Proposal for a descriptive and differentiated presentation of the longitudinal impact of the new organized cancer screening guideline and HPV vaccination in Germany.

INTRODUCTION: Since 01/01/2020, the cervical cancer screening in Germany has been carried out due to the organized early cancer diagnosis guideline (oKFE-RL). In 2007, HPV vaccination was initiated in Germany. The main goal of both initiatives is to further reduce the incidence of invasive cervical cancer. To assess the effect of the new screening strategy in a timely manner, monitoring of short-term changes need to be considered. Ideally, the effects of both prevention methods would be presented together in one model. MATERIALS AND METHODS: Because no change in the incidence of invasive cervical cancer is initially expected, the incidence of CIN 3 is used as a surrogate parameter to assess the effects of the prevention efforts. Based on expected additional effects of vaccination and co-testing, a model-based estimation of the expected CIN 3 incidence during the evaluation of the screening program is performed using the CIN 3 incidence in the Saarland population. MODELING RESULTS: The oKFE-RL provides for two groups: Primary cytodiagnosis continues until 35 years of age. Here, in the next few years, CIN 3 incidence will be reduced not by the oKFE-RL but by the increasing proportion of vaccinated women. In the group over 35 years, co-testing was introduced with a stringent algorithm. Due to the higher sensitivity of the HPV test, significantly more CIN 3 are detected in the first round of 3 years and thus, the CIN 3 incidence initially increases. As these CIN 3 are absent in the second round, significantly fewer CIN 3 cases will be detected then. These effects suggest a global decrease in CIN 3 incidence of 25.8% after 6 years. CONCLUSION: Observation of the age distribution curve of CIN 3 allows both effects of prevention to be assessed in a timely manner and separately. In the future, data from epidemiologic cancer registries should be incorporated into the model to replace modeling with real data.

Prediction of clinical diagnosis of Alzheimer's disease, vascular, mixed, and all-cause dementia by a polygenic risk score and APOE status in a community-based cohort prospectively followed over 17 years.

The strongest genetic risk factor for Alzheimer's disease (AD) is the ε4 allele of Apolipoprotein E (APOE) and recent genome-wide association meta-analyses have confirmed additional associated genetic loci with smaller effects. The aim of this study was to investigate the ability of an AD polygenic risk score (PRS) and APOE status to predict clinical diagnosis of AD, vascular (VD), mixed (MD), and all-cause dementia in a community-based cohort prospectively followed over 17 years and secondarily across age, sex, and education strata. A PRS encompassing genetic variants reaching genome-wide significant associations to AD (excluding APOE) from the most recent genome-wide association meta-analysis data was calculated and APOE status was determined in 5203 participants. During follow-up, 103, 111, 58, and 359 participants were diagnosed with AD, VD, MD, and all-cause dementia, respectively. Prediction ability of AD, VD, MD, and all-cause dementia by the PRS and APOE was assessed by multiple logistic regression and receiver operating characteristic curve analyses. The PRS per standard deviation increase in score and APOE4 positivity (≥1 ε4 allele) were significantly associated with greater odds of AD (OR, 95% CI: PRS: 1.70, 1.45-1.99; APOE4: 3.34, 2.24-4.99) and AD prediction accuracy was significantly improved when adding the PRS to a base model of age, sex, and education (ASE) (c-statistics: ASE, 0.772; ASE + PRS, 0.810). The PRS enriched the ability of APOE to discern AD with stronger associations than to VD, MD, or all-cause dementia in a prospective community-based cohort.

Time trends in incidence and mortality of cutaneous melanoma in Germany.

OBJECTIVES: To characterize incidence and mortality trends of cutaneous melanoma (CM) in Germany to extrapolate these data until 2030. METHODS: We evaluated data from the Centre for Cancer Registry Data (1999-2012) and from the Saarland Cancer Registry (1970-2012). Age-standardized (according to the European Standard Population, WHO 1976) incidence and mortality rates [age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs)] and crude incidence and mortality rates [crude incidence rates (CIRs) and crude mortality rates (CMRs)] were analysed. RESULTS: In entire Germany, ASIRs increased by 55% to 19.2 and CIRs by 77% to 26.0 new cases per 100 000 from 1999 to 2012. ASMRs remained stable, whereas CMR increased by 58% to 4.1 for males and by 30% to 3.0 for females per 100 000. In the Federal State of Saarland, ASIRs increased more than four-fold to 13.1, CIRs increased six-seven fold to 18.5/100 000 from 1970 to 2012. In the same period, ASMRs increased three-fold in males and two-fold in females to 2.5 and 1.6, whereas CMRs increased 5.5-fold in males and 3.5-fold in females to 3.9 and 3.2/100 000, mainly caused by steep increases of CIRs and CMRs in age groups ≥60 years. Projected CIRs will rise to 44-46 for males and 38-40 for females in 2030. Steepest increases were extrapolated for patients ≥60 years, especially for males, but are also expected for age groups of 40-59 years. In contrast, CIRs are anticipated to stabilize for subjects <40 years. CONCLUSIONS: There is a constant increase in incidence and mortality rates for CM in Germany. As the German population is ageing and the current population has already accumulated high levels of UV exposure, a further increase in melanoma incidence is projected for the future without signs of levelling-off.

Trends in incidence and predictions of cutaneous melanoma across Europe up to 2015.

BACKGROUND: Melanoma is a significant health problem in Caucasian populations. The most recently available data from cancer registries often have a delay of several months up to a few years and they are generally not easily accessible. OBJECTIVES: To assess recent age- and sex-specific trends in melanoma incidence and make predictions for 2010 and 2015. METHODS: A retrospective registry-based analysis was performed with data from 29 European cancer registries. Most of them had data available from 1990 up to 2006/7. World-standardized incidence rates (WSR) and the estimated annual percentage change (EAPC) were computed. Predictions were based on linear projection models. RESULTS: Overall the incidence of melanoma is rapidly rising and will continue to do so. The incidence among women in Europe was generally higher than in men. The highest incidence rates were seen for Northern and north-western countries like the UK, Ireland and the Netherlands. The lowest incidence rates were observed in Portugal and Spain. The incidence overall remained stable in Norway, where, amongst young (25-49 years) Norwegian males rates significantly decreased (EAPC -2.8, 95% CI -3.6; -2.0). Despite a low melanoma incidence among persons above the age of 70, this age group experienced the greatest increase in risk during the study period. CONCLUSIONS: Incidence rates of melanoma are expected to continue rising. These trends are worrying in terms of disease burden, particularly in eastern European countries.

[Rising incidence of papillary thyroid carcinoma in Germany]. / Inzidenzzunahme des papillären Schilddrüsenkarzinoms in Deutschland.

BACKGROUND: The incidence of thyroid cancer (TC), a rare malignancy, has strongly risen in recent decades. Possible causes of this rise include increasing diagnostic activity, nuclear tests after World War II, and the Chernobyl disaster. AIM: This article presents the time trends of TC incidence between 2003 and 2008 in Germany according to histological tumor type and sex, and provides a description of TC incidence according to districts (Kreise) and sex in Germany. METHODS: Data on persons newly diagnosed with thyroid cancer (ICD-10 code, C73) between 2003 and 2008 were obtained from the Center of Cancer Registry Data at the Robert Koch Institute. Official population and mortality data were used. Age-specific and age-standardized incidence rates (ASIR) were calculated according to sex and tumor histology. RESULTS: Between 2003 and 2008, the ASIR of TC rose from 2.7 to 3.4 (men) and from 6.5 to 8.9 (women) per 100,000 per year. This rise can be almost completely attributed to the rising incidence of papillary TC. The steepest rise in frequency was observed in TNM-T1 tumors. A positive north-south gradient of TC incidence was found. DISCUSSION: The cause of the marked rise of TC incidence in recent decades is unknown. The positive north-south gradient of the TC incidence may possibly be attributed in part to long-standing differences of iodine intake between different German regions. CONCLUSION: An epidemiological study of the possible causes of the rising TC incidence and of the regional differences of TC incidence in Germany is recommended.

Testicular cancer in Europe and the USA: survival still rising among older patients.

BACKGROUND: Despite high curability, some testicular cancer (TC) patient groups may have increased mortality. We provide a detailed age- and histology-specific comparison of population-based relative survival of TC patients in Europe and the USA. Design Using data from 12 European cancer registries and the USA Surveillance, Epidemiology and End Results 9 database, we report survival trends for patients diagnosed with testicular seminomas and nonseminomas between 1993-1997 and 2003-2007. Additionally, a model-based analysis was used to compare survival trends and relative excess risk (RER) of death between Europe and the USA adjusting for differences in age and histology. RESULTS: In 2003-2007, the 5-year relative survival of patients with testicular seminoma was at least 98% among those aged <50 years, survival of patients with nonseminoma remained 3%-6% units lower. Despite improvements in the relative survival of nonseminoma patients aged ≥ 50 years by 13%-18% units, survival remained markedly lower than the survival of seminoma patients of the same age. Model-based analyses showed increased RERs for nonseminomas, older, and European patients. CONCLUSIONS: There remains little room for survival improvement among testicular seminoma patients, especially for those aged <50 years. Older TC patients remain at increased risk of death, which seems mainly attributable to the lower survival among the nonseminoma patients.

[Data quality or differences in oncological care? - standards of reporting for cancer survival analyses based on registry data]. / Datenqualität oder Unterschiede in der onkologischen Versorgung? - Berichtsstandards für Überlebenszeitanalysen mit Krebsregisterdaten.

BACKGROUND: The results of population-based cancer survival analyses are essential criteria with regard to the evaluation of oncological care. Their use and their interpretation as such require knowledge and transparency with regard to the data basis in order to avoid inadequate conclusions. METHOD: The working group 'survival analysis' of the Association of Population-Based Cancer Registries in Germany (GEKID) has identified factors within cancer registration and data evaluation which may distort population-based cancer survival analyses to a relevant degree. Recommendations in terms of standards of reporting were developed by mutual consent following empirical studies and discussions within GEKID. RESULTS: We provide a list of 17 indicators to be taken into account and to be presented within the scope of population-based survival analyses. CONCLUSIONS: Referring to the "standards of reporting concerning population-based cancer survival analyses" introduced by GEKID there is a proposal on data transparency on hand, which might contribute substantially to the assessability of outcome quality in oncological care.

Survival from colorectal cancer in Germany in the early 21st century.

BACKGROUND: Colorectal cancer is the most common cancer in Germany and the second most common cause of cancer-related deaths in both men and women. The aim of this study is to provide detailed analysis of recent developments in survival of colorectal cancer patients using newly available data on a national basis. METHODS: We included data from 11 German cancer registries covering a population of 33 million inhabitants. Period analysis and modelled period analysis were used to provide most up-to-date estimates of 5-year relative survival in 2002-2006. RESULTS: The analysis was based on records of 164 996 colorectal cancer patients. Five-year relative survival was 63.0% overall, decreased with age and was significantly higher among women than among men in patients under 75 years. Overall age-adjusted 5-year relative survival increased from 60.6 to 65.0% over the period 2002-2006. Significant increase in survival was only observed in patients with localised or regional disease. Highest subsite-specific survival was observed in patients with cancer in descending (67.7%) and ascending (66.5%) colon. CONCLUSION: Survival of patients with colorectal cancer continued to increase in the early 21st century in Germany, with 5-year relative survival reaching 65% in 2006. However, lack of progress still persisted in patients with advanced disease.

Survival from common and rare cancers in Germany in the early 21st century.

BACKGROUND: Until recently, population-based data of cancer survival in Germany mostly relied on one registry covering ∼1 million people (1.3% of the German population). Here, we provide up-to-date cancer survival estimates for Germany based on data from 11 population-based cancer registries, covering 33 million people and compare them to survival estimates from the United States. PATIENTS AND METHODS: Cancer patients diagnosed in 1997-2006 were included. Period analysis was employed to calculate 5-year relative survival for 38 cancers for 2002-2006. German and USA survival rates were compared utilizing the Surveillance, Epidemiology and End Results 13 database. RESULTS: Five-year relative survival >80% was observed for testicular cancer (93.5%), skin melanoma (89.4%), cancers of the prostate (89.1%) and thyroid (87.8%), Hodgkin's lymphoma (84.5%) and cancers of the breast (83.7%) and endometrium (81.0%), which together account for almost 40% of cases. For the majority of cancers, German survival estimates were close to or below those in the United States. Exceptions with higher survival in Germany were cancers of the stomach, pancreas and kidney and Hodgkin's lymphoma. CONCLUSIONS: German cancer survival estimates are mostly higher than the 2000-2002 pan-European estimates. Further research is needed to investigate causes responsible for differences between German and USA cancer survival rates.

Changes in incidence, survival and mortality of prostate cancer in Europe and the United States in the PSA era: additional diagnoses and avoided deaths.

BACKGROUND: We describe changes in prostate cancer incidence, survival and mortality and the resulting impact in additional diagnoses and avoided deaths in European areas and the United States. METHODS: Using data from 12 European cancer registries and the Surveillance, Epidemiology and End Results program, we describe changes in prostate cancer epidemiology between the beginning of the PSA era (USA: 1985-1989, Europe: 1990-1994) and 2002-2006 among patients aged 40-64, 65-74, and 75+. Additionally, we examine changes in yearly numbers of diagnoses and deaths and variation in male life expectancy. RESULTS: Incidence and survival, particularly among patients aged <75, increased dramatically, yet both remain (with few exceptions in incidence) lower in Europe than in the United States. Mortality reductions, ongoing since the mid/late 1990 s, were more consistent in the United States, had a distressingly small absolute impact among patients aged 40-64 and the largest absolute impact among those aged 75+. Overall ratios of additional diagnoses/avoided deaths varied between 3.6 and 27.6, suggesting large differences in the actual impact of prostate cancer incidence and mortality changes. Ten years of remaining life expectancy was reached between 68 and 76 years. CONCLUSION: Policies reflecting variation in population life expectancy, testing preferences, decision aids and guidelines for surveillance-based management are urgently needed.

Up-to-date results on survival of patients with melanoma in Germany.

BACKGROUND: Prior analyses of survival of patients with primary cutaneous malignant melanoma from Germany were based only on small populations and need to be updated. OBJECTIVES: We give a detailed overview of relative 5-year survival by sex, age group, histology, tumour stage and body site, and of time trends in a population of 33 million (40% of Germany), and compare survival in the federal states. METHODS: Conventional and model-based period analysis using the Ederer II method was applied to patients with melanoma diagnosed during 1997-2006 in Germany to assess 5-year relative survival (RS) rates and time trends. RESULTS: In total, 37,155 melanoma cases were included. Overall age-adjusted 5-year RS for the time period 2002-2006 was 91·9% for women and 87·0% for men. Survival differences by age group, histology, tumour stage and body site were found. No significant overall trend (2002-2006) was seen either in women or in men. Differences in survival between federal states were small; no clear pattern was seen. CONCLUSIONS: Based on the most recent and high-quality data from population-based cancer registries a comprehensive picture on melanoma survival in Germany was given. Survival from cutaneous malignant melanoma was high compared with other cancer sites and did not change during the analysed period 2002-2006. Patterns in melanoma survival by sex, age, tumour stage, histology and body site were in good agreement with previously published findings. No relevant differences between federal states were found.

New malignancies following cancer of the urinary bladder: analysis of German cancer registry data.

This analysis aimed at occurrence and distribution patterns of new malignancies following bladder cancer. Standardised incidence ratios (SIRs) were calculated for two German population-based cancer registries of North Rhine-Westphalia (NRW) and Saarland to access risks for subsequent primaries. An elevated risk for secondary cancer of any site but urothelium was observed in NRW men [SIR 1.35, 95% confidence interval (CI) 1.22-1.49]. The corresponding risk in Saarland was not significantly elevated (SIR 1.06, 95% CI 0.97-1.15). In data of both registries excess risks were observed for cancer of the respiratory tract (SIR 1.54, CI 1.23-1.89 in NRW men) and the prostate (SIR 1.91, 95% CI 1.61-2.24 in NRW; SIR 1.25, 95% CI 1.07-1.45 in Saarland). Common risk factors and incidental findings during follow-up care of bladder cancer patients might explain most of the observed patterns. In addition SIRs were throughout particular high for subsequent cancer of the renal pelvis and the ureter due to pathological characteristics of urothelial neoplasms.

Cancer risk in HIV-infected individuals on HAART is largely attributed to oncogenic infections and state of immunocompetence.

OBJECTIVES: To estimate the cancer risk of HIV-infected patients in the HAART era with respect to a general reference population and to determine risk factors for malignancy. METHODS: Long term (1996-2009) cancer incidence of the Bonn single centre HIV cohort was compared to the incidence of the reference population of Saarland using standardized incidence ratios (SIR). Poisson regression analysis was used to identify predictors of cancer risk. RESULTS: 1,476 patients entered the cohort, enabling 8,772 person years of observation. 121 tumours in 114 patients, 7 in-situ and 114 invasive cancers, were identified. Malignancies associated with infectious agents such as Kaposi sarcoma (SIRs: male: 5,683; female: 277), non-Hodgkin lymphoma (SIRs male: 35; female: 18), anal cancer (SIRs male: 88; female: 115) as well a cervical carcinoma (SIR female: 4) and Hodgkin?s disease (SIR male: 39) and liver cancer (SIR male: 18) were substantially more frequent in HIV-infected patients than in the general population (p< 0.001, each), whereas all other types of cancer were not increased. Poisson regression identified HAART (incidence rate ratio IRR (95% CI): 0.28 (0.19-0.41), p<0.001), CD4 count (IRR per 100 cells/µl increase: 0.66 (0.57-0.76), p<0.001), hepatitis B (IRR: 2.15 (1.10-4.20), p = 0.046) and age (IRR per 10 year increase: 1.23 (1.03 - 1.46), p = 0.023) as independent predictors for the occurrence of any type of cancer. CONCLUSIONS: HAART and preserved CD4 cells preferentially reduce the risk of malignancies associated with oncogenic infections.

[Population-based incidence rates of colorectal neoplasms (2000 - 2006) - has systematic colonoscopy screening an impact on incidence? A combined analysis of cancer registry data of the Federal States of Bremen, Hamburg, Saarland and Schleswig-Holstein]. / Bevölkerungsbezogene Darmkrebsinzidenz im Zeitraum 2000 bis 2006 - Deuten sich erste Auswirkungen des Koloskopie-Screenings an? Eine gemeinsame Auswertung der Krebsregisterdaten aus Bremen, Hamburg, dem Saarland und Schleswig-Holstein.

BACKGROUND: A quality assured colonoscopy screening was implemented in Germany in the year 2002. Persons aged 55 years or older with a health insurance are eligible. The primary aim of colonoscopy screening is the early detection of cancer. Furthermore, an incidence decrease is expected due to systematic adenomectomy. Up to date, neither a systematic monitoring of epidemiological data nor a mortality evaluation has been contracted by law. MATERIALS AND METHODS: Four population-based cancer registries of the federal states Bremen, Hamburg, Saarland, and Schleswig-Holstein in Germany provided incidence data on colorectal cancers during 2000 - 2006. Age-standardised and stage-specific incidence rates and time trends (Joinpoint analysis and APC method) are reported. RESULTS: Overall 34,100 colorectal cancers were registered, of which 91 % were within the screening-eligible age group. The incidence rise of in situ-cancers of the colon and rectum was significant. Changes in tumours of the T 3- and T 4-categories were not consistent. DISCUSSION: There seems to be a temporal linkage between the implementation of a quality assured colonoscopy screening and the epidemiology of colorectal cancers in Germany. The observed changes cannot be attributed definitively to the screening activities, because required data are not available on the population level. A linkage of screenees and cancer data from registered tumour patients, which allows an individual follow-up and a mortality evaluation, would be desirable.

[Cancer survival analysis in Germany--heading towards representative and comparable findings]. / Überlebenschancen von Krebspatienten in Deutschland--auf dem Weg zu repräsentativen, vergleichbaren Aussagen.

Cancer is an important issue within the German health care system with an estimated annual number of 435 000 incident cases and almost 210 000 deaths. Data of population-based cancer registries enable us to identify improvements of survival in oncological patients due to progress in therapeutic care and secondary prevention, as well as to investigate regional and international differences of this outcome. Comparing cancer survival rates, however, requires considering the impact of both methodical approaches and data quality. Potential factors of influence like algorithms, reference population, completeness of case ascertainment and quality of follow-up are discussed. For the first time harmonized proceedings are recommended in order to achieve comparability of population-based cancer survival rates in Germany.

Differences in incidence and survival of oral cavity and pharyngeal cancers between Germany and the United States depend on the HPV-association of the cancer site.

INTRODUCTION: The epidemiology of squamous cell oral cavity and pharyngeal cancers (OCPC) has changed rapidly during the last years, possibly due to an increase of human papilloma virus (HPV) positive tumors and successes in tobacco prevention. Here, we compare incidence and survival of OCPC by HPV-relation of the site in Germany and the United States (US). MATERIALS AND METHODS: Age-standardized and age-specific incidence and 5-year relative survival was estimated using data from population-based cancer registries in Germany and the US Surveillance Epidemiology and End Results (SEER) 13 database. Incidence was estimated for each year between 1999 and 2013. Relative survival for 2002-2005, 2006-2009, and 2010-2013 was estimated using period analysis. RESULTS: The datasets included 52,787 and 48,861 cases with OCPC diagnosis between 1997 and 2013 in Germany and the US. Incidence was much higher in Germany compared to the US for HPV-unrelated OCPC and more recently also for HPV-related OCPC in women. Five-year relative survival differences between Germany and the US were small for HPV-unrelated OCPC. For HPV-related OCPC, men had higher survival in the US (62.1%) than in Germany (45.4%) in 2010-2013. These differences increased over time and were largest in younger patients and stage IV disease without metastasis. In contrast, women had comparable survival for HPV-related OCPC in both countries. CONCLUSIONS: Strong survival differences between Germany and the US were observed for HPV-related OCPC in men, which might be explained by differences in HPV-attributable proportions. Close monitoring of the epidemiology of OCPC in each country is needed.

Implications from Under-reporting at Lifetime, Death Certificate Notifications and Trace-back on the Recorded Incidence of a "Newly" Established Population-based Cancer Registry.

OBJECTIVES: Population-based cancer registries (CRs) are powerful tools for measuring cancer burden and progress against cancer. The study's objective was to investigate the effects of under-reporting at lifetime, death certificate notifications, and trace-back on the incidence a newly established population-based CR may record during its initial 15 years of operation. METHODS: Using cancer data of nine CRs of the SEER programme we performed model calculations to investigate temporal trends of the recorded incidence that might be expected if registration started in 1995 with gradually increasing proportions of cancers reported to the CR. It was assumed that the CR obtains all death certificates providing cancer as the underlying cause of death. Different scenarios with regard to the development of the proportions of cancers reported to the CR and the use of trace-back were evaluated. RESULTS: Our model calculations demonstrated that the inclusion of cancers notified from death certificates which were diagnosed prior to the start of registration and which attribute to the incidence estimates of the year of death ('prevalent' cases) may compensate under-reporting typically observed right after the start of a CR. The recorded incidence may even be overestimated during the first years of registration, if large amounts of prevalent cancers are notified from death certificates (e.g. overestimation of lung cancer incidence by 8% and 21% in the first year of registration, if the proportions of cases reported were 50% and 70% in that year, overestimation of myeloma incidence still exceeding 5% after eight years of registration, if the proportion of cases reported to the CR had reached 97.5% after six years). Trace-back may effectively reduce the recorded surplus cancer cases. CONCLUSIONS: During the initial years of registration, the inclusion of prevalent cancers from death certificates may compensate the higher amount of underreporting right after the start of a CR. Accurate incidence estimates may nevertheless be observed for highly fatal cancers if substantial proportions of cancer cases are missed at lifetime, however apparent incidence trends observed in the initial years of registration need to be interpreted with caution.

Survival for oesophageal, stomach and small intestine cancers in Europe 1999-2007: Results from EUROCARE-5.

BACKGROUND: European regional variation in cancer survival was reported in the EUROCARE-4 study for patients diagnosed in 1995-1999. Relative survival (RS) estimates are here updated for patients diagnosed with cancer of the oesophagus, stomach and small intestine from 2000 to 2007. Trends in RS from 1999-2001 to 2005-2007 are presented to monitor and discuss improvements in patient survival in Europe. MATERIALS AND METHODS: EUROCARE-5 data from 29 countries (87 cancer registries) were used to investigate 1- and 5-year RS. Using registry-specific life-tables stratified by age, gender and calendar year, age-standardised 'complete analysis' RS estimates by country and region were calculated for Northern, Southern, Eastern and Central Europe, and for Ireland and United Kingdom (UK). Survival trends of patients in periods 1999-2001, 2002-2004 and 2005-2007 were investigated using the 'period' RS approach. We computed the 5-year RS conditional on surviving the first year (5-year conditional survival), as the ratio of age-standardised 5-year RS to 1-year RS. RESULTS: Oesophageal cancer 1- and 5-year RS (40% and 12%, respectively) remained poor in Europe. Patient survival was worst in Eastern (8%), Northern (11%) and Southern Europe (10%). Europe-wide, there was a 3% improvement in oesophageal cancer 5-year survival by 2005-2007, with Ireland and the UK (3%), and Central Europe (4%) showing large improvements. Europe-wide, stomach cancer 5-year RS was 25%. Ireland and UK (17%) and Eastern Europe (19%) had the poorest 5-year patient survival. Southern Europe had the best 5-year survival (30%), though only showing an improvement of 2% by 2005-2007. Small intestine cancer 5-year RS for Europe was 48%, with Central Europe having the best (54%), and Ireland and UK the poorest (37%). Five-year patient survival improvement for Europe was 8% by 2005-2007, with Central, Southern and Eastern Europe showing the greatest increases (⩾9%). CONCLUSIONS: Survival for these cancer sites, particularly oesophageal cancer, remains poor in Europe with wide variation. Further investigation into the wide variation, including analysis by histology and anatomical sub-site, will yield insights to better monitor and explain the improvements in survival observed over time.

Serum 25-hydroxyvitamin D and incidence of fatal and nonfatal cardiovascular events: a prospective study with repeated measurements.

CONTEXT: Several studies suggested that low serum concentrations of 25-hydroxyvitamin D (25(OH)D) are associated with an increased risk of cardiovascular disease (CVD). However, the evidence is still inconclusive, mostly based on CVD mortality and studies with single 25(OH)D measurements. OBJECTIVE: We aimed to assess the association of 25(OH)D with fatal and nonfatal CVD in the same study population, using repeated 25(OH)D measurements and competing risks analysis. DESIGN: This was a population-based cohort study (ESTHER study, baseline 2000-2002). Follow-up data, including survival status, were collected after 2, 5, and 8 years. The response rate for survival was 99.9%. SETTING: Participants were recruited during a health screening examination by their general practitioners. 25(OH)D was measured in blood samples collected at baseline and the 5-year follow-up visit. PATIENTS OR OTHER PARTICIPANTS: A total of 9949 men and women, aged 50 to 74 years at baseline, with sufficient knowledge of the German language and resident in the German state of Saarland were included in the study. MAIN OUTCOME MEASURES: Outcomes included CVD, coronary heart disease (CHD), and stroke, in total and differentiated into fatal and nonfatal events. RESULTS: Overall, 854 study participants had a nonfatal and 176 a fatal CVD event during 8 years of follow-up. Comparing subjects with 25(OH)D levels below 30 nmol/L and above 50 nmol/L resulted in a hazard ratio of 1.27 (95% confidence interval = 1.05-1.54) for total CVD and 1.62 (95% confidence interval = 1.07-2.48) for fatal CVD in a model adjusted for important potential confounders. No significant association for nonfatal CVD was observed. In dose-response analysis, we observed an increased cardiovascular risk at 25(OH)D levels below 75 nmol/L. Results for CHD and stroke were comparable to the results obtained for the composite outcome CVD. CONCLUSIONS: Our results support evidence that low 25(OH)D levels are associated with moderately increased risk of CVD and indicate that the observed association is much stronger for fatal than for nonfatal events.