prediagnostic circulating parathyroid hormone concentration and colorectal cancer in the European Prospective Investigation into Cancer and Nutrition cohort
- 2011
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:5, s. 767-778
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parathyroid hormone (PTH) has been proposed to play a promoting role in carcinogenesis. However, no epidemiologic studies have yet directly investigated its role in colorectal cancer (CRC). METHODS: A case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort was conducted with 1,214 incident, sporadic CRC cases matched to 1,214 controls. Circulating prediagnostic PTH and 25-hydroxy vitamin D [25(OH)D] concentrations were measured by enzyme-linked immunosorbent assays. Detailed dietary and lifestyle questionnaire data were collected at baseline. Multivariable conditional logistic regression was used to estimate the incidence rate ratio (RR) with 95% confidence intervals (95% CI) for the association between circulating PTH and CRC risk. RESULTS: In multivariate analyses [including adjustment for 25(OH)D concentration] with a priori defined cutoff points, high levels of serum PTH (≥65 ng/L) compared with medium PTH levels of 30-65 ng/L were associated with increased CRC risk (RR = 1.41, 95% CI: 1.03-1.93). In analyses by sex, the CRC risk was 1.77 (95% CI: 1.14-2.75) and 1.15 (95% CI: 0.73-1.84) in men and women, respectively (P(heterogeneity) = 0.01). In subgroup analyses by anatomical subsite, the risk for colon cancer was RR = 1.56, 95% CI: 1.03-2.34, and for rectal cancer RR = 1.20, 95% CI: 0.72-2.01 (P(heterogeneity) = 0.21). Effect modification by various risk factors was examined. CONCLUSIONS: The results of this study suggest that high serum PTH levels may be associated with incident, sporadic CRC in Western European populations, and in particular among men. IMPACT: To our knowledge, this is the first study on PTH and CRC. The role of PTH in carcinogenesis needs to be further investigated.
|
|
| 24. |
- Friedenreich, Christine, et al.
(författare)
-
Anthropometric factors and risk of endometrial cancer: the European prospective investigation into cancer and nutrition
- 2007
-
Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 18:4, s. 399-413
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To examine the association between anthropometry and endometrial cancer, particularly by menopausal status and exogenous hormone use subgroups. Methods Among 223,008 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, there were 567 incident endometrial cancer cases during 6.4 years of follow-up. The analysis was performed with Cox proportional hazards modeling. Results Weight, body mass index (BMI), waist and hip circumferences and waist-hip ratio (WHR) were strongly associated with increased risk of endometrial cancer. The relative risk (RR) for obese (BMI 30- < 40 kg/m(2)) compared to normal weight (BMI < 25) women was 1.78, 95% CI = 1.41-2.26, and for morbidly obese women (BMI >= 40) was 3.02, 95% CI = 1.66-5.52. The RR for women with a waist circumference of >= 88 cm vs. < 80 cm was 1.76, 95% CI = 1.42-2.19. Adult weight gain of >= 20 kg compared with stable weight (+/- 3 kg) increased risk independent of body weight at age 20 (RR = 1.75, 95% CI = 1.11-2.77). These associations were generally stronger for postmenopausal than premenopausal women, and oral contraceptives never-users than ever-users, and much stronger among never-users of hormone replacement therapy compared to ever-users. Conclusion Obesity, abdominal adiposity, and adult weight gain were strongly associated with endometrial cancer risk. These associations were particularly evident among never-users of hormone replacement therapy.
|
|
| 25. |
- Friedenreich, Christine, et al.
(författare)
-
Physical activity and risk of colon and rectal cancers: The European Prospective Investigation into Cancer and Nutrition
- 2006
-
Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 15:12, s. 2398-2407
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated several aspects of the role of physical activity in colon and rectal cancer etiology that remain unclear in the European Prospective Investigation into Nutrition and Cancer. This cohort of 413,044 men and women had 1,094 cases of colon and 599 cases of rectal cancer diagnosed during an average of 6.4 years of follow-up. We analyzed baseline data on occupational, household, and recreational activity to examine associations by type of activity, tumor subsite, body mass index (BMI), and energy intake. The multivariate hazard ratio for colon cancer was 0.78 [95% confidence interval (95% CI), 0.59-1.03] among the most active participants when compared with the inactive, with evidence of a dose-response effect (P-trend = 0.04). For right-sided colon tumors, the risk was 0.65 (95% CI, 0.43-1.00) in the highest quartile of activity with evidence of a linear trend (P-trend=0.004). Active participants with a BMI under 25 had a risk of 0.63 (95% CI, 0.39-1.01) for colon cancer compared with the inactive. Finally, an interaction between BMI and activity (P-interaction=0.03) was observed for right-sided colon cancers; among moderately active and active participants with a BMI under 25, a risk of 0.38 (95% CI, 0.21-0.68) was found as compared with inactive participants with BMI > 30. No comparable decreased risks were observed for rectal cancer for any type of physical activity for any subgroup analyses or interactions considered. We found that physical activity reduced colon cancer risk, specifically for right-sided tumors and for lean participants, but not rectal cancer.
|
|
