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Early recognition of hereditary urological cancers may influence diagnostic and therapeutic decision-making, and potentially alter the fate of patients and family members. Here, we introduce readers to the current knowledge on germline genetic testing and clinical practice in prostate, bladder, renal, and testicular carcinoma. Considering all urological cancer patients, routine inquiries about familial cancer history should become a standard practice in clinical settings. If suspicion arises, patients can opt for two avenues: referral to genetic counseling or undergoing genetic tests after consultation with the treating urologist. Patient summary: Tumors of the urogenital tract (prostate, kidney, bladder, and testes) can sometimes be related to genetic mutations that are present in all the cells of the body. Such mutations can be inherited and run in families. Therefore, it is relevant to obtain information on the incidence of all cancers in the family history. The information obtained may initiate genetic testing, leading to the identification of mutations that are related to cancer in the current or next generation. In addition, these mutations may offer alternative treatment options for patients.

Objective: To provide the most up-to-date data on the burden of malignant mesothelioma (MM) and the projections through 2029 in China. Methods: Data on patients diagnosed with MM from China during 1990–2019 were obtained from the Global Burden of Disease (GBD) 2019 database, including annual cases and deaths data and age-standardized rates of incidence, mortality, and disability-adjusted life-years (DALYs) associated with MM among different age groups. Temporal trends during 1990–2019 were analyzed by the Joinpoint regression models using 95% confidence interval (CI), while the projections through 2029 were calculated by the Bayesian age-period-cohort model. Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996–2023. Results: We observed a significant elevation in incident new cases and deaths over the last 3 decades, increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases. We found a roughly 6% increase in the proportion of incident cases for those aged >70 years (30% in 2019 versus 24% in 1990), while for the proportion of deaths similar elevation for those aged >70 years was found. Additionally, men had significantly higher DALYs due to MM across age groups compared with women. Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons. By 2029, the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both. Conclusion: We found, for the first time using GBD data on the Chinese population, that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade, suggesting an urgent need for a complete ban on chrysotile asbestos in China.

Abstract Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations. We identified 23 haplotypes that were associated with the risk of MGUS at the genome-wide significance level (p

Abstract Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of which are novel. Through functional fine-mapping and Mendelian randomization, we uncover two causal mechanisms for inherited MM risk: longer telomeres; and elevated levels of B-cell maturation antigen (BCMA) and interleukin-5 receptor alpha (IL5RA) in plasma. The largest increase in BCMA and IL5RA levels is mediated by the risk variant rs34562254-A at TNFRSF13B. While individuals with loss-of-function variants in TNFRSF13B develop B-cell immunodeficiency, rs34562254-A exerts a gain-of-function effect, increasing MM risk through amplified B-cell responses. Our results represent an analysis of genetic MM predisposition, highlighting causal mechanisms contributing to MM development.

Hepatocellular carcinoma (HCC) is primary liver cancer, frequently diagnosed at advanced stages with limited therapeutic options. MicroRNAs (miRNAs) regulate target gene expression and through inhibitory competitive binding of miRNA influence cellular processes including carcinogenesis. Extensive evidence proved that certain miRNA's are specifically expressed in neoplastic tissues of HCC patients and are confirmed as important factors that can participate in the regulation of key signalling pathways in cancer cells. As such, miRNAs have a great potential in the clinical diagnosis and treatment of HCC and can improve the limitations of standard diagnosis and treatment. Long non-coding RNAs (lncRNAs) have a critical role in the development and progression of HCC. HCC-related lncRNAs have been demonstrated to exhibit abnormal expression and contribute to transformation process (such as proliferation, apoptosis, accelerated vascular formation, and gain of invasive potential) through their interaction with DNA, RNA, or proteins. LncRNAs can bind mRNAs to release their target mRNA and enable its translation. These lncRNA-miRNA networks regulate cancer cell expression and so its proliferation, apoptosis, invasion, metastasis, angiogenesis, epithelial-mesenchymal transition (EMT), drug resistance, and autophagy. In this narrative review, we focus on miRNA and lncRNA in HCC tumor tissue and their interaction as current tools, and biomarkers and therapeutic targets unravelled in recent years.

Abstract Esophageal cancer (EC) and gastric cancer (GC) are fatal cancers with a relatively late age of onset. Age is a negative risk factor for survival in many cancers and our aim was to analyze age‐specific survival in EC and GC using the recently updated NORDCAN database. NORDCAN data originate from the Danish, Finnish, Norwegian, and Swedish nationwide cancer registries covering years 1972 through 2021 inviting for comparison of 50‐year survival trends between the countries. Relative 1‐ and 5‐year survival and 5/1‐year conditional survival (i.e., survival in those who were alive in Year 1 to survive additional 4 years) were analyzed. Survival in EC showed large gains for patients below age 80 years, 5‐year survival in Norwegian men reaching 30% and in women over 30% but for 80–89 year old survival remained at 10%. In contrast, hardly any gain was seen among the 80–89 year patients for 1‐year survival and small gains in 5 year and 5/1‐year survival. Survival gaps between age‐groups increased over time. For GC there was also a clear age‐related negative survival gradient but the survival gaps between the age groups did not widen over time; Norwegian male and female 5‐year survival for 80–89 year old was about 20%. The age‐specific survival difference in GC arose in Year 1 and did not essentially increase in 5‐year survival. While there were differences in survival improvements between the countries, poor survival of the 80–89 year old patients was shared by all of them. To conclude, survival has improved steadily in younger GC and EC patients in most Nordic countries. While the 80–89 year old population accounts for nearly a quarter of all patients and their poor survival depressed overall survival, which can therefore be increased further by improving diagnostics, treatment and care of elderly EC and GC patients.

Abstract Background The prognostic significance of mast cells and different phenotypes of macrophages in the microenvironment of hepatocellular carcinoma (HCC) following resection is unclear. We aimed in this study to assess the local distribution of infiltrating macrophages and mast cells of specific phenotypes in tissues of HCC and to evaluate their prognostic values for survival of post-surgical patients. Methods The clinicopathological and follow-up data of 70 patients with HCC, who underwent curative resection of tumor from 1997 to 2019, were collected. The infiltration of CD68+ and CD163+ macrophages and CD117+ mast cells was assessed immunohistochemically in representative resected specimens of HCC and adjacent tissues. The area fraction (AF) of positively stained cells was estimated automatically using QuPath image analysis software in several regions, such as tumor center (TC), inner margin (IM), outer margin (OM), and peritumor (PT) area. The prognostic significance of immune cells, individually and in associations, for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) was evaluated using Kaplan-Meier and Cox regression analyses. Results High AF of CD68+ macrophages in TC and IM and high AF of mast cells in IM and PT area were associated with a longer DFS. High AF of CD163+ macrophages in PT area correlated with a shorter DFS. Patients from CD163TChigh & CD68TClow group had a shorter DFS compared to all the rest of the groups, and cases with CD163IMlow & CD68IMhigh demonstrated significantly longer DFS compared to low AF of both markers. Patients from CD68IMhigh & CD163PTlow group, CD117IMhigh & CD163PTlow group, and CD117PThigh & CD163PTlow group had a significantly longer DFS compared to all other combinations of respective cells. Conclusions The individual prognostic impact of CD68+ and CD163+ macrophages and mast cells in the microenvironment of HCC after resection depends on their abundance and location, whereas the cumulative impact is built upon combination of different cell phenotypes within and between regions.

Abstract Backround We wanted to characterize conditional survival in prostate cancer (PC) in Sweden around and after 2005 when the vast increase in incidence due to the opportunistic testing for prostate specific antigen (PSA) culminated. We hypothesize that analyzing survival data during that time period may help interpret survival trends. We focus on stage‐specific analysis using conditional survival in order to define the periods when deaths most commonly occurred. Methods Data on PC patients were obtained from the Swedish cancer registry for analysis of 1‐, 2.5‐ and 5‐year relative survival and conditional relative survival between years 2004 and 2018. Tumor‐node‐metastatic stage classification at diagnosis was used to specify survival. Results Small improvements were observed in stage‐ and age‐related relative survival duriring the study period. Applying conditional relative survival showed that survival in stage T3 up to 2.5 years was better than survival between years 2.5 and 5. Survival in stage T4 was approximately equal in the first and the subsequent 2.5‐year period. For M1, the first 2.5 year survival period was worse than the subsequent one. The proportion of high risk and M1 disease in old patients (80+ years) remained very high and their survival improved only modestly. Conclusions The data indicate that M1 metastases kill more patients in the first 2.5 years than between years 2.5 and 5 after diagnosis; T4 deaths are equal in the two periods, and in T3 mortality in the first 2.5‐year period is lower than between years 2.5 and 5 after diagnosis. Conditional survival could be applied to explore critical survival periods even past 5 years after diagnoses and to monitor success in novel diagnostic and treatment practices. Improvement of survival in elderly patients may require clinical input.

Abstract Background Cancers of the head and neck (HN) are heterogeneous tumors with incidence rates varying globally. In Northern Europe oral and oropharyngeal cancers are the most common individual types. Survival for HN varies by individual tumor type but for most of them survival trends are not well known over extended periods of time. Methods Data for a retrospective survival study were obtained for Danish, Finnish, Norwegian, and Swedish patients from the NORDCAN database from 1971 to 2020. Relative 1‐ and 5‐year survival rates and 5/1‐year conditional survival for years 2–5 were calculated. Results Both 1‐ and 5‐year survival improved for all HN cancers but only marginally for laryngeal cancer. For the other cancers a 50‐year increase in 5‐year survival was about 30% units for nasopharyngeal and oropharyngeal cancers, 20% units for oral cancer and somewhat less for hypopharyngeal cancer. Conclusions 5‐year survival reached about 65% for all HN cancers, except for hypopharyngeal cancer (30%). Human papilloma virus infection is becoming a dominant risk factor for the rapidly increasing oropharyngeal cancer, the prevention of which needs to emphasize oral sex as a route of infection.