NCALD as a potential predictive biomarker for the efficacy of platinum-based chemotherapy in ovarian cancer.

Aim: Since reliable response predictors to platinum-based chemotherapy in ovarian cancer (OC) are scarce, we characterize NCALD as a predictive biomarker. Materials & methods: NCALD mRNA (n = 100) and protein (n = 102) expression was analyzed in OC samples and associated with patient outcome. A stable OC cell line knockdown was generated and cellular response to platinum was explored. Results: High NCALD mRNA and protein expression was significantly associated with longer overall patient survival (p = 0.037/0.002). Knockdown experiments revealed a significant association between cisplatin sensitivity and NCALD expression. Conclusion: Low NCALD expression was associated with reduced sensitivity to platinum-based chemotherapy. NCALD may be a new biomarker candidate to identify patients who might benefit from platinum-based chemotherapy.

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

Physical activity and Mediterranean diet as potential modulators of osteoprotegerin and soluble RANKL in gBRCA1/2 mutation carriers: results of the lifestyle intervention pilot study LIBRE-1.

PURPOSE: Emerging evidence suggests that the progesterone-mediated receptor activator of nuclear factor κB (RANK)/soluble RANK ligand (sRANKL)/osteoprotegerin (OPG) pathway plays an important role in mammary carcinogenesis and is hyperactivated in germline (g)BRCA1/2 mutation carriers. We analyzed the effects of a 3-month intensive lifestyle intervention within the LIBRE-1 study on the serum levels of OPG and sRANKL and hypothesized that the intervention program provides a beneficial impact on the biomarkers by increasing OPG and reducing sRANKL serum concentrations. METHODS: Serum levels of OPG and sRANKL of 49 gBRCA1/2 mutation carriers were quantified using enzyme-linked immunosorbent assays. We used previously collected blood samples from participants of the prospective LIBRE-1 study, who were randomized into an intervention group (IG), increasing physical activity and adherence to the Mediterranean diet (MedD) through supervised sessions from study entry to the first study visit after 3 months and a usual-care control group (CG). Differences in biomarker levels before and after the 3-month intervention were tested within and between study groups. RESULTS: The lifestyle intervention resulted in a significant increase in OPG for participants in both the IG (q = 0.022) and CG (q = 0.002). sRANKL decreased significantly in the IG (q = 0.0464) and seemed to decrease in the CG (q = 0.5584). An increase in the intake of Omega-3 polyunsaturated fatty acids was significantly associated with an increase in OPG (r = 0.579, q = 0.045). Baseline serum levels of sRANKL were a strong predictor for the change of sRANKL in the course of the intervention (ß-estimate = - 0.70; q = 0.0018). Baseline physical fitness (assessed as VO2peak) might predict the change of OPG in the course of the intervention program (ß-estimate = 0.133 pg/ml/ml/min/kg; p = 0.0319; q = 0.2871). CONCLUSION: Findings from this pilot study seem to confirm our hypothesis by showing an increase in OPG and decrease in sRANKL over a 3-month lifestyle intervention and suggest that increased physical activity and adherence to the MedD are potent modulators of the biomarkers OPG and potentially sRANKL.

Estimating the Breast Cancer Burden in Germany and Implications for Risk-based Screening.

In Germany, it is currently recommended that women start mammographic breast cancer screening at age 50. However, recently updated guidelines state that for women younger than 50 and older than 70 years of age, screening decisions should be based on individual risk. International clinical guidelines recommend starting screening when a woman's 5-year risk of breast cancer exceeds 1.7%. We thus compared the performance of the current age-based screening practice with an alternative risk-adapted approach using data from a German population representative survey. We found that 10,498,000 German women ages 50-69 years are eligible for mammographic screening based on age alone. Applying the 5-year risk threshold of 1.7% to individual breast cancer risk estimated from a model that considers a woman's reproductive and personal characteristics, 39,000 German women ages 40-49 years would additionally be eligible. Among those women, the number needed to screen to detect one breast cancer case, NNS, was 282, which was close to the NNS = 292 among all 50- to 69-year-old women. In contrast, NNS = 703 for the 113,000 German women ages 50-69 years old with 5-year breast cancer risk <0.8%, the median 5-year breast cancer risk for German women ages 45-49 years, which we used as a low-risk threshold. For these low-risk women, longer screening intervals might be considered to avoid unnecessary diagnostic procedures. In conclusion, we show that risk-adapted mammographic screening could benefit German women ages 40-49 years who are at elevated breast cancer risk and reduce cost and burden among low-risk women ages 50-69 years. PREVENTION RELEVANCE: We show that a risk-based approach to mammography screening for German women can help detect breast cancer in women ages 40-49 years with increased risk and reduce screening costs and burdens for low-risk women ages 50-69 years. However, before recommending a particular implementation of a risk-based mammographic screening approach, further investigations of models and thresholds used are needed.

PALLD mutation in a European family conveys a stromal predisposition for familial pancreatic cancer.

BACKGROUNDPancreatic cancer is one of the deadliest cancers, with low long-term survival rates. Despite recent advances in treatment, it is important to identify and screen high-risk individuals for cancer prevention. Familial pancreatic cancer (FPC) accounts for 4%-10% of pancreatic cancers. Several germline mutations are related to an increased risk and might offer screening and therapy options. In this study, we aimed to identity of a susceptibility gene in a family with FPC.METHODSWhole exome sequencing and PCR confirmation was performed on the surgical specimen and peripheral blood of an index patient and her sister in a family with high incidence of pancreatic cancer, to identify somatic and germline mutations associated with familial pancreatic cancer. Compartment-specific gene expression data and immunohistochemistry were also queried.RESULTSThe identical germline mutation of the PALLD gene (NM_001166108.1:c.G154A:p.D52N) was detected in the index patient with pancreatic cancer and the tumor tissue of her sister. Whole genome sequencing showed similar somatic mutation patterns between the 2 sisters. Apart from the PALLD mutation, commonly mutated genes that characterize pancreatic ductal adenocarcinoma were found in both tumor samples. However, the 2 patients harbored different somatic KRAS mutations (G12D and G12V). Healthy siblings did not have the PALLD mutation, indicating a disease-specific impact. Compartment-specific gene expression data and IHC showed expression in cancer-associated fibroblasts (CAFs).CONCLUSIONWe identified a germline mutation of the palladin (PALLD) gene in 2 siblings in Europe, affected by familial pancreatic cancer, with a significant overexpression in CAFs, suggesting that stromal palladin could play a role in the development, maintenance, and/or progression of pancreatic cancer.FUNDINGDFG SFB 1321.

TP53 germline mutations in the context of families with hereditary breast and ovarian cancer: a clinical challenge.

PURPOSE: TP53germline (g) mutations, associated with the Li-Fraumeni syndrome (LFS), have rarely been reported in the context of hereditary breast and ovarian cancer (HBOC). The prevalence and cancer risks in this target group are unknown and counseling remains challenging. Notably an extensive high-risk surveillance program is implemented, which evokes substantial psychological discomfort. Emphasizing the lack of consensus about clinical implications, we aim to further characterize TP53g mutations in HBOC families. METHODS: Next-generation sequencing was conducted on 1876 breast cancer (BC) patients who fulfilled the inclusion criteria for HBOC. RESULTS: (Likely) pathogenic variants in TP53 gene were present in 0.6% of the BC cohort with higher occurrence in early onset BC < 36 years. (1.1%) and bilateral vs. unilateral BC (1.1% vs. 0.3%). Two out of eleven patients with a (likely) pathogenic TP53g variant (c.542G > A; c.375G > A) did not comply with classic LFS/Chompret criteria. Albeit located in the DNA-binding domain of the p53-protein and therefore revealing no difference to LFS-related variants, they only displayed a medium transactivity reduction constituting a retainment of wildtype-like anti-proliferative functionality. CONCLUSION: Among our cohort of HBOC families, we were able to describe a clinical subgroup, which is distinct from the classic LFS-families. Strikingly, two families did not adhere to the LFS criteria, and functional analysis revealed a reduced impact on TP53 activity, which may suit to the attenuated phenotype. This is an approach that could be useful in developing individualized screening efforts for TP53g mutation carrier in HBOC families. Due to the low incidence, national/international cooperation is necessary to further explore clinical implications. This might allow providing directions for clinical recommendations in the future.

Performance of Breast Cancer Polygenic Risk Scores in 760 Female CHEK2 Germline Mutation Carriers.

BACKGROUND: Genome-wide association studies suggest that the combined effects of breast cancer (BC)-associated single nucleotide polymorphisms (SNPs) can improve BC risk stratification using polygenic risk scores (PRSs). The performance of PRSs in genome-wide association studies-independent clinical cohorts is poorly studied in individuals carrying mutations in moderately penetrant BC predisposition genes such as CHEK2. METHODS: A total of 760 female CHEK2 mutation carriers were included; 561 women were affected with BC, of whom 74 developed metachronous contralateral BC (mCBC). For PRS calculations, 2 SNP sets covering 77 (SNP set 1, developed for BC risk stratification in women unselected for their BRCA1/2 germline mutation status) and 88 (SNP set 2, developed for BC risk stratification in female BRCA1/2 mutation carriers) BC-associated SNPs were used. All statistical tests were 2-sided. RESULTS: Both SNP sets provided concordant PRS results at the individual level (r = 0.91, P < 2.20 × 10-16). Weighted cohort Cox regression analyses revealed statistically significant associations of PRSs with the risk for first BC. For SNP set 1, a hazard ratio of 1.71 per SD of the PRS was observed (95% confidence interval = 1.36 to 2.15, P = 3.87 × 10-6). PRSs identify a subgroup of CHEK2 mutation carriers with a predicted lifetime risk for first BC that exceeds the surveillance thresholds defined by international guidelines. Association of PRS with mCBC was examined via Cox regression analysis (SNP set 1 hazard ratio = 1.23, 95% confidence interval = 0.86 to 1.78, P = .26). CONCLUSIONS: PRSs may be used to personalize risk-adapted preventive measures for women with CHEK2 mutations. Larger studies are required to assess the role of PRSs in mCBC predisposition.

Toward targeted prevention: risk factors for prediabetes defined by impaired fasting glucose, impaired glucose tolerance and increased HbA1c in the population-based KORA study from Germany.

AIMS: To identify socioeconomic, behavioral and clinical factors that are associated with prediabetes according to different prediabetes definition criteria. METHODS: Analyses use pooled data of the population-based Cooperative Health Research in the Region of Augsburg (KORA) studies (n = 5312 observations aged ≥ 38 years without diabetes). Prediabetes was defined through either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or elevated HbA1c according to thresholds of the American Diabetes Association. Explanatory variables were regressed on prediabetes using generalized estimating equations. RESULTS: Mean age was 58.4 years; 50% had prediabetes (33% had IFG, 16% IGT, and 26% elevated HbA1c, 10% fulfilled all three criteria). Age, obesity, hypertension, low education, unemployment, statutory health insurance, urban residence and physical inactivity were associated with prediabetes. Male sex was a stronger risk factor for IFG (OR = 2.5; 95%-CI: 2.2-2.9) than for IGT or elevated HbA1c, and being unemployed was a stronger risk factor for IGT (OR = 3.2 95%-CI: 2.6-4.0) than for IFG or elevated HbA1c. CONCLUSIONS: The overlap of people with IFG, IGT and elevated HbA1c is small, and some factors are associated with only one criterion. Knowledge on sociodemographic and socioeconomic risk factors can be used to effectively target interventions to people at high risk for type 2 diabetes.

Validation of two US breast cancer risk prediction models in German women.

PURPOSE: There are no models for German women that predict absolute risk of invasive breast cancer (BC), i.e., the probability of developing BC over a prespecified time period, given a woman's age and characteristics, while accounting for competing risks. We thus validated two absolute BC risk models (BCRAT, BCRmod) developed for US women in German women. BCRAT uses a woman's medical, reproductive, and BC family history; BCRmod adds modifiable risk factors (body mass index, hormone replacement therapy and alcohol use). METHODS: We assessed model calibration by comparing observed BC numbers (O) to expected numbers (E) computed from BCRmod/BCRAT for German women enrolled in the prospective European Prospective Investigation into Cancer and Nutrition (EPIC), and after updating the models with German BC incidence/competing mortality rates. We also compared 1-year BC risk predicted for all German women using the German Health Interview and Examination Survey for Adults (DEGS) with overall German BC incidence. Discriminatory performance was quantified by the area under the receiver operator characteristics curve (AUC). RESULTS: Among 22,098 EPIC-Germany women aged 40+ years, 745 BCs occurred (median follow-up: 11.9 years). Both models had good calibration for total follow-up, EBCRmod/O = 1.08 (95% confidence interval: 0.95-1.21), and EBCRAT/O = 0.99(0.87-1.11), and over 5 years. Compared to German BC incidence rates, both models somewhat overestimated 1-year risk for women aged 55+ and 70+ years. For total follow-up, AUCBCRmod = 0.61(0.58-0.63) and AUCBCRAT = 0.58(0.56-0.61), with similar values for 5-year follow-up. CONCLUSION: US BC risk models showed adequate calibration in German women. Discriminatory performance was comparable to that in US women. These models thus could be applied for risk prediction in German women.

Epidemiologic Risk Factors in a Comparison of a Barrett Esophagus Registry (BarrettNET) and a Case-Control Population in Germany.

Endoscopic screening for Barrett's esophagus as the major precursor lesion for esophageal adenocarcinoma is mostly offered to patients with symptoms of gastroesophageal reflux disease (GERD). However, other epidemiologic risk factors might affect the development of Barrett's esophagus and esophageal adenocarcinoma. Therefore, efforts to improve the efficiency of screening to find the Barrett's esophagus population "at risk" compared with the normal population are needed. In a cross-sectional analysis, we compared 587 patients with Barrett's esophagus from the multicenter German BarrettNET registry to 1976 healthy subjects from the population-based German KORA cohort, with and without GERD symptoms. Data on demographic and lifestyle factors, including age, gender, smoking, alcohol consumption, body mass index, physical activity, and symptoms were collected in a standardized epidemiologic survey. Increased age, male gender, smoking, heavy alcohol consumption, low physical activity, low health status, and GERD symptoms were significantly associated with Barrett's esophagus. Surprisingly, among patients stratified for GERD symptoms, these associations did not change. Demographic, lifestyle, and clinical factors as well as GERD symptoms were associated with Barrett's esophagus development in Germany, suggesting that a combination of risk factors could be useful in developing individualized screening efforts for patients with Barrett's esophagus and GERD in Germany.

Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance.

Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1-56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2-19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8-6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4-12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk.

Modifying effect of metabotype on diet-diabetes associations.

PURPOSE: Inter-individual metabolic differences may be a reason for previously inconsistent results in diet-diabetes associations. We aimed to investigate associations between dietary intake and diabetes for metabolically homogeneous subgroups ('metabotypes') in a large cross-sectional study. METHODS: We used data of 1517 adults aged 38-87 years from the German population-based KORA FF4 study (2013/2014). Dietary intake was estimated based on the combination of a food frequency questionnaire and multiple 24-h food lists. Glucose tolerance status was classified based on an oral glucose tolerance test in participants without a previous diabetes diagnosis using American Diabetes Association criteria. Logistic regression was applied to examine the associations between dietary intake and diabetes for two distinct metabotypes, which were identified based on 16 biochemical and anthropometric parameters. RESULTS: A low intake of fruits and a high intake of total meat, processed meat and sugar-sweetened beverages (SSB) were significantly associated with diabetes in the total study population. Stratified by metabotype, associations with diabetes remained significant for intake of total meat (OR 1.67, 95% CI 1.04-2.67) and processed meat (OR 2.23, 95% CI 1.24-4.04) in the metabotypes with rather favorable metabolic characteristics, and for intake of fruits (OR 0.83, 95% CI 0.68-0.99) and SSB (OR:1.21, 95% CI 1.09-1.35) in the more unfavorable metabotype. However, only the association between SSB intake and diabetes differed significantly by metabotype (p value for interaction = 0.01). CONCLUSIONS: Our findings suggest an influence of metabolic characteristics on diet-diabetes associations, which may help to explain inconsistent previous results. The causality of the observed associations needs to be confirmed in prospective and intervention studies.

BarrettNET-a prospective registry for risk estimation of patients with Barrett's esophagus to progress to adenocarcinoma.

Risk stratification in patients with Barrett's esophagus (BE) to prevent the development of esophageal adenocarcinoma (EAC) is an unsolved task. The incidence of EAC and BE is increasing and patients are still at unknown risk. BarrettNET is an ongoing multicenter prospective cohort study initiated to identify and validate molecular and clinical biomarkers that allow a more personalized surveillance strategy for patients with BE. For BarrettNET participants are recruited in 20 study centers throughout Germany, to be followed for progression to dysplasia (low-grade dysplasia or high-grade dysplasia) or EAC for >10 years. The study instruments comprise self-administered epidemiological information (containing data on demographics, lifestyle factors, and health), as well as biological specimens, i.e., blood-based samples, esophageal tissue biopsies, and feces and saliva samples. In follow-up visits according to the individual surveillance plan of the participants, sample collection is repeated. The standardized collection and processing of the specimen guarantee the highest sample quality. Via a mobile accessible database, the documentation of inclusion, epidemiological data, and pathological disease status are recorded subsequently. Currently the BarrettNET registry includes 560 participants (23.1% women and 76.9% men, aged 22-92 years) with a median follow-up of 951 days. Both the design and the size of BarrettNET offer the advantage of answering research questions regarding potential causes of disease progression from BE to EAC. Here all the integrated methods and materials of BarrettNET are presented and reviewed to introduce this valuable German registry.

Is risk-stratified breast cancer screening economically efficient in Germany?

OBJECTIVES: Risk stratification has so far been evaluated under the assumption that women fully adhere to screening recommendations. However, the participation in German cancer screening programs remains low at 54%. The question arises whether risk-stratified screening is economically efficient under the assumption that adherence is not perfect. METHOD: We have adapted a micro-simulation Markov model to the German context. Annual, biennial, and triennial routine screening are compared with five risk-adapted strategies using thresholds of relative risk to stratify screening frequencies. We used three outcome variables (mortality reduction, quality-adjusted life years, and false-positive results) under the assumption of full adherence vs. an adherence rate of 54%. Strategies are evaluated using efficiency frontiers and probabilistic sensitivity analysis (PSA). RESULTS: The reduced adherence rate affects both performance and cost; incremental cost-effectiveness ratios remain constant. The results of PSA show that risk-stratified screening strategies are more efficient than biennial routine screening under certain conditions. At any willingness-to-pay (WTP), there is a risk-stratified alternative with a higher likelihood of being the best choice. However, without explicit decision criteria and WTP, risk-stratified screening is not more efficient than biennial routine screening. Potential improvements in the adherence rates have significant health gains and budgetary implications. CONCLUSION: If the participation rate for mammographic screening is as low as in Germany, stratified screening is not clearly more efficient than routine screening but dependent on the WTP. A more promising design for future stratified strategies is the combination of risk stratification mechanisms with interventions to improve the low adherence in selected high-risk groups.

High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer.

PURPOSE: To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). METHODS: A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age. RESULTS: A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9-93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6-85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6-91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5‰ (95% CI 29.8-62.9) for the first screening round in BRCA2 carriers to 2.9‰ (95% CI 1.3-6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years. CONCLUSIONS: High-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients.

Personalized Mammography Screening and Screening Adherence-A Simulation and Economic Evaluation.

OBJECTIVE: Personalized breast cancer screening has so far been economically evaluated under the assumption of full screening adherence. This is the first study to evaluate the effects of nonadherence on the evaluation and selection of personalized screening strategies. METHODS: Different adherence scenarios were established on the basis of findings from the literature. A Markov microsimulation model was adapted to evaluate the effects of these adherence scenarios on three different personalized strategies. RESULTS: First, three adherence scenarios describing the relationship between risk and adherence were identified: 1) a positive association between risk and screening adherence, 2) a negative association, or 3) a curvilinear relationship. Second, these three adherence scenarios were evaluated in three personalized strategies. Our results show that it is more the absolute adherence rate than the nature of the risk-adherence relationship that is important to determine which strategy is the most cost-effective. Furthermore, probabilistic sensitivity analyses showed that there are risk-stratified screening strategies that are more cost-effective than routine screening if the willingness-to-pay threshold for screening is below US $60,000. CONCLUSIONS: Our results show that "nonadherence" affects the relative performance of screening strategies. Thus, it is necessary to include the true adherence level to evaluate personalized screening strategies and to select the best strategy.

Mammography Screening 2.0 - How Can Risk-Adapted Screening be Implemented in Clinical Practice?: Results of a Focus Group Discussion with Experts in the RISIKOLOTSE.DE Project.

INTRODUCTION: The mammography screening programme has been the subject of criticism for some time. Invitation to take part is currently based only on the risk factors of age and female sex, whereby women with an above-average risk are screened too seldom and women with a low risk are possibly screened too often. In future, an individualised risk assessment could make a risk-adapted procedure possible in breast cancer screening. In the RISIKOLOTSE.DE project, schemes are devised to calculate the individual breast cancer risk and evaluate the results. The aim is to assist doctors and screening participants in participatory decision-making. To gauge the baseline situation in the target groups, qualitative and quantitative surveys were conducted. METHOD: At the start of the project, a guideline-based focus group discussion was held with 15 doctors and representatives of the public health service. The transcript of this discussion was evaluated by means of a qualitative content analysis. RESULTS: The participants assessed the concept of risk-adapted screening positively overall. At the same time, the majority of them were of the opinion that the results of individualised risk calculation can be understood and evaluated adequately only by doctors. The great communication requirement and lack of remuneration were given as practical obstacles to implementation. DISCUSSION: The suggestions and new ideas from the focus group ranged from administrative and regulatory changes to new forms of counselling and adaptable practice aids. An important indicator for the RISIKOLOTSE.DE conception and for planning future surveys was that risk calculation for mammography screening 2.0 was regarded as a purely medical function and that the concept of participatory decision-making played hardly any part in the discussion.

The Association between Serum 25-Hydroxyvitamin D and Cancer Risk: Results from the Prospective KORA F4 Study.

BACKGROUND: Many studies have examined the relationship between vitamin D and specific types of cancer with inconsistent results. Furthermore, to date, no observational studies have demonstrated a clear relationship between vitamin D and total cancer risk. METHODS: We analyzed data from a population-based prospective cohort study including 2,003 initially cancer-free participants from the KORA F4 study with baseline serum 25-hydroxyvitamin D (25(OH)D) measurements (surveyed between 2006 and 2008). We used Cox proportional hazard models to assess the association between 25(OH)D levels and incident cancer risk. RESULTS: Within a follow-up period of 7 years, 69 of the participants developed cancer. Overall, we observed no significant relationship between serum 25(OH)D levels and cancer risk. The hazard ratio (HR) per 1 ng/ml increase in 25 (OH)D for this relationship was 1.00 (95% confidence interval (CI) 0.97-1.04) adjusting for age, sex, body mass index, and season of blood draw. This was also true in subgroup analysis for prostate cancer (HR 0.95, 95% CI 0.88-1.03), breast cancer (HR 1.03, 95% CI 0.97-1.09), and colorectal cancer (HR 0.97, 95% CI 0.88-1.07). CONCLUSION: Our study found no protective effect of 25(OH)D against developing cancer. However, studies with more participants and additional measurements of 25(OH)D are still needed to accurately clarify the relationship between 25(OH)D and total cancer risk.

Differential associations between diet and prediabetes or diabetes in the KORA FF4 study.

Type 2 diabetes mellitus (T2DM) is a global public health epidemic. Diet and lifestyle changes have been demonstrated as effective measures in managing T2DM and preventing or delaying the progression from prediabetes to diabetes, yet the relationship between diet, prediabetes and diabetes is still not entirely clear. The present study aimed to further elucidate the relationship between diet, diabetes and especially prediabetes. A total of 1542 participants of the cross-sectional, population-based Cooperative Health Research in the Region of Augsburg (KORA) FF4 study (2013/2014) were included in this analysis. Dietary intake was derived using a method combining information from a FFQ and repeated 24-h food lists. Glucose tolerance status was assessed via oral glucose tolerance tests in all participants without a previous physician-confirmed diagnosis of T2DM, and was classified according to the 2003 American Diabetes Association criteria. Crude and fully adjusted multinomial logistic regression models were fitted to examine associations between diet and prediabetes, undetected diabetes mellitus (UDM) and prevalent T2DM. After adjusting for major covariates, fruit was significantly inversely and total meat, processed meat, sugar-sweetened beverages and moderate alcohol significantly associated with UDM and/or prevalent diabetes. Sex-specific analyses showed that in men, coffee was significantly inversely (OR 0·80; 95 % CI 0·67, 0·96) and heavy alcohol significantly (OR 1·84; 95 % CI 1·14, 2·95) associated with prediabetes. Our findings on diet and T2DM are consistent with current literature, while our results regarding coffee, heavy alcohol consumption and prediabetes highlight new possible targets for primary prevention of the derangement of glucose homeostasis.