Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

Incidence and survival of patients with malignant pancreatic neuroendocrine neoplasms in Germany, 2009-2021.

BACKGROUND: Due to the rarity of pancreatic neuroendocrine neoplasms, only few population-representative studies on incidence and survival have been conducted. The aim was to provide up-to-date nationwide incidence and relative survival estimates of neuroendocrine (NE) neoplasms overall, NE tumors (NETs), NE carcinomas (NECs), and mixed NE neoplasms (MiNEN). METHODS: We distinguished between pancreatic NETs (functioning versus non-functioning), NECs and mixed NE neoplasms and analyzed data from 2009 through 2021 from all German cancer registries covering a population of more than 80 million. We calculated crude and age-standardized incidence rates and 5-year relative survival estimates (RS). RESULTS: Overall 6474, 4217, and 243 patients with pancreatic NETs, NECs, and mixed NE neoplasms, respectively were registered. While the age-standardized incidence of NETs has increased (+16.4 % per year, 95 %CI 12.2;20.7), the incidence of NEC has fallen (about -6.4 % per year, 95 %CI -8.0; -4.8). The crude RS was 77.7 % (standard error [SE] 0.9) for non-functioning NETs, 90.3 % for functioning NETs (SE 3.9), and 18.5 % (SE 3.9) for MiNEN. Large and small cell NECs had a low RS (9.1 % and 6.9 %, respectively). RS for G1 NETs was 88.2 %, while it was only 36.6 % for G3 NETs. Localized NETs had a RS of 92.8 %, while distant metastatic NETs had a RS of 45.0 %. CONCLUSIONS: The incidence of pancreatic NETs has increased markedly in Germany in the period 2009-2021. Subgroups of NETs (G1 grading or localized stage) have an excellent prognosis. RS of MiNEN is more similar to NECs than NETs.

Survival analysis for lung cancer patients: A comparison of Cox regression and machine learning models.

INTRODUCTION: Survival analysis based on cancer registry data is of paramount importance for monitoring the effectiveness of health care. As new methods arise, the compendium of statistical tools applicable to cancer registry data grows. In recent years, machine learning approaches for survival analysis were developed. The aim of this study is to compare the model performance of the well established Cox regression and novel machine learning approaches on a previously unused dataset. MATERIAL AND METHODS: The study is based on lung cancer data from the Schleswig-Holstein Cancer Registry. Four survival analysis models are compared: Cox Proportional Hazard Regression (CoxPH) as the most commonly used statistical model, as well as Random Survival Forests (RSF) and two neural network architectures based on the DeepSurv and TabNet approaches. The models are evaluated using the concordance index (C-I), the Brier score and the AUC-ROC score. In addition, to gain more insight in the decision process of the models, we identified the features that have an higher impact on patient survival using permutation feature importance scores and SHAP values. RESULTS: Using a dataset including the cancer stage established by the Union for International Cancer Control (UICC), the best performing model is the CoxPH (C-I: 0.698±0.005), while using a dataset which includes the tumor size, lymph node and metastasis status (TNM) leads to the RSF as best performing model (C-I: 0.703±0.004). The explainability metrics show that the models rely on the combined UICC stage and the metastasis status in the first place, which corresponds to other studies. DISCUSSION: The studied methods are highly relevant for epidemiological researchers to create more accurate survival models, which can help physicians make informed decisions about appropriate therapies and management of patients with lung cancer, ultimately improving survival and quality of life.

Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk.

Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10-5). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.

Cancer-specific risk prediction with a serum microRNA signature.

We recently derived and validated a serum-based microRNA risk score (miR-score) that predicted colorectal cancer (CRC) occurrence with very high accuracy within 14 years of follow-up in a population-based cohort study from Germany (ESTHER cohort). Here, we aimed to evaluate associations of the CRC-specific miR-score with the risk of developing other common cancers, including female breast cancer (BC), lung cancer (LC), and prostate cancer (PC), in the ESTHER cohort. MicroRNAs (miRNAs) were profiled by quantitative real-time PCR in serum samples collected at baseline from randomly selected incident cases of BC (n = 90), LC (n = 88), and PC (n = 93) and participants without diagnosis of CRC, LC, BC, or PC (controls, n = 181) until the end of the 17-year follow-up. Multivariate logistic regression models were used to evaluate the associations of the miR-score with BC, LC, and PC incidence. The miR-score showed strong inverse associations with BC and LC incidence [odds ratio per 1 standard deviation increase: 0.60 (95% confidence interval [CI] 0.43-0.82), p = 0.0017, and 0.64 (95% CI 0.48-0.84),p = 0.0015, respectively]. Associations with PC were not statistically significant but pointed in the positive direction. Our study highlights the potential of serum-based miRNA biomarkers for cancer-specific risk prediction. Further large cohort studies aiming to investigate, validate, and optimize the use of circulating miRNA signatures for cancer risk assessment are warranted.

Personality and the use of cancer screenings - Results of the German National Cohort.

Objective: To determine the association between personality characteristics and use of different cancer screenings. Methods: We used data from the German National Cohort (NAKO; mean age was 53.0 years (SD: 9.2 years)) - a population-based cohort study. A total of 132,298 individuals were included in the analyses. As outcome measures, we used (self-reported): stool examination for blood (haemoccult test, early detection of bowel cancer), colonoscopy (screening for colorectal cancer), skin examination for moles (early detection of skin cancer), breast palpation by a doctor (early detection of breast cancer), x-ray examination of the breast ("mammography", early detection of breast cancer), cervical smear test, finger examination of the rectum (early detection of prostate cancer), and blood test for prostate cancer (determination of Prostate-Specific Antigen level). The established Big Five Inventory-SOEP was used to quantify personality factors. It was adjusted for several covariates based on the Andersen model. Unadjusted and adjusted multiple logistic regressions were computed. Results: A higher probability of having a skin examination for moles, for example, was associated with a higher conscientiousness (OR: 1.07, p < 0.001), higher extraversion (OR: 1.03, p < 0.001), higher agreeableness (OR: 1.02, p < 0.001), lower openness to experience (OR: 0.98, p < 0.001) and higher neuroticism (OR: 1.07, p < 0.001) among the total sample. Depending on the outcome used, the associations slightly varied. Conclusions: Particularly higher levels of extraversion, neuroticism and conscientiousness are associated with the use of different cancer screenings. Such knowledge may help to better understand non-participation in cancer screening examinations from a psychological perspective.

Strong associations of serum selenoprotein P with all-cause mortality and mortality due to cancer, cardiovascular, respiratory and gastrointestinal diseases in older German adults.

BACKGROUND: Selenium is an essential trace mineral. The main function of selenoprotein P (SELENOP) is to transport selenium but it has also been ascribed anti-oxidative effects. METHODS: To assess the association of repeated measurements of serum SELENOP concentration with all-cause and cause-specific mortality serum SELENOP was measured at baseline and 5-year follow-up in 7,186 and 4,164 participants of the ESTHER study, a German population-based cohort aged 50-74 years at baseline. RESULTS: During 17.3 years of follow-up, 2,126 study participants (30%) died. The relationship of serum SELENOP concentration with all-cause mortality was L-shaped, with mortality being significantly higher at SELENOP concentrations < 4.1 mg/L, which is near the bottom tertile's cut-off (4.2 mg/L). All-cause mortality of participants in the bottom SELENOP tertile was significantly increased compared to subjects in the top tertile (hazard ratio [95% confidence interval]: 1.35 [1.21-1.50]). SELENOP in the bottom tertile was further associated with increased cardiovascular mortality (1.24 [1.04-1.49]), cancer mortality (1.31 [1.09-1.58]), respiratory disease mortality (2.06 [1.28-3.32]) and gastrointestinal disease mortality (2.04 [1.25-3.32]). The excess risk of all-cause mortality for those in the bottom SELENOP tertile was more than twice as strong in men as in women (interaction of SELENOP and sex; p = 0.008). CONCLUSIONS: In this large cohort study, serum SELENOP concentration was inversely associated with all-cause and cause-specific mortality. Consistent inverse associations with multiple mortality outcomes might be explained by an impaired selenium transport and selenium deficiency in multiple organs. Trials testing the efficacy of selenium supplements in subjects with low baseline SELENOP concentration are needed. TRIAL REGISTRATION: Retrospectively registered in the German Clinical Trials Register on Feb 14, 2018 (ID: DRKS00014028).

Childhood Trauma and Somatic and Mental Illness in Adulthood.

BACKGROUND: Childhood trauma is associated with somatic and mental illness in adulthood. The strength of the association varies as a function of age, sex, and type of trauma. Pertinent studies to date have mainly focused on individual diseases. In this study, we investigate the association between childhood trauma and a multiplicity of somatic and mental illnesses in adulthood. METHODS: Data from 156 807 NAKO Health Study participants were analyzed by means of logistic regressions, with adjustment for age, sex, years of education, and study site. The Childhood Trauma Screener differentiated between no/minor (n = 115 891) and moderate/severe childhood trauma (n = 40 916). The outcome variables were medical diagnoses of five somatic and two mental health conditions as stated in the clinical history. RESULTS: Persons with childhood trauma were more likely to bear a diagnosis of all of the studied conditions: cancer (odds ratio [OR] = 1.10; 95% confidence interval: [1.05; 1.15]), myocardial infarction (OR = 1.13 [1.03; 1.24]), diabetes (OR = 1.16, [1.10; 1.23]), stroke (OR = 1.35 [1.23; 1.48]), chronic obstructive pulmonary disease (OR = 1.45 [1.38; 1.52]), depression (OR = 2.36 [2.29; 2.43]), and anxiety disorders (OR = 2.08 [2.00; 2.17]). All of these associations were stronger in younger persons, regardless of the nature of childhood trauma. Differences between the sexes were observed only for some of these associations. CONCLUSION: Childhood trauma was associated with a higher probability of developing mental as well as somatic illness in adulthood. As childhood trauma is an element of individual history that the victim has little to no control over, and because the illnesses that can arise in adulthood in association with it are a heavy burden on the affected persons and on society, there is a need for research on these associations and for the development of preventive measures.

Diabetes mellitus in long-term survivors with colorectal, breast, or prostate cancer: Prevalence and prognosis. A population-based study.

BACKGROUND: Patients with cancer are at increased risk of diabetes mellitus (DM). Previous studies on the prevalence and prognostic impact of DM in cancer survivors were limited by small sample sizes or short follow-up times. We aimed to compare the patient-reported prevalence of DM in long-term cancer survivors (LTCS), who survived 5 years or more after cancer diagnosis, with that in cancer-free controls, and to estimate the mortality risk among LTCS according to DM status. METHODS: Our population-based cohort comprised 6952 LTCS diagnosed with breast, colorectal, or prostate cancer between 1994 and 2004, recruited in 2008-2011 (baseline), and followed until 2019. A total of 1828 cancer-free individuals served as controls. Multivariable logistic regression was used to compare the prevalence of DM in LTCS and controls, and according to covariates at baseline. Mortality among LTCS according to DM was assessed by Cox proportional hazards regression. RESULTS: A total of 962 (13.8%) LTCS at baseline reported DM. Prevalence of DM in LTCS was not higher than in cancer-free controls, both at baseline (odds ratio, 0.80; 95% CI, 0.66-0.97) and at follow-up (odds ratio, 0.83; 95% CI, 0.67-1.04). Prevalence of DM in LTCS was associated with cancer site, older age, lower education, higher socioeconomic deprivation, higher body mass index, physical inactivity, other comorbidities, and poorer prognosis (adjusted hazard ratio [all-cause mortality] = 1.29; 95% CI, 1.15-1.44). CONCLUSION: DM in LTCS is prevalent, but not higher than in cancer-free population controls. Cancer survivors with concurrent DM are at a potentially higher risk of death. PLAIN LANGUAGE SUMMARY: Cancer and diabetes mellitus (DM) are two serious threats to global health. In our study, prevalence of DM in long-term cancer survivors who survived 5 years or more after cancer diagnosis was not higher than in cancer-free controls. This should not be interpreted as an indication of a lower risk of DM in cancer survivors. Rather, it highlights the potentially poor prognosis in diabetic cancer survivors. Therefore, keeping a continuous satisfactory DM and hyperglycemia management is essential during long-term cancer survivorship.

Does breast cancer modify the long-term relationship between lifestyle behaviors and mortality? A prospective analysis of breast cancer survivors and population-based controls.

BACKGROUND: Modifiable lifestyle factors are known to impact survival. It is less clear whether this differs between postmenopausal women ever diagnosed with breast cancer and unaffected women. METHODS: Women diagnosed with breast cancer and unaffected women of comparable age were recruited from 2002 to 2005 and followed up until 2020. Using baseline information, a lifestyle adherence score (range 0-8; categorized as low [0-3.74], moderate [3.75-4.74], and high [≥4.75]) was created based on the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. Cox regression and competing risks analysis were used to analyze the association of adherence to WCRF/AICR lifestyle recommendations with overall mortality and with death due to cardiovascular diseases and cancer, respectively. RESULTS: A total of 8584 women were included (2785 with breast cancer and 5799 without). With a median follow-up of 16.1 years there were 2006 total deaths. Among the deaths of known causes (98.6%), 445 were cardiovascular-related and 1004 were cancer-related. The average lifestyle score was 4.2. There was no differential effect of lifestyle score by case-control status on mortality. After adjusting for covariates, moderate (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.57-0.76) and high (HR, 0.54; 95% CI, 0.47-0.63) adherence to WCRF/AICR lifestyle recommendations were significantly associated with a decrease in overall mortality. Similarly, in competing risks analysis, moderate and high adherence were associated with decreased mortality from cardiovascular diseases and from cancer. CONCLUSIONS: A healthy lifestyle can substantially reduce mortality risk in women. With low adherence to all WCRF/AICR guidelines in about a third of study participants, health interventions are warranted.

Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer.

Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a large-scale molecular epidemiology approach to shed light on the putative role of melatonin in breast cancer. We investigated associations between breast-cancer risk and polymorphisms at genes of melatonin biosynthesis/signaling using a study population of 44,405 women from the Breast Cancer Association Consortium (22,992 cases, 21,413 population-based controls). Genotype data of 97 candidate single nucleotide polymorphisms (SNPs) at 18 defined gene regions were investigated for breast-cancer risk effects. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) by logistic regression for the main-effect analysis as well as stratified analyses by estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP interactions were analyzed via a two-step procedure based on logic regression. The Bayesian false-discovery probability (BFDP) was used for all analyses to account for multiple testing. Noteworthy associations (BFDP < 0.8) included 10 linked SNPs in tryptophan hydroxylase 2 (TPH2) (e.g. rs1386492: OR = 1.07, 95% CI 1.02-1.12), and a SNP in the mitogen-activated protein kinase 8 (MAPK8) (rs10857561: OR = 1.11, 95% CI 1.04-1.18). The SNP-SNP interaction analysis revealed noteworthy interaction terms with TPH2- and MAPK-related SNPs (e.g. rs1386483R ∧ rs1473473D ∧ rs3729931D: OR = 1.20, 95% CI 1.09-1.32). In line with the light-at-night hypothesis that links shift work with elevated breast-cancer risks our results point to SNPs in TPH2 and MAPK-genes that may impact the intricate network of circadian regulation.

A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma.

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P = 2.46 × 10-9), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P = 1.53 × 10-6). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting reanalysis of genome-wide association studies (GWASs) in light of functional data.

Population-Based Clinical Cancer Registration in Germany.

INTRODUCTION: In 2013, a new federal law obligated all German federal states to collect additional clinical data in population-based cancer registries as an active tool for monitoring and improving the quality of cancer care, increasing transparency and promoting health research. Now, 10 years later, the current status of the expanded cancer registration is presented, including current figures on cancer in Germany. METHODS: Reporting of cancer is mandatory for physicians, and about 5 to 10 reports from different healthcare providers are expected for each case. A uniform national dataset of about 130 items is used, and reports are usually sent electronically to the registry. We used the most recent data available from cancer registries up to the year of diagnosis in 2019. We calculated incidence rates and 5-year relative survival (5YRS) for common cancers. Data on clinical outcomes and benchmarking based on quality indicators (QIs) from guidelines were provided by the Cancer Registry Schleswig-Holstein (CR SH). RESULTS: All federal state cancer registries met most of the previously defined national eligibility criteria. Approximately 505,000 cancer cases were registered in 2019, with breast, prostate, colorectal and lung cancer being the most common cancers. The age-standardised cancer incidence has slightly decreased during the last decade. and spatial heterogeneity can be observed within Germany. 5YRS for all cancers was 67% and 63% for women and men, respectively. Therapy data for rectal cancer in 2019-2021 from the CR SH are shown as an example: 69% of the registered patients underwent surgery, mostly with curative intent (84%) and tumour-free resection (91%). Radiotherapy was given to 33% of the patients, and chemotherapy was given to 40%. Three selected QIs showed differences between involved healthcare providers. DISCUSSION: The implementation of population-based clinical cancer registration can be considered a success. Comprehensive recording of diagnosis, treatment and disease progression and the use of registry data for quality assurance, benchmarking and feedback have been implemented.

Trends in cancer incidence by socioeconomic deprivation in Germany in 2007 to 2018: An ecological registry-based study.

Age-standardized cancer incidence has decreased over the last years for many cancer sites in developed countries. Whether these trends led to narrowing or widening socioeconomic inequalities in cancer incidence is unknown. Using cancer registry data covering 48 million inhabitants in Germany, the ecological association between age-standardized total and site specific (colorectal, lung, prostate and breast) cancer incidence in 2007 to 2018 and a deprivation index on district level (aggregated to quintiles) was investigated. Incidence in the most and least deprived districts were compared using Poisson models. Average annual percentage changes (AAPCs) and differences in AAPCs between deprivation quintiles were assessed using Joinpoint regression analyses. Age-standardized incidence decreased strongly between 2007 and 2018 for total cancer and all cancer sites (except female lung cancer), irrespective of the level of deprivation. However, differences in the magnitude of trends across deprivation quintiles resulted in increasing inequalities over time for total cancer, colorectal and lung cancer. For total cancer, the incidence rate ratio between the most and least deprived quintile increased from 1.07 (95% confidence interval: 1.01-1.12) to 1.23 (1.12-1.32) in men and from 1.07 (1.01-1.13) to 1.20 (1.14-1.26) in women. Largest inequalities were observed for lung cancer with 82% (men) and 88% (women) higher incidence in the most vs the least deprived regions in 2018. The observed increase in inequalities in cancer incidence is in alignment with trends in inequalities in risk factor prevalence and partly utilization of screening. Intervention programs targeted at socioeconomically deprived and urban regions are highly needed.

Benefit finding, posttraumatic growth and health-related quality of life in long-term cancer survivors: a prospective population-based study.

BACKGROUND: We explored the relationship between benefit finding (BF)/posttraumatic growth (PTG) at baseline and health-related quality of life (HRQOL) at baseline and follow-up in long-term cancer survivors (LTCS; ≥5-year post-diagnosis). MATERIALS AND METHODS: HRQOL was assessed in LTCS in 2009-2011 (5- to 16-year post-diagnosis, baseline) and re-assessed in 2018/2019 (14- to 24-year post-diagnosis, follow-up). BF and PTG were measured at baseline; mean scores were dichotomized into 'none-to-low' (<3) and 'moderate-to-high' (> =3). Linear regression models and linear mixed regression models were employed to assess the association of BF/PTG with HRQOL. RESULTS: Of the 6057 baseline participants, 4373 were alive in 2019, of whom 2704 completed the follow-up questionnaire. Cross-sectionally, LTCS with none-to-low BF reported better HRQOL at baseline and at follow-up than LTCS with higher BF. Longitudinally, no difference was found between none-to-low and moderate-to-high BF on the HRQOL change from baseline to follow-up. HRQOL differences between the PTG groups were not statistically significant cross-sectionally and longitudinally, except those participants with moderate-to-high PTG reported higher role functioning and global health status/QOL. CONCLUSIONS: Cross-sectionally, BF was significantly negatively related to subscales of HRQOL, while PTG was positively correlated to role functioning and global health status/QOL. The results add further evidence that BF and PTG are two different positive psychological concepts.

The impact of cardiovascular disease on all-cause and cancer mortality: results from a 16-year follow-up of a German breast cancer case-control study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. The aim of this study was to examine if CVD affects the mortality of women after a breast cancer diagnosis and population controls differently. METHODS: The analysis included a total of 3,555 women, diagnosed with primary stage 1-3 breast cancer or in situ carcinoma between 2002 and 2005 and 7,334 controls breast cancer-free at recruitment, all aged 50-74 years, who were followed-up in a German breast cancer case-control study until June, 30 2020. Kaplan-Meier and cumulative incidence function were calculated for all-cause mortality and mortality from any cancer, stratified for case-control status and CVD, separately for women aged < 65 and ≥ 65 years. Cox regression and Fine-Gray subdistribution hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between case-control-status, CVD and mortality from all causes/any cancer. RESULTS: The median follow-up was 16.1 years. In total, 1,172 cases (33.0%) and 1,401 initial controls (19.1%) died. CVD prevalence at recruitment was 15.2% in cases and controls. Cases with CVD had the highest and controls without CVD the lowest mortality during the entire observation period in both age groups (< 65 and ≥ 65 years). CVD was identified as a risk factor for all-cause mortality in both cases and controls aged < 65 years (HR 1.22, 95%CI 0.96-1.55 and HR 1.79, 95%CI 1.43-2.24) as well as at ages of ≥ 65 years (HR 1.44, 95%CI 1.20-1.73 and HR 1.59, 95%CI 1.37-1.83). A significant association of CVD and cancer mortality was found only for cases aged ≥ 65 years. CONCLUSION: CVD was significantly associated with all-cause mortality of both cases and controls and CVD was identified as a risk factor for cancer mortality of cases aged ≥ 65 years at recruitment. Therefore, attention should be paid on monitoring and preventing CVD in breast cancer patients, especially in those diagnosed at older ages.

Persisting Deficits in Health-Related Quality of Life of Colorectal Cancer Survivors 14-24 Years Post-Diagnosis: A Population-Based Study.

(1) Background: The health-related quality of life (HRQOL) of colorectal cancer (CRC) survivors >10 years post-diagnosis is understudied. We aimed to compare the HRQOL of CRC survivors 14-24 years post-diagnosis to that of age- and sex-matched non-cancer controls, stratified by demographic and clinical factors. (2) Methods: We used data from 506 long-term CRC survivors and 1489 controls recruited from German population-based multi-regional studies. HRQOL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Core-30 (EORTC QLQ-C30) questionnaire. We estimated differences in the HRQOL of CRC survivors and controls with multiple regression, adjusted for age at survey, sex, and education, where appropriate. (3) Results: CRC survivors reported poorer social functioning but better health status/QOL than controls. CRC survivors, in general, had higher levels of symptom burden, and in particular diarrhea and constipation, regardless of demographic or clinical factors. In stratified analyses, HRQOL differed by age, sex, cancer type, and having a permanent stoma. (4) Conclusions: Although CRC survivors may have a comparable health status/QOL to controls 14-24 years after diagnosis, they still live with persistent bowel dysfunction that can negatively impact aspects of functioning. Healthcare providers should provide timely and adapted follow-up care to ameliorate potential long-term suffering.

Incidence, mortality and trends of cutaneous squamous cell carcinoma in Germany, the Netherlands, and Scotland.

AIM OF THE STUDY: Cutaneous squamous cell carcinoma (cSCC) incidences are increasing but scarcely available separated. We analysed incidence rates of cSCC over three decades with an extrapolation to 2040. METHODS: Cancer registries from the Netherlands, Scotland and two federal states of Germany (Saarland/Schleswig-Holstein) were sourced for separate cSCC incidence data. Incidence and mortality trends between 1989/90 and 2020 were assessed using Joinpoint regression models. Modified age-period-cohort models were applied to predict incidence rates up to 2044. Rates were age-standardised using the new European standard population (2013). RESULTS: Age-standardised incidence rates (ASIR, per 100,000 persons per year) increased in all populations. The annual percent increase ranged between 2.4% and 5.7%. The highest increase occurred in the age groups ≥60 years, especially in men aged ≥80 years, with a three to 5-fold increase. Extrapolations up to 2044 showed an unrestrained increase in incidence rates in all countries investigated. Age-standardised mortality rates (ASMR) showed slight increases between 1.4 and 3.2% per year in Saarland and Schleswig-Holstein for both sexes and for men in Scotland. For the Netherlands, ASMRs remained stable for women but declined for men. CONCLUSION: There was a continuous increase of cSCC incidence over three decades with no tendency for levelling-off, especially in the older populations as males ≥80 years. Extrapolations point to a further increasing number of cSCC up to 2044, especially among ≥60 years. This will have a significant impact on the current and future burden on dermatologic health care which will be faced with major challenges.