The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study.

Purpose: To validate a new 5-tier prognostic classification system to better discriminate cancer specific mortality in men diagnosed with primary non-metastatic prostate cancer. Patients and Methods: We applied a recently described 5 strata model (Cambridge Prognostic Groups-CPG) in 2 international cohorts and tested prognostic performance against the current standard 3 strata classification of low, intermediate or high-risk disease. Diagnostic clinico-pathological data of men from Prostate Cancer Data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality. Results: The PCBaSe cohort included 72,337 men, of whom 7,162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk-regression confirming significant intergroup distinction (p<0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current 3-tier system (C-Index 0.81 vs. 0.77, p<0.0001). This superiority was maintained for every age group division (p<0.0001). Also in the ethnically different Singapore cohort of 2,550 men with 142 prostate cancer deaths, the CPG model outperformed the 3 strata categories (C-Index 0.79 vs. 0.76, p<0.0001). The model also retained superior prognostic discrimination in treatment sub-groups - Radical prostatectomy (n=20,586): C-Index 0.77 vs. 074, radiotherapy (n=11,872): C-Index 0.73 vs. 0.68, and conservative management (n=14,950): C-Index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate (CPG2 vs. CPG3) and high-risk categories (CPG4 vs.CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p<0.0001). Conclusion: This validation study of nearly 75,000 men, confirms that the CPG 5-tiered prognostic model has superior discrimination in predicting prostate cancer death over the 3-tier model across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes We therefore propose adoption of the CPG model as a simple to use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer

SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts

Acknowledgements We sincerely thank the patients and family members who participated in this study. We would also like to thank Stefan Esher, Umeå University, for help with genealogy, and Anna Westerlund for excellent technical assistance. This work was supported by grants from the FOU, at the Umeå university hospital, and the Medical Faculty at Umeå University. The work at University of Gothenburg was supported by grants from The Swedish Research Council, the Swedish Rheumatism Association, the Royal 80-Year Fund of King Gustav V, ALF/LUA research grant from Sahlgrenska University Hospital in Gothenburg and the Lundberg Foundation. The work at the University of Gothenburg and the University of Aberdeen was supported by Euroclast, a Marie Curie FP7-People-2013-ITN: # 607446.Peer reviewedPublisher PD

Trends in mortality by labour market position around retirement ages in three European countries with different welfare regimes

&lt;p&gt;Objectives: In the face of economic downturn and increasing life expectancy, many industrial nations are adopting a policy of postponing the retirement age. However, questions still remain around the consequence of working longer into old age. We examine mortality by work status around retirement ages in countries with different welfare regimes; Finland (social democratic), Turin (Italy; conservative), and England and Wales (liberal).&lt;/p&gt; &lt;p&gt;Methods: Death rates and rate ratios (RRs) (reference rates = ‘in-work’), 1970 s–2000 s, were estimated for those aged 45–64 years using the England and Wales longitudinal study, Turin longitudinal study, and the Finnish linked register study.&lt;/p&gt; &lt;p&gt;Results: Mortality of the not-in-work was consistently higher than the in-work. Death rates for the not-in-work were lowest in Turin and highest in Finland. Rate ratios were smallest in Turin (RR men 1972–76 1.73; 2002–06 1.63; women 1.22; 1.68) and largest in Finland (RR men 1991–95 3.03; 2001–05 3.80; women 3.62; 4.11). Unlike RRs for men, RRs for women increased in every country (greatest in Finland).&lt;/p&gt; &lt;p&gt;Conclusions: These findings signal that overall, employment in later life is associated with lower mortality, regardless of welfare regime.&lt;/p&gt

Religious Identity, Religious Attendance, and Parental Control

Using a national sample of adolescents aged 10–18 years and their parents (N = 5,117), this article examines whether parental religious identity and religious participation are associated with the ways in which parents control their children. We hypothesize that both religious orthodoxy and weekly religious attendance are related to heightened levels of three elements of parental control: monitoring activities, normative regulations, and network closure. Results indicate that an orthodox religious identity for Catholic and Protestant parents and higher levels of religious attendance for parents as a whole are associated with increases in monitoring activities and normative regulations of American adolescents

Insulin-like growth factor-I and prostate cancer: a meta-analysis

Some, but not all, epidemiological found have shown that high circulating levels of insulin-like growth factor-I (IGF-I) are associated with an increased risk of prostate cancer. We performed a meta-analysis on all the studies reported so far to evaluate this association. In our Medline search, 14 case–control studies were identified. A standard protocol abstracted information for each study. Hedges' standardized mean difference (HSMD) and odds ratio (OR) were used to estimate the effect of IGF-I and IGF-binding proteins (IGFBP-3). The combined data showed that circulating levels of IGF-I were significantly higher in prostate cancer patients (HSMD = 0.194). The OR for prostate cancer was 1.47 (95% confidence interval (CI) 1.23–1.77) among men with high IGF-I compared to those with low IGF-I. The OR was 1.26 (95% CI 1.03–1.54) for IGFBP-3. Circulating levels of IGF-I and IGFBP-3 are likely to be higher in prostate cancer patients than in the controls. These findings support the suggestion that high IGF-I and IGFBP-3 are associated with an increased risk of prostate cancer. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Plasma phyto-oestrogens and prostate cancer in the European Prospective Investigation into Cancer and Nutrition

We examined plasma concentrations of phyto-oestrogens in relation to risk for subsequent prostate cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition. Concentrations of isoflavones genistein, daidzein and equol, and that of lignans enterolactone and enterodiol, were measured in plasma samples for 950 prostate cancer cases and 1042 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of these phyto-oestrogens were estimated by conditional logistic regression. Higher plasma concentrations of genistein were associated with lower risk of prostate cancer: RR among men in the highest vs the lowest fifth, 0.71 (95% confidence interval (CI) 0.53–0.96, P trend=0.03). After adjustment for potential confounders this RR was 0.74 (95% CI 0.54–1.00, P trend=0.05). No statistically significant associations were observed for circulating concentrations of daidzein, equol, enterolactone or enterodiol in relation to overall risk for prostate cancer. There was no evidence of heterogeneity in these results by age at blood collection or country of recruitment, nor by cancer stage or grade. These results suggest that higher concentrations of circulating genistein may reduce the risk of prostate cancer but do not support an association with plasma lignans