| 181. |
- Jochems, Sylvia H.J., et al.
(författare)
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Prediagnostic markers of insulin resistance and prostate cancer risk and death : A pooled study
- 2023
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:12, s. 13732-13744
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundInsulin resistance has been shown to be related to a higher risk of several cancers, but the association with prostate cancer (PCa) has been inconsistent.MethodsWe investigated prediagnostic markers of insulin resistance in men in four cohorts in Sweden, in relation to PCa risk (total, non-aggressive and aggressive) and PCa death using multivariable-adjusted Cox regression. The number of men, PCa cases and PCa deaths was up to 66,668, 3940 and 473 for plasma glucose and the triglyceride-glucose (TyG) index, and up to 3898, 586 and 102 for plasma insulin, glycated haemoglobin (HbA1c) and leptin.ResultsHigher HbA1c was related to a lower risk of non-aggressive PCa but no significant associations were found for insulin resistance markers with the risk of aggressive or total PCa. In PCa cases, higher glucose and TyG index were related to a higher risk of PCa death (hazard ratio [HR] per higher standard deviation, 1.22, 95% CI 1.00–1.49 and 1.24, 95% CI 1.00–1.55), which further increased when restricting the analyses to glucose and TyG index measures taken <10 years before the PCa diagnosis (HR, 1.70, 95% CI 1.09–2.70 and 1.66, 95% CI 1.12–2.51). No associations were observed for other markers in relation to PCa death.ConclusionsThe results of this study showed no associations of insulin resistance markers with the risk of clinically relevant PCa, but higher glucose and TyG index were associated with poorer survival from PCa. The lack of association for other insulin resistance markers may be due to their smaller sample size.
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| 182. |
- Jochems, Sylvia H J, et al.
(författare)
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Smoking and risk of prostate cancer and prostate cancer death : a pooled study
- 2023
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 83:5, s. 422-431
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prospective and detailed investigations of smoking and prostate cancer (PCa) risk and death are lacking.Objective: To investigate prediagnosis smoking habit (status, intensity, duration, and cessation) as a risk factor, on its own and combined with body mass index (BMI), for PCa incidence and death.Design, setting, and participants: We included 351 448 men with smoking information from five Swedish cohorts. Outcome measurements and statistical analysis: We used Cox regression to calculate hazard ratios (HRs) and confidence intervals (CIs) for PCa incidence (n = 24 731) and death (n = 4322).Results and limitations: Smoking was associated with a lower risk of any PCa (HR 0.89, 95% CI 0.86–0.92), which was most pronounced for low-risk PCa (HR 0.74, 95% CI 0.69–0.79) and was restricted to PCa cases diagnosed in the prostate-specific antigen (PSA) era. Smoking was associated with a higher risk of PCa death in the full cohort (HR 1.10, 95% CI 1.02–1.18) and in case-only analysis adjusted for clinical characteristics (HR 1.20, 95% CI 1.11–1.31), which was a consistent finding across case groups (p = 0.8 for heterogeneity). Associations by smoking intensity and, to lesser degree, smoking duration and cessation, supported the associations for smoking status. Smoking in combination with obesity (BMI ≥30 kg/m2) further decreased the risk of low-risk PCa incidence (HR 0.40, 95% CI 0.30–0.53 compared to never smokers with BMI <25 kg/m2) and further increased the risk of PCa death (HR 1.49, 95% CI 1.21–1.84). A limitation of the study is that only a subgroup of men had information on smoking habit around the time of their PCa diagnosis.Conclusions: The lower PCa risk for smokers in the PSA era, particularly for low-risk PCa, can probably be attributed to low uptake of PSA testing by smokers. Poor survival for smokers, particularly obese smokers, requires further study to clarify the underlying causes and the preventive potential of smoking intervention for PCa death.Patient summary: Smokers have a higher risk of dying from prostate cancer, which further increases with obesity.
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| 183. |
- Jochems, Sylvia, et al.
(författare)
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Waist circumference and a body shape index and prostate cancer risk and mortality
- 2021
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Ingår i: Cancer Medicine. - : Blackwell Publishing. - 2045-7634. ; 10:8, s. 2885-2896
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Tidskriftsartikel (refereegranskat)abstract
- We recently found a negative association between body mass index (BMI) and the risk of localised prostate cancer (PCa), no association with advanced PCa, and a positive association with PCa‐specific mortality. In a 15% subpopulation of that study, we here investigated the measures of abdominal adiposity including waist circumference (WC) and A Body Shape Index (ABSI) in relation to PCa risk and mortality. We used data from 58,457 men from four Swedish cohorts to assess WC and ABSI in relation to PCa risk according to cancer risk category, including localised asymptomatic and symptomatic PCa and advanced PCa, and PCa‐specific mortality. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During, on average, 10 years of follow‐up, 3290 men were diagnosed with PCa and 387 died of PCa. WC was negatively associated with the risk of total PCa (HR per 10 cm, 0.95; 95% CI 0.92–0.99), localised PCa (HR per 10 cm, 0.93, 95% CI 0.88–0.96) and localised asymptomatic PCa cases detected through a prostate‐specific antigen (PSA) test (HR per 10 cm, 0.87, 95% CI 0.81–0.94). WC was not associated with the risk of advanced PCa (HR per 10 cm, 1.02, 95% CI 0.93–1.14) or with PCa‐specific mortality (HR per 10 cm, 1.04, 95% CI 0.92–1.19). ABSI showed no associations with the risk of PCa or PCa‐specific mortality. While the negative association between WC and the risk of localised PCa was partially driven by PSA‐detected PCa cases, no association was found between abdominal adiposity and clinically manifest PCa in our population.
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| 184. |
- Klein, Robert J., et al.
(författare)
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Prostate cancer polygenic risk score and prediction of lethal prostate cancer
- 2022
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Ingår i: npj Precision Oncology. - : Nature Publishing Group. - 2397-768X. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for prostate cancer incidence have been proposed to optimize prostate cancer screening. Prediction of lethal prostate cancer is key to any stratified screening program to avoid excessive overdiagnosis. Herein, PRS for incident prostate cancer was evaluated in two population-based cohorts of unscreened middle-aged men linked to cancer and death registries: the Västerbotten Intervention Project (VIP) and the Malmö Diet and Cancer study (MDC). SNP genotypes were measured by genome-wide SNP genotyping by array followed by imputation or genotyping of selected SNPs using mass spectrometry. The ability of PRS to predict lethal prostate cancer was compared to PSA and a commercialized pre-specified model based on four kallikrein markers. The PRS was associated with incident prostate cancer, replicating previously reported relative risks, and was also associated with prostate cancer death. However, unlike PSA, the PRS did not show stronger association with lethal disease: the hazard ratio for prostate cancer incidence vs. prostate cancer metastasis and death was 1.69 vs. 1.65 in VIP and 1.25 vs. 1.25 in MDC. PSA was a much stronger predictor of prostate cancer metastasis or death with an area-under-the-curve of 0.78 versus 0.63 for the PRS. Importantly, addition of PRS to PSA did not contribute additional risk stratification for lethal prostate cancer. We have shown that a PRS that predicts prostate cancer incidence does not have utility above and beyond that of PSA measured at baseline when applied to the clinically relevant endpoint of prostate cancer death. These findings have implications for public health policies for delivery of prostate cancer screening. Focusing polygenic risk scores on clinically significant endpoints such as prostate cancer metastasis or death would likely improve clinical utility.
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| 185. |
- Loeb, Stacy, et al.
(författare)
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Five-year Nationwide Follow-up Study of Active Surveillance for Prostate Cancer
- 2015
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 67:2, s. 233-238
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Tidskriftsartikel (refereegranskat)abstract
- Background: Active surveillance (AS) is an important yet underutilized strategy to reduce prostate cancer (PCa) overtreatment. Objective: To examine the 5-yr outcomes of AS in a population-based setting. Design, setting, and participants: From the National Prostate Cancer Register of Sweden, we identified 11 726 men <= 70 yr diagnosed with very low-risk to intermediate-risk PCa from 2003 to 2007 who completed 5 yr of follow-up. Of these men, 1729 (15%) chose AS for the primary management strategy. Outcome measurements and statistical analysis: We calculated the probability of discontinuation of AS over time, and Cox proportional hazards models were used to determine factors associated with discontinuation. Reasons for discontinuation were assessed by data extraction from medical charts. Results and limitations: By 5 yr, 64% of the men remained on AS. Predictors of discontinuation were younger age, fewer comorbidities, more education, higher prostate-specific antigen (PSA), and clinical stage T2 disease; marital status did not predict discontinuation. In a subset with data on the reason for discontinuation (86%), 20% of men discontinued because of patient preference, 52% because of PSA progression, 24% because of biopsy progression, and 3% for other reasons. Conclusions: In a population-based setting, the majority of men remained on AS at 5 yr. However, one-fifth of the men who discontinued AS did so for nonbiologic reasons. Thus, there is a need for support and counseling for men to continue AS in the absence of signs of progression to improve adherence to AS and decrease overtreatment. Patient summary: Active surveillance (AS) is an important option to delay or avoid treatment for men with favorable prostate cancer features. This study shows that at 5 yr, 64% of men across an entire population remained on AS. We concluded that AS is a durable option and that counseling may be useful to promote adherence for men without progression.
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| 186. |
- Loeb, Stacy, et al.
(författare)
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Uptake of active surveillance for very-low-risk prostate cancer in Sweden
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:10, s. 1393-1398
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Active surveillance is an important option to reduce prostate cancer overtreatment, but it remains underutilized in many countries. Models from the United States show that greater use of active surveillance is important for prostate cancer screening to be cost-effective.oObjectives: To perform an up-to-date, nationwide, population-based study on use of active surveillance for localized prostate cancer in Sweden.Design, setting, and participants: Cross-sectional study in the National Prostate Cancer Register (NPCR) of Sweden from 2009 through 2014. The NPCR has data on 98% of prostate cancers diagnosed in Sweden and has comprehensive linkages to other nationwide databases. Overall, 32 518 men with a median age of 67 years were diagnosed with favorable-risk prostate cancer, including 4693, 15 403, and 17 115 men with very-low-risk (subset of the low-risk group) (clinical stage, T1c; Gleason score, ≤6; prostate-specific antigen [PSA], <10 ng/mL; PSA density <0.15 ng/mL/cm3; and <8-mm total cancer length in ≤4 positive biopsy cores), low-risk (including all men in the very-low-risk group) (T1-T2; Gleason score, ≤6; and PSA, <10 ng/mL), and intermediate-risk disease (T1-T2 with Gleason score, 7 and/or PSA, 10-20 ng/mL).Exposures: Diagnosis with favorable-risk prostate cancer.Main outcomes and measures: Utilization of active surveillance.Results: The use of active surveillance increased in men of all ages from 57% (380 of 665) to 91% (939 of 1027) for very-low-risk prostate cancer and from 40% (1159 of 2895) to 74% (1951 of 2644) for low-risk prostate cancer, with the strongest increase occurring from 2011 onward. Among men aged 50 to 59 years, 88% (211 of 240) with very-low-risk and 68% (351 of 518) with low-risk disease chose active surveillance in 2014. Use of active surveillance for intermediate-risk disease remained lower, 19% (561 of 3030) in 2014.Conclusions and relevance: Active surveillance has become the dominant management for low-risk prostate cancer among men in Sweden, with the highest rates yet reported and almost complete uptake for very-low-risk cancer. These data should serve as a benchmark to compare the use of active surveillance for favorable-risk disease around the world.
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| 187. |
- Nagel, Gabriele, et al.
(författare)
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Metabolic factors and the risk of small intestine cancers : pooled study of 800 000 individuals in the Metabolic syndrome and Cancer project
- 2021
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 149:1, s. 66-74
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Tidskriftsartikel (refereegranskat)abstract
- To explore the largely unknown etiology of small intestine cancer, we examined metabolic factors and risk of small intestine cancer overall and by subtypes. Amongst 404 220 women and 403 265 men in six European cohorts, we applied Cox regression with adjustment for smoking and body mass index (BMI), to calculate sex-specific hazard ratios (HR) of small intestine cancer by levels of BMI, mean arterial pressure (MAP), and plasma total cholesterol, triglycerides and glucose. We also calculated HRs for these factors combined (metabolic score; MetS) and used Wald test statistics to investigate pairwise interactions between metabolic factors on risk. We also performed analyses separately per subtype (neuroendocrine tumors (NETs) and adenocarcinomas). During a median follow-up of 16.9 years, 144 women and 195 men were diagnosed with small intestine cancer, including 184 NETs and 99 adenocarcinomas. Among men, no main associations or interactions between metabolic factors were observed in relation to the risk of small intestine cancer. Among women, triglycerides were positively and linearly associated with risk (HR per standard deviation [SD]: 1.23, 95% CI 1.04 to 1.46), and a positive association was also observed for the MetS (HR per SD: 1.25, 95% CI 1.02 to 1.52). Positive interactions were observed among women between triglycerides and cholesterol (p=0.0005), and between MAP and glucose (p=0.009), on risk. Glucose was positively associated with adenocarcinomas among women. This large, prospective study suggests that elevated triglycerides, and metabolic factors in interaction, confer an increased risk of small intestine cancer among women, but not among men.
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| 188. |
- Papadimitriou, Nikos, et al.
(författare)
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A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study
- 2020
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Ingår i: European Journal of Nutrition. - : Springer Nature. - 1436-6207 .- 1436-6215. ; 59:7, s. 2929-2937
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive.Methods: A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate (FDR < 5%) method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS).Results: A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC (minimum FDR-corrected P, 0.37). Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS.Conclusions: Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature.
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| 189. |
- Perez-Cornago, Aurora, et al.
(författare)
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Fruit and vegetable intake and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 141:2, s. 287-297
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Tidskriftsartikel (refereegranskat)abstract
- Several dietary factors have been studied in relation to prostate cancer; however, most studies have not reported on subtypes of fruit and vegetables or tumor characteristics, and results obtained so far are inconclusive. This study aimed to examine the prospective association of total and subtypes of fruit and vegetable intake with the incidence of prostate cancer overall, by grade and stage of disease, and prostate cancer death. Lifestyle information for 142,239 men participating in the European Prospective Investigation into Cancer and Nutrition from 8 European countries was collected at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow-up time of 13.9 years, 7,036 prostate cancer cases were identified. Compared with the lowest fifth, those in the highest fifth of total fruit intake had a significantly reduced prostate cancer risk (HR = 0.91; 95% CI = 0.83-0.99; p-trend = 0.01). No associations between fruit subtypes and prostate cancer risk were observed, except for citrus fruits, where a significant trend was found (HR = 0.94; 95% CI = 0.86-1.02; p-trend = 0.01). No associations between total and subtypes of vegetables and prostate cancer risk were observed. We found no evidence of heterogeneity in these associations by tumor grade and stage, with the exception of significant heterogeneity by tumor grade (pheterogeneity<0.001) for leafy vegetables. No significant associations with prostate cancer death were observed. The main finding of this prospective study was that a higher fruit intake was associated with a small reduction in prostate cancer risk. Whether this association is causal remains unclear. What's new? The role of diet in prostate-cancer etiology is uncertain, and associations may vary by tumor characteristics. In this prospective, longitudinal study, the authors examined the association of total and subtypes of fruit and vegetable intake with the overall incidence of prostate cancer. They then analyzed incidence by grade, stage of disease, and prostate-cancer death. They found that higher fruit intake was associated with a small reduction in prostate cancer risk, and that this association did not differ by tumor characteristics.
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| 190. |
- Stattin, Pär, et al.
(författare)
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Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers : a Nested Case-Control Study
- 2015
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 68:2, s. 207-213
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Tidskriftsartikel (refereegranskat)abstract
- Background: A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death. Objective: To increase the specificity of screening for lethal PCa at an early stage. Design, setting, and participants: We conducted a case-control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Vasterbotten, Sweden. Of 40 379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12 542 men were followed for > 15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis. Outcome measurements and statistical analysis: Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers. Results and limitations: Mostmetastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (<= 0.6%). Among men with PSA > 2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA > 2 ng/ml were defined as low risk by this model and had a <= 1% 15-yr risk of metastasis. Conclusions: Screening at ages 50-60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making. Patient summary: For men in their fifties, screening should focus on those in the top 10% to 25% of PSA values because the majority of subsequent cases of distant metastasis are found among these men. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making.
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