1. |
- Almquist, Martin, et al.
(author)
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Metabolic factors and risk of thyroid cancer in the Metabolic syndrome and Cancer project (Me-Can)
- 2011
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In: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 22:5, s. 743-751
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Journal article (peer-reviewed)abstract
- Objective To investigate metabolic factors and their possible impact on risk of thyroid cancer. Methods A prospective cohort study was conducted based on seven population-based cohorts in Norway, Austria, and Sweden, in the Metabolic syndrome and Cancer project (Me-Can). Altogether 578,700 men and women with a mean age of 44.0 years at baseline were followed for on average 12.0 years. Relative risk of incident thyroid cancer was assessed by levels of BMI, blood pressure, and blood levels of glucose, cholesterol, triglycerides, and by a combined metabolic syndrome (MetS) score. Risk estimates were investigated for quintiles, and a z score distribution of exposures was analyzed using Cox proportional hazards regression. Results During follow-up, 255 women and 133 men were diagnosed with thyroid cancer. In women, there was an inverse association between glucose and thyroid cancer risk, with adjusted RR: 95% CI was 0.61 (0.41–0.90), p trend = 0.02 in the fifth versus the first quintile, and a positive association between BMI and thyroid cancer risk with a significant trend over quintiles. There was no association between the other metabolic factors, single or combined (Met-S), and thyroid cancer. Conclusion In women, BMI was positively, while blood glucose levels were inversely, associated with thyroid cancer.
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2. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - 2050-084X. ; 5
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Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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3. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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4. |
- Bjørge, Tone, et al.
(author)
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BMI and weight changes and risk of obesity-related cancers : a pooled European cohort study
- 2019
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 48:6, s. 1872-1885
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Journal article (peer-reviewed)abstract
- BACKGROUND: Obesity is an established risk factor for several cancers. Adult weight gain has been associated with increased cancer risk, but studies on timing and duration of adult weight gain are relatively scarce. We examined the impact of BMI (body mass index) and weight changes over time, as well as the timing and duration of excess weight, on obesity- and non-obesity-related cancers. METHODS: We pooled health data from six European cohorts and included 221 274 individuals with two or more height and weight measurements during 1972-2014. Several BMI and weight measures were constructed. Cancer cases were identified through linkage with national cancer registries. Hazard ratios (HRs) of cancer with 95% confidence intervals (CIs) were derived from time-dependent Cox-regression models. RESULTS: During follow-up, 27 881 cancer cases were diagnosed; 9761 were obesity-related. The HR of all obesity-related cancers increased with increasing BMI at first and last measurement, maximum BMI and longer duration of overweight (men only) and obesity. Participants who were overweight before age 40 years had an HR of obesity-related cancers of 1.16 (95% CI 1.02, 1.32) and 1.15 (95% CI 1.04, 1.27) in men and women, respectively, compared with those who were not overweight. The risk increase was particularly high for endometrial (70%), male renal-cell (58%) and male colon cancer (29%). No positive associations were seen for cancers not regarded as obesity-related. CONCLUSIONS: Adult weight gain was associated with increased risk of several major cancers. The degree, timing and duration of overweight and obesity also seemed to be important. Preventing weight gain may reduce the cancer risk.
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5. |
- Bjørge, Tone, et al.
(author)
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Metabolic risk factors and ovarian cancer in the metabolic syndrome and cancer project
- 2011
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 40:6, s. 1667-1677
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Journal article (peer-reviewed)abstract
- BACKGROUND: No studies have so far evaluated the impact of the metabolic syndrome (MetS) as an entity on ovarian cancer risk. The authors aimed to examine the association between factors in the MetS, individually and combined, and risk of ovarian cancer incidence and mortality. METHODS: Altogether, 290 000 women from Austria, Norway and Sweden were enrolled during 1974-2005, with measurements taken of height, weight, blood pressure and levels of glucose, cholesterol and triglycerides. Relative risks (RRs) of ovarian cancer were estimated using Cox regression for each MetS factor in quintiles and for standardized levels (z-scores), and for a composite z-score for the MetS. RRs were corrected for random error in measurements. RESULTS: During follow-up, 644 epithelial ovarian cancers and 388 deaths from ovarian cancer were identified. There was no overall association between MetS and ovarian cancer risk. Increasing levels of cholesterol [RR 1.52, 95% confidence interval (95% CI) 1.01-2.29, per 1-U increment of z-score] and blood pressure (RR 1.79, 95% CI 1.12-2.86) conferred, however, increased risks of mucinous and endometrioid tumours, respectively. In women below the age of 50 years, there was increased risk of ovarian cancer mortality for MetS (RR 1.52, 95% CI 1.00-2.30). Increasing levels of BMI (RR 1.17, 95% CI 1.01-1.37) conferred increased risk of ovarian cancer mortality in women above the age of 50 years. CONCLUSION: There was no overall association between MetS and ovarian cancer risk. However, increasing levels of cholesterol and blood pressure increased the risks of mucinous and endometrioid tumours, respectively. Increasing levels of BMI conferred an increased risk of ovarian cancer mortality in women above the age of 50 years.
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6. |
- Bjørge, Tone, et al.
(author)
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Metabolic syndrome and breast cancer in the me-can (metabolic syndrome and cancer) project.
- 2010
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 19:7, s. 1737-1745
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Journal article (peer-reviewed)abstract
- BACKGROUND: Few studies have assessed the metabolic syndrome (MetS) as an entity in relation to breast cancer risk, and results have been inconsistent. We aimed to examine the association between MetS factors (individually and combined) and risk of breast cancer incidence and mortality. METHODS: Two hundred ninety thousand women from Austria, Norway, and Sweden were enrolled during 1974-2005, with measurements of height, weight, blood pressure, and levels of glucose, cholesterol, and triglycerides. Relative risks (RR) of breast cancer were estimated using Cox proportional hazards regression for each MetS factor in quintiles and for standardized levels (z-scores) and for a composite z-score for the MetS. RESULTS: There were 4,862 incident cases of breast cancer and 633 deaths from breast cancer identified. In women below age 50, there was a decreased risk of incident cancer for the MetS (per 1-unit increment of z-score; RR, 0.83; 95% confidence interval, 0.76-0.90) as well as for the individual factors (except for glucose). The lowest risks were seen among the heaviest women. In women above age 60, there was an increased risk of breast cancer mortality for the MetS (RR, 1.23; 95% confidence interval, 1.04-1.45) and for blood pressure and glucose. The strongest association with mortality was seen for increased glucose concentrations. CONCLUSIONS: The MetS was associated with a decreased risk of incident breast cancer in women below age 50 with high body mass index, and with an increased risk of breast cancer mortality in women above 60. IMPACT: Lifestyle interventions as recommended for cardiovascular disease prevention may be of value to prevent breast cancer mortality in postmenopausal women.
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7. |
- Bjørge, Tone, et al.
(author)
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Metabolic syndrome and endometrial carcinoma
- 2010
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 171:8, s. 892-902
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Journal article (peer-reviewed)abstract
- The authors examined the association between the metabolic syndrome and risk of incident endometrial and fatal uterine corpus cancer within a large prospective cohort study. Approximately 290,000 women from Austria, Norway, and Sweden were enrolled during 1974-2005, with measurements of height, weight, systolic and diastolic blood pressure, and circulating levels of glucose, total cholesterol, and triglycerides. Relative risks were estimated using Cox proportional hazards regression. The metabolic syndrome was assessed as a composite z score, as the standardized sum of z scores for body mass index, blood pressure, glucose, cholesterol, and triglycerides. A total of 917 endometrial carcinomas and 129 fatal cancers were identified. Increased risks of incident endometrial carcinoma and fatal uterine corpus cancer were seen for the metabolic syndrome factors combined, as well as for individual factors (except for cholesterol). The relative risk of endometrial carcinoma for the metabolic syndrome was 1.37 (95% confidence interval: 1.28, 1.46) per 1-unit increment of z score. The positive associations between metabolic syndrome factors (both individually and combined) and endometrial carcinoma were confined to the heaviest women. The association between the metabolic syndrome and endometrial carcinoma risk seems to go beyond the risk conferred by obesity alone, particularly in women with a high body mass index.
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8. |
- Borena, Wegene, et al.
(author)
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A prospective study on metabolic risk factors and gallbladder cancer in the metabolic syndrome and cancer (Me-Can) collaborative study
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e89368-
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Journal article (peer-reviewed)abstract
- OBJECTIVE:To investigate the association between metabolic risk factors (individually and in combination) and risk of gallbladder cancer (GBC).METHODS:The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden with data on 578,700 men and women. We used Cox proportional hazard regression models to calculate relative risks of GBC by body mass index (BMI), blood pressure, and plasma levels of glucose, cholesterol, and triglycerides as continuous standardised variables and their standardised sum of metabolic syndrome (MetS) z-score. The risk estimates were corrected for random error in measurements.RESULTS:During an average follow-up of 12.0 years (SD = 7.8), 184 primary gallbladder cancers were diagnosed. Relative risk of gallbladder cancer per unit increment of z-score adjusted for age, smoking status and BMI (except for BMI itself) and stratified by birth year, sex and sub-cohorts, was for BMI 1.31 (95% confidence interval 1.11, 1.57) and blood glucose 1.76 (1.10, 2.85). Further analysis showed that the effect of BMI on GBC risk is larger among women in the premenopausal age group (1.84 (1.23, 2.78)) compared to those in the postmenopausal age group (1.29 (0.93, 1.79)). For the other metabolic factors no significant association was found (mid blood pressure 0.96 (0.71, 1.31), cholesterol 0.84 (0.66, 1.06) and serum triglycerides 1.16 (0.82, 1.64)). The relative risk per one unit increment of the MetS z-score was 1.37 (1.07, 1.73).CONCLUSION:This study showed that increasing BMI and impaired glucose metabolism pose a possible risk for gallbladder cancer. Beyond the individual factors, the results also showed that the metabolic syndrome as an entity presents a risk constellation for the occurrence of gallbladder cancer.
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9. |
- Borena, Wegene, et al.
(author)
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Long-term temporal trends in cardiovascular and metabolic risk factors
- 2009
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In: Wiener Klinische Wochenschrift. - : Springer Science and Business Media LLC. - 0043-5325 .- 1613-7671. ; 121:19-20, s. 623-630
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Metabolic factors such as obesity, hypertension, dyslipidemia and hyperglycemia have consistently been associated with increased risk of cardiovascular disease. There is also growing evidence that these factors are linked to cancer incidence and mortality. The aim of this study was to investigate long-term trends in major metabolic risk factors in three large cohorts. MATERIALS AND METHODS: Data from 239,602 individuals aged 25-64 years participating in health examinations between 1976 and 2005 were used to estimate prevalence and trends in five risk factors. RESULTS: Irrespective of geographic location, individual metabolic risk factors showed divergent trends across the observation period. Whereas obesity and hyperglycemia in men increased by a per decade ratio of 1.54 (95% CI: 1.42-1.66) and 1.62 (95% CI: 1.49-1.76), respectively, and in women by 1.48 (95% CI: 1.41-1.56) and 1.66 (95% CI: 1.57-1.75), hypertension decreased by 0.71 (95% CI: 0.68-0.74) in men and 0.83 (95% CI: 0.79-0.86) in women. Dyslipidemia increased from the 1970s to the 1980s but declined in the succeeding decade. A combination of three or more of these risk factors increased significantly in men by a ratio of 1.15 (95% CI: 1.08-1.22) per decade and in women by 1.20 (95% CI: 1.15-1.27). CONCLUSION: The study shows that individual metabolic risk factors followed divergent trends over the period of three decades even though the combination of three or more risk factors used as a proxy for the metabolic syndrome appeared to be stable over the last two of the decades. The two key components of the syndrome, namely BMI and glucose levels, increased significantly and deserve professional attention.
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10. |
- Borena, Wegene, et al.
(author)
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Metabolic risk factors and primary liver cancer in a prospective study of 578,700 adults
- 2012
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In: International Journal of Cancer. - Malden, MA : Wiley. - 0020-7136 .- 1097-0215. ; 131:1, s. 193-200
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Journal article (peer-reviewed)abstract
- Initial studies have indicated diabetes and obesity to be risk factors for hepatocellular carcinoma; but the association between other metabolic risk factors and primary liver cancer (PLC) has not been investigated. The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria and Sweden with data on 578,700 subjects. We used Cox proportional hazard models to calculate relative risks (RRs) of PLC by body mass index (BMI), blood pressure and plasma levels of glucose, cholesterol and triglycerides as continuous standardized variables (z-score with mean = 0 and standard deviation (SD) = 1) and their standardized sum of metabolic syndrome (MetS) z-score. RRs were corrected for random error in measurements. During an average follow-up of 12.0 years (SD = 7.8), 266 PLCs were diagnosed among cohort members. RR of liver cancer per unit increment of z-score adjusted for age, smoking status and BMI and stratified by birth year, sex and sub-cohorts, was for BMI 1.39 (95% confidence interval (CI) 1.241.58), mid blood pressure 2.08 (0.954.73), blood glucose 2.13 (1.552.94) cholesterol 0.62 (0.510.76) and serum triglycerides 0.85 (0.651.10). The RR per one unit increment of the MetS z-score was 1.35 (1.121.61). BMI, glucose and a composite MetS score were positively and cholesterol negatively associated with risk of liver cancer.
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11. |
- Borena, Wegene, et al.
(author)
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Serum triglycerides and cancer risk in the metabolic syndrome and cancer (Me-Can) collaborative study
- 2011
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In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 22:2, s. 291-299
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Journal article (peer-reviewed)abstract
- To assess the association between serum triglyceride levels and cancer risk. The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden; the current study included data on 257,585 men and 256,512 women. The mean age at study entry was 43.8 years for men and 44.2 years for women. The mean follow-up time was 13.4 years (SD = 8.5) for men and 11.9 years (SD = 7.2) for women. Excluding the first year of follow-up, 23,060 men and 15,686 women were diagnosed with cancer. Cox regression models were used to calculate relative risk (RR) of cancer for triglyceride levels in quintiles and as a continuous variable. RRs were corrected for random error by use of regression dilution ratio. Relative risk for top quintile versus bottom quintile of triglycerides of overall cancer was 1.16 (95% confidence interval 1.06-1.26) in men and 1.15 (1.05-1.27) in women. For specific cancers, significant increases for top quintile versus bottom quintile of triglycerides among men were found for cancers of the colon, respiratory tract, the kidney, melanoma and thyroid and among women, for respiratory, cervical, and non-melanoma skin cancers. Data from our study provided evidence for a possible role of serum triglycerides in cancer development.
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12. |
- Danaei, Goodarz, et al.
(author)
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Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
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In: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
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Journal article (peer-reviewed)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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13. |
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14. |
- Edlinger, Michael, et al.
(author)
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Blood pressure and other metabolic syndrome factors and risk of brain tumour in the large population-based Me-Can cohort study
- 2012
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In: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 30:2, s. 290-296
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Journal article (peer-reviewed)abstract
- OBJECTIVES:: Brain tumour has few established determinants. We assessed to which extent risk of brain tumour was related to metabolic syndrome factors in adults. METHODS:: In the Me-Can project, 580 000 individuals from Sweden, Austria, and Norway were followed for a median of 10 years after baseline measurement. Data on brain tumours were obtained from national cancer registries. The factors of metabolic syndrome (BMI, SBP and DBP, and blood levels of glucose, cholesterol, and triglycerides), separately and combined, were analysed in quintiles and for transformed z-scores (mean transformed to 0 and standard deviation to 1). Cox proportional hazards multivariate regression models were used, with corrections for measurement error. RESULTS:: During follow-up, 1312 primary brain tumours were diagnosed, predominantly meningioma (n = 348) and high-grade glioma (n = 436). For meningioma, the hazard ratio was increased for z-scores of SBP [hazard ratio = 1.27 per unit standard deviation, 95% confidence interval (CI) 1.03-1.57], of DBP (hazard ratio = 1.29, 95% CI 1.04-1.58), and of the combined metabolic syndrome score (hazard ratio = 1.31, 95% CI 1.11-1.54). An increased risk of high-grade glioma was found for DBP (hazard ratio = 1.23, 95% CI 1.01-1.50) and triglycerides (hazard ratio = 1.35, 95% CI 1.05-1.72). For both meningioma and high-grade glioma, the risk was more than double in the fifth quintiles of DBP compared to the lowest quintile. For meningioma this risk was even larger for SBP. CONCLUSION:: Increased blood pressure was associated with risk of brain tumours, especially of meningiomas.
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15. |
- Fritz, Josef, et al.
(author)
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Body mass index, triglyceride-glucose index, and prostate cancer death : a mediation analysis in eight European cohorts
- 2024
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In: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 130, s. 308-316
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Journal article (peer-reviewed)abstract
- Background: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited.Methods: We included 259,884 men from eight European cohorts, with 11,760 incident PCa’s and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index.Results: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01–1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14–1.35, of which 28%; 4%–52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death.Conclusions: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.
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16. |
- Fritz, Josef, et al.
(author)
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Body mass index, triglyceride-glucose index, and prostate cancer death : a mediation analysis in eight European cohorts
- 2024
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In: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 130:2, s. 308-316
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited.METHODS: We included 259,884 men from eight European cohorts, with 11,760 incident PCa's and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index.RESULTS: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01-1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14-1.35, of which 28%; 4%-52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death.CONCLUSIONS: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.
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17. |
- Fritz, Josef, et al.
(author)
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Insulin resistance measured by the triglyceride-glucose index and risk of obesity-related cancers : An epidemiological investigation in more than 500,000 individuals.
- 2019
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 37:15, s. 1552-1552
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Journal article (other academic/artistic)abstract
- Background: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. We aimed to determine to what extent insulin resistance measured as the logarithmized triglyceride glucose product (TyG index) mediates the effect of BMI on risk of obesity-related cancers. Methods: A total of 510,471 individuals from six European cohorts with a mean age of 43.1 years were included in the study. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with ten common obesity-related cancer sites, and quantified the proportion of the effect of BMI mediated through TyG index. Results: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney (hazard ratio (HR) per one standard deviation increase 1.13, 95% confidence interval: 1.07-1.20), liver (1.13, 1.04-1.23), pancreas (1.12, 1.06-1.19), colon (1.07, 1.03-1.10), and rectum (1.09, 1.04-1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%), and colon (20%); smaller proportions for kidney (15%) and liver (11%); none for endometrium, ovary and breast (postmenopausal). Conclusions: In this pooled cohort study including more than 500,000 individuals, insulin resistance measured as the logarithmized triglyceride glucose product significantly mediated the effect of overweight and obesity on risk of cancers of the kidney, liver, pancreas, colon, and rectum. In contrast, insulin resistance did not mediate the risk for cancers of the endometrium, ovary and breast. Our results confirm a promoting role of insulin resistance in the pathogenesis of gastrointestinal cancers. Although often claimed, insulin resistance does not appear to connect excess body weight with cancers of the female reproductive organs.
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18. |
- Fritz, Josef, et al.
(author)
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Metabolic Mediators of the Effects of Family History and Genetic Risk Score on Coronary Heart Disease-Findings from the Malmö Diet and Cancer Study
- 2017
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In: Journal of the American Heart Association. - 2047-9980. ; 6:3
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Journal article (peer-reviewed)abstract
- Background--Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed by a genetic risk score (GRS) are predictors of CHD risk. It is, however, uncertain to what extent these risk predictors are mediated by major metabolic pathways. Methods and Results--Total effects of self-reported family history and a 50-variant GRS (GRS50), as well as effects mediated by apolipoprotein B and A-I (apoB, apoA-I), blood pressure, and diabetes mellitus, on incidence of CHD were estimated in 23 595 participants of the Malmö Diet and Cancer study (a prospective, population-based study). During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. Family history of CHD and GRS50 (highest versus other quintiles) were associated with incident CHD, with hazard ratios of 1.52 (95% CI: 1.39-1.65) and 1.53 (95% CI: 1.39-1.68), respectively, after adjusting for age, sex, and smoking status. Small proportions of the family history effect were mediated by metabolic risk factors: 8.3% (95% CI: 5.8-11.7%) by the apoB pathway, 1.7% (95% CI: 0.2-3.4%) by apoA-I, 8.5% (95% CI: 5.9-12.0%) by blood pressure, and 1.5% (95% CI: 0.8% to 3.8%) by diabetes mellitus. Similarly, small proportions of GRS50 were mediated: 8.1% (95% CI: 5.5-11.8%) by apoB, 1.2% (95% CI: 0.5-3.0%) by apoA-I, 4.2% (95% CI: 1.3-7.5%) by blood pressure, and 0.9% (95% CI: 3.7% to 1.6%) by diabetes mellitus. Conclusions--A fraction of the CHD risk associated with family history or with GRS50 is mediated through elevated blood lipids and hypertension, but not through diabetes mellitus. However, a major part (≥80%) of the genetic effect operates independently of established metabolic risk factor pathways.
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19. |
- Fritz, Josef, et al.
(author)
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The triglyceride-glucose index as a measure of insulin resistance and risk of obesity-related cancers
- 2020
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 49:1, s. 193-204
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Journal article (peer-reviewed)abstract
- BACKGROUND: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified.METHODS: Altogether 510 471 individuals from six European cohorts, with a mean age of 43.1 years, were included. We used the triglyceride glucose product (TyG index) as a surrogate measure for insulin resistance. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with 10 common obesity-related cancers, and quantified the proportion of the effect of BMI mediated through TyG index on the log-transformed hazard ratio (HR) scale.RESULTS: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney HR per one standard deviation increase 1.13, 95% confidence interval: 1.07 to 1.20], liver (1.13, 1.04 to 1.23), pancreas (1.12, 1.06 to 1.19), colon (1.07, 1.03 to 1.10) and rectum (1.09, 1.04 to 1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%) and colon (20%); smaller proportions for kidney (15%) and liver (11%). Little or no mediation was observed for breast (postmenopausal), endometrial and ovarian cancer. Results were similar for males and females, except for pancreatic cancer where the proportions mediated were 20% and 91%, respectively.CONCLUSIONS: The TyG index was associated with increased risk of cancers of the digestive system and substantially mediated the effect of BMI, suggesting that insulin resistance plays a promoting role in the pathogenesis of gastrointestinal cancers.
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20. |
- Häggstrom, Christel, et al.
(author)
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Prospective Study on Metabolic Factors and Risk of Prostate Cancer
- 2012
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In: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 118:24, s. 6199-6206
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Journal article (peer-reviewed)abstract
- BACKGROUND: There are inconsistent data regarding the association between metabolic factors, separately and combined, and the risk of prostate cancer and death from prostate cancer. METHODS: In the Metabolic Syndrome and Cancer Project (Me-Can), data on body mass index (BMI); blood pressure; and blood levels of glucose, cholesterol, and triglycerides were collected for 289,866 men. Cox proportional hazard models were used to calculate relative risks (RRs) by exposures in quintiles as well as for z scores (with a mean of 0 and a standard deviation of 1) together with a composite sum of scores to assess the combined effect of metabolic factors. RRs were corrected for random errors in measurement. RESULTS: During a mean follow-up of 12 years, 6673 men were diagnosed with prostate cancer and 961 died of the disease. Men with high levels of glucose and triglycerides were found to have a decreased risk of prostate cancer: top versus bottom quintile of glucose: RR, 0.82 (95% confidence interval [95% CI], 0.62-1.08; P value for trend = .03) and top versus bottom quintile of triglycerides: RR, 0.88 (95% CI, 0.74-1.04; P value for trend = .001). High BMI, elevated blood pressure, and a high composite z score were found to be associated with an increased risk of death from prostate cancer: top versus bottom quintile of BMI: RR, 1.36 (95% CI, 1.08-1.71); systolic blood pressure: RR, 1.62 (95% CI, 1.07-2.45); and per 1-unit increase of the composite z score: RR, 1.13 (95% CI, 1.03-1.25). CONCLUSIONS: The authors found no evidence of an association between high levels of metabolic factors and the risk of prostate cancer, but high BMI, elevated blood pressure, and a composite score of all metabolic factors were associated with an increased risk of death from prostate cancer. Cancer 2012;118:6199-206. (C) 2012 American Cancer Society.
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21. |
- Häggström, Christel, et al.
(author)
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Competing risk analysis of metabolic factors and prostate cancer
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Other publication (other academic/artistic)abstract
- Background: Men at risk of prostate cancer are also at risk of competing events but this has been ignored in most studies of metabolic aberrations and prostate cancer. The aim of this study was to assess probabilities of prostate cancer and prostate cancer death by use of competing risk analysis.Methods: In the Metabolic syndrome and Cancer project (Me-Can), data on body mass index, blood pressure, glucose, total cholesterol, and triglycerides were collected from 285 040 men. Probabilities of prostate cancer, prostate cancer death and competing events, i.e. all-cause death or death from other causes, respectively, were calculated for men with normal (bottom 84%) and high (top 16%) levels of each metabolic factor and a composite score based on all metabolic factorsResults: During follow up, 5893 men were diagnosed with prostate cancer, 1013 men died of prostate cancer, and 26 328 men died of other causes. Men with high levels of metabolic factors had decreased probability of prostate cancer, similar probability of prostate cancer death, and increased probability of other causes of death compared to men with normal levels. After 1996, when prostate specific antigen was used for detection of prostate cancer, men up to 80 years with normal levels of metabolic factors had 13% probability of prostate cancer and 37% probability of death from all causes. For men with high levels of metabolic factors, corresponding probabilities were 12% and 47%.Conclusions: Men with metabolic aberrations had a decreased probability of prostate cancer but a substantially higher probability of death from all causes.
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22. |
- Häggström, Christel, et al.
(author)
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Linear age-course effects on the associations between body mass index, triglycerides, and female breast and male liver cancer risk : An internal replication study of 800,000 individuals
- 2020
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:1, s. 58-67
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Journal article (peer-reviewed)abstract
- Apart from the consistently observed differential association between obesity and breast cancer risk by menopausal status, the associations between obesity and other metabolic imbalances with risks of cancers have not been systematically investigated across the age-course. We created two random 50–50% cohorts from six European cohorts comprising 813,927 individuals. In the “discovery cohort”, we used Cox regression with attained age as time-scale and tested interactions between body mass index (BMI), blood pressure, plasma glucose, triglycerides and cholesterol, and attained age in relation to cancer risk. Results with a p-value below 0.05 were additionally tested in the “replication cohort” where a replicated result was considered evidence of a linear interaction with attained age. These findings were investigated by flexible parametric survival models for any age-plateaus in their shape of associations with cancer risk across age. Consistent with other studies, BMI was negatively related to breast cancer risk (n cases = 11,723) among younger (premenopausal) women. However, the association remained negative for several years after menopause and, although gradually weakening over age, the association became positive only at 62 years of age. This linear and positive age-interaction was also found for triglycerides and breast cancer, and for BMI and triglycerides in relation to liver cancer among men (n cases = 444). These findings are unlikely to be due to chance owing to the replication. The linear age-interactions in breast cancer may suggest an influence by other age-related factors than menopause; however, further investigation of age-related effect modifiers in both breast and liver cancer is needed.
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23. |
- Häggström, Christel, et al.
(author)
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Metabolic factors associated with risk of renal cell carcinoma
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2, s. e57475-
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Journal article (peer-reviewed)abstract
- Previous studies have shown that obesity and hypertension are associated with increased risk of renal cell carcinoma (RCC), but less is known about the association to other metabolic factors. In the Metabolic Syndrome and Cancer project (Me-Can) data on body mass index (BMI, kg/m2), blood pressure, and circulating levels of glucose, cholesterol, and triglycerides were collected from 560,388 men and women in cohorts from Norway, Austria, and Sweden. By use of Cox proportional hazard models, hazard ratios (HR) were calculated for separate and composite metabolic exposures. During a median follow-up of 10 years, 592 men and 263 women were diagnosed with RCC. Among men, we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 1.51, 95% CI 1.13-2.03), systolic blood pressure, (HR = 3.40, 95% CI 1.91-6.06), diastolic blood pressure, (HR = 3.33, 95% CI 1.85-5.99), glucose, (HR = 3.75, 95% CI 1.46-9.68), triglycerides, (HR = 1.79, 95% CI 1.00-3.21) and a composite score of these metabolic factors, (HR = 2.68, 95% CI 1.75-4.11). Among women we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 2.21, 95% CI 1.32-3.70) and the composite score, (HR = 2.29, 95% CI 1.12-4.68). High levels of the composite score were also associated with risk of death from RCC among both men and women. No multiplicative statistical or biological interactions between metabolic factors on risk of RCC were found. High levels of BMI, blood pressure, glucose and triglycerides among men and high BMI among women were associated with increased risk of RCC.
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24. |
- Häggström, Christel, et al.
(author)
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Metabolic syndrome and risk of bladder cancer: prospective cohort study in the metabolic syndrome and cancer project (Me-Can)
- 2011
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 128:8, s. 1890-1898
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Journal article (peer-reviewed)abstract
- There are little data on the putative association between factors in the metabolic syndrome (MetS) and risk of bladder cancer. In the Metabolic Syndrome and Cancer project (Me-Can), measurements of height, weight, blood pressure and circulating levels of glucose, cholesterol, and triglycerides had been collected from 578,700 subjects in cohorts in Norway, Austria, and Sweden. We used Cox proportional hazard models to calculate relative risks (RRs) of bladder cancer by exposures divided into quintiles, in categories according to the World Health Organisation (WHO) and as a continuous standardized variable (z-score with mean = 0 and standard deviation = 1) for each separate component and its standardized sum, a composite MetS score. RRs were corrected for random error in measurements. During a mean follow-up of 11.7 years (SD = 7.6), 1,587 men and 327 women were diagnosed with bladder cancer. Significant associations with risk were found among men per one unit increment of z-score for blood pressure, RR 5 1.13 (95% CI 1.03-1.25), and the composite MetS score, RR = 1.10 (95% CI 1.01-1.18). Among women, glucose was nonsignificantly associated with risk, RR = 1.41 (95% CI 0.97-2.06). No statistically significant interactions were found between the components in the MetS in relation to bladder cancer risk. Hypertension and a composite MetS score were significantly but modestly associated with an increased risk of bladder cancer among men and elevated glucose was associated with a nonsignificant increase in risk among women. Epidemiology
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25. |
- Häggström, Christel, et al.
(author)
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Prostate Cancer, Prostate Cancer Death, and Death from Other Causes, Among Men with Metabolic Aberrations
- 2014
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In: Epidemiology. - 1044-3983 .- 1531-5487. ; 25:6, s. 823-828
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Journal article (peer-reviewed)abstract
- Background: Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes.Methods: In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score.Results: During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%.Conclusions: In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.
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