Global prostate cancer risk associated with microplastic exposure: a statistical and machine learning analysis

Germline genetic risk and prostate cancer-specific mortality in a population-based incident cohort.

BACKGROUND Multiple germline variants are associated with prostate cancer (PCa) susceptibility and aggressive features; however, their value for predicting prostate cancer-specific mortality (PCSM) at the time of diagnosis remains uncertain, particularly among men with clinically localized disease. METHODS We evaluated associations between germline risk factors and PCSM among 14,644 men with incident PCa in the UK Biobank. Associations between PCSM and reported germline risk factors, including 11 genes recommended by the National Comprehensive Cancer Network (NCCN), nine other candidate genes, two common variants [KLK3 (I179T) and HSD3B1 (1245 A > C)], and three polygenic risk scores (PRSs), were tested using Fine-Gray competing-risk models accounting for non-PCa mortality. RESULTS During a median follow-up of 6.73 years after diagnosis, 1581 men (10.8%) died from PCa. PVs in three NCCN-recommended DNA damage-repair genes (BRCA2, MSH6, PALB2) were individually associated with increased PCSM and were defined as Tier-1. Aggregated PVs in seven additional NCCN-recommended DDR genes (Tier-2) and the KLK3 I179T variant were also independently associated with PCSM. In contrast, HOXB13, nine other candidate genes, HSD3B1, and all three PRSs were not associated with cumulative PCSM risk. Overall, 14.45% of men carried Tier-1 or Tier-2 PVs and/or KLK3 I179T and experienced significantly earlier PCa-specific mortality. Importantly, associations remained significant among men without metastatic disease at diagnosis. CONCLUSIONS Reported inherited susceptibility to PCa does not uniformly confer risk of lethal progression. Germline PVs in NCCN-recommended DDR genes and the KLK3 I179T variant identify a subset of men at elevated risk of PCSM, including those with apparently localized disease. These findings support consideration of selected germline markers for prognostic risk stratification at diagnosis to inform individualized management decisions.

Clarifying risk-factor associations with quantitative breast tumor features: a pooled analysis of 24 studies.

Using big data for cancer prevention

Background/Context: Cancer, a very prevalent and deadly disease, is expected to increase significantly to approximately 35 million new cancer cases and 17 million deaths by 2050. There has been progress in cancer research; however, this progress applies to relatively few cancer types, and current approaches to epidemiological research are limiting. Problem Statement/Objective: Ninety to ninety-five percent of cancers are due to external exposures, but only 30–50 percent of all cancer cases can be prevented by reducing exposure to risk factors. Therefore, there is a lot to learn about the causal risk factors of cancers. Methods: Using secondary EHR data, we identified twelve cancer groupings that we consider poorly understood (5,950 cases, and 17,850 controls) and conducted case-control analyses to identify associations with selected clinical and environmental exposures. Results: Radiation exposure, hormone therapy, breast implants, orthopedic implants, and formaldehyde exposure were associated with increased odds in the incidence of poorly understood cancers. Conclusion/Implications: This research demonstrates the feasibility of using big data to conduct case-control analyses to identify associations between possible risk factors and cancers. This methodology is the first step to identify causal risk factors between cancers and exposures. It can quickly provide guidance on which factors seem to have an association, and which do not. This can increase the rate at which the causal risk factors of cancers are identified and lead to an equitable reduction in the number of expected cancer cases and deaths. This methodology can be replicated with varying cancer types and exposures and enables research on rare conditions that was not possible due to small numbers. This methodology also overcomes the limitations of the traditional epidemiological approach by requiring less effort, time, and cost. The use of secondary data for research can produce results at a faster rate while incurring less cost and effort.

Real-World Evidence for Breast Cancer Risk Stratification: Insights from the P.I.N.K. Study

Simple Summary Early detection of breast cancer greatly improves outcomes, with the 5-year survival rate reaching 99% when the disease is found at an early stage. One promising approach to improve early detection is risk-based breast screening, which tailors screening recommendations according to a woman’s individual risk factors, including medical history, personal characteristics, and lifestyle habits. The Prevention, Imaging, Network, Knowledge (P.I.N.K.) study was created to collect real-world data from a large group of women across Italy and to support the development of more personalized breast cancer screening strategies. By combining information gathered during routine breast clinic visits with answers provided by women through a structured questionnaire, we examined factors associated with the development of breast cancer. Our findings identified several personal characteristics that were more strongly linked to breast cancer occurrence, highlighting the value of integrating clinical and self-reported information to better understand individual risk and support more targeted prevention and screening efforts. By providing additional evidence on the contribution of potentially modifiable risk factors, this study helps identify priorities for future research aimed at improving breast cancer risk stratification, informing the development of more targeted screening strategies, and facilitating discussions with women about the impact of lifestyle on breast cancer risk.

Cardiovascular disease in breast cancer patients receiving chemotherapy: epidemiology and risk factors

Breast cancer is the most common malignancy among women worldwide, and chemotherapy remains a cornerstone of its treatment. However, chemotherapy can increase the risk of cardiovascular disease (CVD), which is a major cause of morbidity and mortality in cancer survivors. Understanding the prevalence and risk factors for CVD in this population is essential for improving long-term outcomes. This study aimed to evaluate the occurrence of new-onset CVD in women with breast cancer undergoing chemotherapy and to identify factors associated with increased risk. We conducted a retrospective cohort study using administrative data from a Slovak health insurance company covering 1.77 million insurees (2024). We included women with breast cancer (ICD-10: C50*) who initiated chemotherapy (ATC groups L01 or L02) between 2013 and 2024. Baseline CVD status was assessed using administrative records from the two years prior to chemotherapy initiation. New-onset CVD was ascertained from the date of treatment initiation and followed for a mean of 3.8 years (SD 3.4). To identify factors associated with incident CVD, we applied multivariate Cox proportional hazards regression in the subset of patients without prior CVD. 10,171 women with mean age of 60.2 (SD 12.6) started chemotherapy treatment for breast cancer between years 2013 and 2024. 62.8% of them had no CVD present at the start of treatment (except for hypertension), with mean age of 55.8 (SD 11.4). Share of patients with CVD increased to 49.1% at 1 year and 63.3% at 5 years after treatment initiation. In CVD-naive patients, ischaemic heart disease was the most common CVD, with 13.0% of patients developing it within 5 years, followed by arrythmia (10.5%), atherosclerosis (8.3%), embolism and thrombosis (7.8%) and heart failure (4.7%). In patients with established CVD, the prevalence of individual diagnoses shows around two-fold increase within 5 years (Table 1). Model showed that higher age (40–64 years: HR = 1.38, ≥65 years: HR = 2.13), presence of hypertension (HR = 1.69), diabetes (HR = 1.18), chronic kidney failure (HR = 1.60) and longer chemotherapy episodes (1–4 years: HR = 1.12, ≥4 years: HR = 1.18) were significantly associated with higher CVD risk, while initial chemotherapy of L02 class was associated with lower risk (HR = 0.75). Cardiovascular disease represents a substantial and increasing burden among women undergoing chemotherapy for breast cancer. A large proportion of initially CVD-naive patients developed cardiovascular conditions over follow-up. Among incident diagnoses, ischaemic heart disease had the highest 5-year cumulative incidence, followed by arrhythmias, thromboembolic events, and atherosclerotic disease. Together with the approximately two-fold higher prevalence observed in patients with preexisting CVD, this study highlights the need for sustained cardiovascular surveillance in breast cancer survivors.Table 1Prevalence of selected CVD

SMOKING, ENVIRONMENTAL EXPOSURES, AND CHRONIC LUNG DISEASE AS KEY RISK FACTORS FOR LUNG CANCER IN NORTH SUMATRA.

BACKGROUND Lung cancer remains the leading cause of cancer mortality worldwide, with increasing incidence in many developing countries. Understanding region-specific risk factors is essential for effective prevention strategies. This study aimed to identify major determinants of lung cancer in North Sumatra, Indonesia. MATERIALS AND METHODS A hospital-based observational study with a case-control analytical approach was conducted between August and November 2024 in three referral hospitals in North Sumatra. A total of 240 patients with histologically confirmed lung cancer and 240 controls without malignancy or chronic respiratory disease were included. Participants were comparable by sex and residential area, while age differences between groups were statistically adjusted in the multivariate regression model. RESULTS Smoking exposure differed significantly between cases and controls (p = 0.023). The multivariate analysis identified several independent predictors of lung cancer. Age <45 years increased the risk more than two-fold (OR 2.62; 95% CI 1.10-6.21), whereas age >65 years showed a lower relative risk (OR 0.54; 95% CI 0.33-0.88). The occupational exposure signicantly increased lung cancer risk (OR 1.91; 95% CI 1.13-3.25). Unhealthy indoor environments, characterized by poor ventilation and household pollutant exposure, were also associated with an increased risk (OR 2.53; 95% CI 1.45-4.40). Chronic respiratory diseases, particularly tuberculosis and chronic obstructive pulmonary disease, were more prevalent among cases and contributed to the elevated risk. CONCLUSIONS Smoking exposure, occupational hazards, unhealthy indoor environments, and chronic pulmonary diseases are important determinants of lung cancer in North Sumatra. Public health strategies focusing on tobacco control, improved workplace safety, and reduction of indoor air pollution may substantially reduce lung cancer burden in this region.