| 1. |
- Häggström, Christel, et al.
(author)
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Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer
- 2017
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In: Int J Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:3, s. 611-617
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Journal article (peer-reviewed)abstract
- Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti-diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD = 9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD = 3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR = 0.85, 95% CI = 0.82-0.88) but among men with T2DM, those on metformin had no decrease (HR = 0.96, 95% CI = 0.77-1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR = 0.73, 95% CI = 0.55-0.98), compared to men with T2DM not on anti-diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR = 1.11, 95% CI = 0.95-1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.
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| 2. |
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| 3. |
- Arthur, Rhonda, et al.
(author)
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Serum glucose, triglycerides, and cholesterol in relation to prostate cancer death in the Swedish AMORIS study
- 2019
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In: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 30:2, s. 195-206
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Journal article (peer-reviewed)abstract
- Purpose: Lifestyle-related conditions such as obesity are associated with prostate cancer progression, but the associations with hyperglycemia and dyslipidemia are unclear. This study, therefore, aims to examine the association of glucose, triglycerides, and total cholesterol with prostate cancer death. Methods: From the Swedish AMORIS cohort, we selected 14,150 men diagnosed with prostate cancer between 1996 and 2011 who had prediagnostic measurements of serum glucose, triglycerides, and total cholesterol. Multivariable Cox proportional hazards regressionmodels were used to determine the hazard ratios for death in relation to the aforementioned metabolic markers. Results: Using clinical cut-off points, a non-significant positive association was observed between glucose and prostate cancer death. When compared to those with glucose in the lowest quartile, those in the highest quartile had greater risk of prostate cancer death (HR 1.19; 95% CI 1.02-1.39). However, neither total cholesterol nor triglycerides were associated with prostate cancer death. Glucose and triglycerides were positively associated with overall, cardiovascular, and other deaths. Hypercholesterolemia was only associated with risk of CVD death. Conclusion: Our results suggest that glucose levels may influence prostate cancer survival, but further studies using repeated measurements are needed to further elucidate how glucose levels may influence prostate cancer progression.
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| 4. |
- Beckmann, Kerri, et al.
(author)
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Chronic inflammatory diseases, anti-inflammatory medications and risk of prostate cancer : a population-based case-control study
- 2019
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In: BMC Cancer. - : BioMed Central. - 1471-2407 .- 1471-2407. ; 19
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Journal article (peer-reviewed)abstract
- Background: Whether chronic inflammation increases prostate cancer risk remains unclear. This study investigated whether chronic inflammatory diseases (CID) or anti-inflammatory medication use (AIM) were associated with prostate cancer risk.Methods: Fifty-five thousand nine hundred thirty-seven cases (all prostate cancer, 2007–2012) and 279,618 age-matched controls were selected from the Prostate Cancer Database Sweden. CIDs and AIMs was determined from national patient and drug registers. Associations were investigated using conditional logistic regression, including for disease/drug subtypes and exposure length/dose.Results: Men with a history of any CID had slightly increased risk of any prostate cancer diagnosis (OR: 1.08; 95%CI: 1.04–1.12) but not ‘unfavourable’ (high-risk or advanced) prostate cancer. Generally, risk of prostate cancer was highest for shorter exposure times. However, a positive association was observed for asthma > 5 years before prostate cancer diagnosis (OR: 1.21; 95%CI: 1.05–1.40). Risk of prostate cancer was increased with prior use of any AIMs (OR: 1.26; 95%CI: 1.24–1.29). A positive trend with increasing cumulative dose was only observed for inhaled glucocorticoids (p < 0.011).Conclusion: Detection bias most likely explains the elevated risk of prostate cancer with prior history of CIDs or use of AIMs, given the higher risk immediately after first CID event and lack of dose response. However, findings for length of time with asthma and dose of inhaled glucocorticoids suggest that asthma may increase risk of prostate cancer through other pathways.
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| 5. |
- Crawley, Danielle, et al.
(author)
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Association between duration and type of androgen deprivation therapy and risk of diabetes in men with prostate cancer
- 2016
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 139:12, s. 2698-2704
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Journal article (peer-reviewed)abstract
- Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti-androgens (AA), orchiectomy, or gonadotropin-releasing hormone (GnRH) agonists compared to an age-matched, PCa-free comparison cohort (n=167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 121.5 years HR: 1.61 (95% CI: 1.36-1.91)], compared to PCa-free men. The risk decreased thereafter (e.g., 324 years HR: 1.17 (95% CI: 0.98-1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95% CI: 0.65-0.84). The incidence of T2DM per 1,000 person-years was 10 for PCa-free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.
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| 6. |
- Häggström, Christel, et al.
(author)
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Heterogeneity in risk of prostate cancer : a Swedish population-based cohort study of competing risks and Type 2 diabetes mellitus
- 2018
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 143:8, s. 1868-1875
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Journal article (peer-reviewed)abstract
- Most previous studies of prostate cancer have not taken into account that men in the studied populations are also at risk of competing event, and that these men may have different susceptibility to prostate cancer risk. The aim of our study was to investigate heterogeneity in risk of prostate cancer, using a recently developed latent class regression method for competing risks. We further aimed to elucidate the association between Type 2 diabetes mellitus (T2DM) and prostate cancer risk, and to compare the results with conventional methods for survival analysis. We analysed the risk of prostate cancer in 126,482 men from the comparison cohort of the Prostate Cancer Data base Sweden (PCBaSe) 3.0. During a mean follow-up of 6years 6,036 men were diagnosed with prostate cancer and 22,393 men died. We detected heterogeneity in risk of prostate cancer with two distinct latent classes in the study population. The smaller class included 9% of the study population in which men had a higher risk of prostate cancer and the risk was stronger associated with class membership than any of the covariates included in the study. Moreover, we found no association between T2DM and risk of prostate cancer after removal of the effect of informative censoring due to competing risks. The recently developed latent class for competing risks method could be used to provide new insights in precision medicine with the target to classify individuals regarding different susceptibility to a particular disease, reaction to a risk factor or response to treatment.
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| 7. |
- Tomic, Katarina, et al.
(author)
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Socioeconomic status and diagnosis, treatment, and mortality in men with prostate cancer. Nationwide population-based study
- 2018
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:12, s. 2478-2484
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Journal article (peer-reviewed)abstract
- Patients with high socioeconomic status (SES) have better cancer outcomes than patients with low SES. This has also been shown in Sweden, a country with tax-financed health care aiming to provide care on equal terms to all residents. The association between income and educational level and diagnostics and treatment as outlined in national guidelines and prostate cancer (Pca) and all-cause mortality was assessed in 74,643 men by use of data in the National Prostate Cancer Register of Sweden and a number of other health care registers and demographic databases. In multivariable logistic regression analysis, men with high income had higher probability of Pca detected in a health-check-up, top versus bottom income quartile, odds ratio (OR) 1.60 (95% CI 1.45-1.77) and lower probability of waiting more than 3 months for prostatectomy, OR 0.77 (0.69-0.86). Men with the highest incomes also had higher probability of curative treatment for intermediate and high-risk cancer, OR 1.77 (1.61-1.95) and lower risk of positive margins, (incomplete resection) at prostatectomy, OR 0.80 (0.71-0.90). Similar, but weaker associations were observed for educational level. At 6 years of follow-up, Pca mortality was modestly lower for men with high income, which was statistically significant for localized high-risk and metastatic Pca in men with no comorbidities. All-cause mortality was less than half in top versus bottom quartile of income (12% vs. 30%, p < 0.001) among men above age 65. Our findings underscore the importance of adherence to guidelines to ensure optimal and equal care for all patients diagnosed with cancer.
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| 8. |
- Teleka, Stanley, et al.
(author)
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Risk of bladder cancer by disease severity in relation to metabolic factors and smoking : A prospective pooled cohort study of 800,000 men and women
- 2018
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 143:12, s. 3071-3082
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Journal article (peer-reviewed)abstract
- Previous studies on metabolic factors and bladder cancer (BC) risk have shown inconsistent results and have commonly not investigated associations separately by sex, smoking, and tumor invasiveness. Among 811,633 participants in six European cohorts, we investigated sex-specific associations between body mass index (BMI), mid-blood pressure (BP, [systolic + diastolic]/2), plasma glucose, triglycerides, total cholesterol and risk of BC overall, non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). Among men, we additionally assessed additive interactions between metabolic factors and smoking on BC risk. During follow-up, 2,983 men and 754 women were diagnosed with BC. Among men, triglycerides and BP were positively associated with BC risk overall (hazard ratio [HR] per standard deviation [SD]: 1.17 [95% confidence interval (CI) 1.06–1.27] and 1.09 [1.02–1.17], respectively), and among women, BMI was inversely associated with risk (HR: 0.90 [0.82–0.99]). The associations for BMI and BP differed between men and women (pinteraction ≤ 0.005). Among men, BMI, cholesterol and triglycerides were positively associated with risk for NMIBC (HRs: 1.09 [95% CI 1.01–1.18], 1.14 [1.02–1.25], and 1.30 [1.12–1.48] respectively), and BP was positively associated with MIBC (HR: 1.23 [1.02–1.49]). Among women, glucose was positively associated with MIBC (HR: 1.99 [1.04–3.81]). Apart from cholesterol, HRs for metabolic factors did not significantly differ between MIBC and NMIBC, and there were no interactions between smoking and metabolic factors on BC. Our study supports an involvement of metabolic aberrations in BC risk. Whilst some associations were significant only in certain sub-groups, there were generally no significant differences in associations by smoking or tumor invasiveness.
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| 9. |
- Lindkvist, Björn, et al.
(author)
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Metabolic risk factors for esophageal squamous cell carcinoma and adenocarcinoma: a prospective study of 580 000 subjects within the Me-Can project
- 2014
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In: BMC Cancer. - London : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Journal article (peer-reviewed)abstract
- Background: Obesity is associated with an increased risk of esophageal adenocarcinoma (EAC) and a decreased risk of esophageal squamous cell carcinoma (ESCC). However, little is known about the risk of EAC and ESCC related to other metabolic risk factors. We aimed to examine the risk of EAC and ESCC in relation to metabolic risk factors, separately and combined in a prospective cohort study. Methods: The Metabolic Syndrome and Cancer cohort includes prospective cohorts in Austria, Norway and Sweden, with blood pressure, lipids, glucose and BMI available from 578 700 individuals. Relative risk (RR) for EAC and ESCC was calculated using Cox's proportional hazards analysis for metabolic risk factors categorized into quintiles and transformed into z-scores. The standardized sum of all z-scores was used as a composite score for the metabolic syndrome (MetS). Results: In total, 324 histologically verified cases of esophageal cancer were identified (114 EAC, 184 ESCC and 26 with other histology). BMI was associated with an increased risk of EAC (RR 7.34 (95% confidence interval, 2.88-18.7) top versus bottom quintile) and negatively associated with the risk of ESCC (RR 0.38 (0.23-0.62)). The mean value of systolic and diastolic blood pressure (mid blood pressure) was associated with the risk of ESCC (RR 1.77 (1.37-2.29)). The composite MetS score was associated with the risk of EAC (RR 1.56 (1.19-2.05) per one unit increase of z-score) but not ESCC. Conclusions: In accordance with previous studies, high BMI was associated with an increased risk of EAC and a decreased risk of ESCC. An association between high blood pressure and risk of ESCC was observed but alcohol consumption is a potential confounding factor that we were not able to adjust for in the analysis. The MetS was associated with EAC but not ESCC. However this association was largely driven by the strong association between BMI and EAC. We hypothesize that this association is more likely to be explained by factors directly related to obesity than the metabolic state of the MetS, considering that no other metabolic factor than BMI was associated with EAC.
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| 10. |
- 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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