Search Results (1,151)

Background: MicroRNAs (miRNAs) such as miR-155-5p and miR-221-3p are key regulators of gene expression in cancer. Although both have been implicated in colorectal cancer (CRC) and papillary thyroid carcinoma (PTC), data on their regional expression profiles and clinical associations remain scarce, particularly in the Middle East. This study assessed the expression patterns and clinical relevance of miR-155-5p and miR-221-3p in CRC and PTC patients from Sulaymaniyah Province, Iraq. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor and adjacent normal tissue samples were collected from 60 CRC patients and 50 PTC patients. miRNA expression levels were quantified using real-time quantitative PCR (RT-qPCR) and analyzed by the ΔΔCt method, adjusted for tumor cellularity. Statistical analyses were conducted to evaluate associations between miRNA expression and clinicopathological parameters. Results: miR-155-5p and miR-221-3p were frequently overexpressed in both CRC (65%) and PTC (72% and 68%, respectively). In CRC, miR-155-5p expression correlated significantly with histological grade, tumor location, and TNM stage (p < 0.05), while miR-221-3p did not show significant associations with clinicopathological features. In PTC, miR-155-5p exhibited a trend toward association with TNM stage (p = 0.02). No significant differences in expression levels of these miRNAs were observed between CRC and PTC samples. Conclusions: Overall, miR-155-5p and miR-221-3p are consistently overexpressed in CRC and PTC, indicating their potential as diagnostic biomarkers. miR-155-5p, in particular, shows promise as a marker of disease progression in CRC. These findings underscore the importance of region-specific studies in advancing our understanding of the molecular landscape of cancer. Full article

Background: Mantle Cell Lymphoma (MCL) is an aggressive malignancy with variable clinical behavior, largely reflecting the underlying molecular heterogeneity. The genomic landscape of MCL encompasses gene mutations with strong prognostic implications and secondary genetic events, which are also implicated in the pathogenesis and prognosis of the disease. Methods: We evaluated the diagnostic samples of 73 patients with relapsed/refractory MCL that were enrolled in the Fondazione Italiana Linfomi Mantle First-BIO study. All patients had available data for correlating CNVs with the presence of TP53 mutation. Time to first relapse or progression of disease (POD) was used as the primary outcome measure. Results: We identified CNVs associated with MCL, with Del 9p21.3 (CDKN2A) being the strongest predictor of shorter time to POD (p = 0.01), independently of TP53 mutation in multivariable analysis. Unsupervised clustering identified molecularly defined clusters that were associated with significantly different times to POD (p = 0.01). Pairwise log-rank tests confirmed TP53 mutated vs. wild-type (WT) as the strongest prognostic factor, with cluster assessment improving the prognostic predictivity among patients: clusters TP53-mut vs. TP53-WT, p = 0.001, HR = 3.92; and p = 0.014, HR = 2.23, respectively. In conclusion, CNV-based molecular clusters might represent a novel approach to identify patients at higher risk of treatment failure, further contributing to the prognostic predictivity of TP53 mutation. Full article

Background: Muscle-invasive bladder cancer (MIBC) represents a highly aggressive malignancy associated with significant morbidity and mortality. The current standard treatment, which includes radical cystectomy and platinum-based chemotherapy, is burdened by high toxicity and a substantial risk of relapse. For this reason, over the past decade, novel therapeutic strategies involving immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), and targeted therapies have been investigated. This review aims to summarize current clinical evidence and ongoing trials evaluating these approaches in the perioperative setting. Methods: A systematic search was conducted using PubMed, EMBASE, and Cochrane databases, along with abstracts from major oncology conferences (ASCO, ESMO, SGO). Clinical trials assessing ICIs, ADCs, and targeted therapies, either alone or in combination with each other or with chemotherapy, in MIBC, were included. Results: Several early-phase and phase III trials have investigated the perioperative management of MIBC. Various studies evaluated the addition of ICIs to standard chemotherapy, demonstrating promising results in terms of pathological complete response. In parallel, the encouraging outcomes with ICIs and ADCs alone in the neoadjuvant or adjuvant setting paved the way for their combination in integrated strategies. Biomarker-driven approaches, based on circulating tumor DNA and specific genomic alterations, are being actively explored to improve patient selection and personalize treatment. Conclusions: ICIs, ADCs, and targeted therapies are reshaping the therapeutic landscape of MIBC. While early results are promising, further data and biomarker validation are essential to establish their definitive role and guide clinical decision-making in the perioperative setting. Full article

Background/Objectives: PPP2R1A encodes the scaffold subunit Aα of protein phosphatase 2A (PP2A). Pathogenic variants cause Houge-Janssens syndrome 2, a rare neurodevelopmental disorder characterized by developmental delay, intellectual disability, epilepsy, and brain malformations. We systematically reviewed published cases to define the clinical spectrum, characterize the mutational landscape, and explore genotype–phenotype correlations. Methods: We conducted systematic searches of PubMed, Embase, and Web of Science from inception to March 2025, supplemented by GeneReviews and OMIM references. Studies reporting PPP2R1A variants with clinical data were included. Data extraction followed PRISMA guidelines, encompassing study characteristics, genetic findings, and phenotypic features. Results: We identified 16 studies representing 60 patients with PPP2R1A-related disorders. Twenty-six distinct pathogenic variants were identified; these were predominantly de novo heterozygous missense changes clustering within HEAT repeats 5–7. Recurrent hotspots included p.Arg182Trp (n = 12) and p.Arg183Gln (n = 5). Developmental delay and intellectual disability were universally present in all patients for whom data were available (100%, 58/58). Epilepsy occurred in 50.9% (29/57), and structural brain abnormalities in 83.1% (49/59), with corpus callosum abnormalities (40.7%, 24/59) and ventriculomegaly (32.2%, 19/59) being most frequent. Microcephaly was reported in 17.2% (10/58) and macrocephaly in 25.9% (15/58), while dysmorphic features were present in 53.4% (31/58). The phenotypic spectrum ranged from severe neonatal presentations with high mortality to milder neurodevelopmental courses, with prenatal manifestations including ventriculomegaly, corpus callosum abnormalities, and rare cardiac defects. Clear genotype–phenotype correlations emerged, with HEAT5 variants (p.Arg182Trp, p.Arg183Gln) associated with severe phenotypes and increased mortality, while p.Arg258His variants demonstrated comparatively milder courses. Conclusions: PPP2R1A-related disorders encompass a broad clinical spectrum ranging from lethal neonatal disease to survivable forms with variable neurodevelopmental outcomes. Prenatal features including ventriculomegaly and corpus callosum abnormalities enable early genetic diagnosis, informing reproductive counseling. Recognition of recurrent hotspot variants and their phenotype associations facilitates diagnosis, prognosis, and genetic counseling. These findings provide evidence-based guidance for clinical management and highlight the importance of variant-specific prognostication in this emerging neurodevelopmental disorder. Full article

Background: Pembrolizumab has reshaped the neoadjuvant treatment landscape for triple-negative breast cancer (TNBC). However, the influence of BRCA1/2 mutational status on the efficacy of chemo-immunotherapy remains unclear, particularly in real-world settings. Since BRCA-mutated tumors exhibit homologous recombination deficiency (HRD) and high genomic instability, they may be more immunogenic and responsive to immune checkpoint inhibitors. This multicenter study investigated the association between BRCA1/2 mutations and pathologic complete response (pCR) in TNBC patients treated with pembrolizumab-based neoadjuvant chemotherapy (NACT). Methods: We retrospectively analyzed 184 patients with stage II–III TNBC treated between 2021 and 2024 across eleven Italian oncology centers. All received pembrolizumab combined with platinum- and taxane-based NACT followed by anthracyclines, according to the KEYNOTE-522 regimen. Germline BRCA1/2 status was determined by next-generation sequencing. The primary endpoint was pCR, defined as ypT0/is ypN0. Fisher’s exact test and logistic regression models were used to assess associations between clinical–pathological variables and pCR. Results: Among 184 patients, 25 (13.6%) harbored BRCA1 mutations, 12 (6.5%) BRCA2 mutations, and 147 (79.9%) were wild-type. pCR was achieved in 80.0% of BRCA1-mutated, 75.0% of BRCA2-mutated, and 61.1% of wild-type tumors. When pooled, BRCA1/2-mutated cases showed a higher likelihood of achieving pCR (78.4% vs. 61.1%; odds ratio [OR] = 2.17; 95% CI 1.01–4.97; p = 0.056). High tumor-infiltrating lymphocytes (≥30%) were also associated with increased pCR rates. The frequency of BRCA mutations (20.1%) was consistent with that reported in major TNBC series. No comparative analysis of toxicity or survival outcomes was performed due to the retrospective design and limited follow-up. Conclusions: In this multicenter real-world cohort, TNBC patients carrying BRCA1/2 mutations exhibited a trend toward higher pCR rates with pembrolizumab-based NACT compared with wild-type tumors. These findings suggest enhanced chemosensitivity and immune responsiveness in BRCA-deficient disease, warranting further validation in larger prospective studies with survival endpoints. Full article

Background: A comprehensive temporal analysis of mtDNA haplogroup variation across Lithuanian history remains limited. This study investigates the mtDNA variation landscape during the Iron Age by comparing newly reported Iron Age individual mtDNA data with the new data from present-day Lithuanians. Methods: Remains of individuals from the Iron Age Lithuania (n = 101) were processed using standard protocols for ancient DNA processing. For the present-day Lithuanians (n = 279), whole mitogenomes were sequenced. Thirty-six polymorphic sites within the Hypervariable Region I were used for haplogroup assignment, phylogenetic and population genetic analyses. Results: Fifteen distinct haplogroups in the Iron Age and the present-day Lithuanians were identified. Haplogroup R0/H remained the most frequent across time. Haplogroups U, T, and N were prominent in the Iron Age. Haplogroups M and D were introduced after the Iron Age. Phylogenetic and population genetic analyses revealed greater mtDNA diversity in the present-day Lithuanians. Significant difference in molecular variance was observed during the Iron Age. Barring the Viking period, the Iron Age mtDNA variation matched the present-day Lithuanian and European populations. Conclusions: Our study showed that mtDNA variation over time remained stable with some random fluctuations and gained more diversity in the present-day Lithuanians. Full article

Background/Objectives: Despite decades of technological progress, the diagnosis of dental caries still depends largely on subjective, operator-dependent assessment, leading to inconsistent detection of early lesions and delayed intervention. Artificial intelligence (AI) has emerged as a transformative approach capable of standardizing diagnostic performance and, in some cases, surpassing human accuracy. This scoping review critically synthesizes the current evidence on AI for caries detection and examines its true translational readiness for clinical practice. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science (WoS), covering studies published from January 2019 to June 2024, in accordance with PRISMA-ScR guidelines. Eligible studies included original research evaluating the use of AI for dental caries detection, published in English or Spanish. Review articles, editorials, opinion papers, and studies unrelated to caries detection were excluded. Two reviewers independently screened, extracted, and charted data on imaging modality, sample characteristics, AI architecture, validation approach, and diagnostic performance metrics. Extracted data were summarized narratively and comparatively across studies using tabulated and graphical formats. Results: Thirty studies were included from an initial pool of 617 records. Most studies employed convolutional neural network (CNN)-based architectures and reported strong diagnostic performance, although these results come mainly from experimental settings and should be interpreted with caution. Bitewing radiography dominated the evidence base, reflecting technological maturity and greater reproducibility compared with other imaging modalities. Conclusions: Although the reported metrics are technically robust, the current evidence remains insufficient for real-world clinical adoption. Most models were trained on small, single-source datasets that do not reflect clinical diversity, and only a few underwent external or multicenter validation. Until these translational and methodological gaps are addressed, AI for caries detection should be regarded as promising yet not fully clinically reliable. By outlining these gaps and emerging opportunities, this review offers readers a concise overview of the current landscape and the key steps needed to advance AI toward meaningful clinical implementation. Full article

Background: The development of later-line drugs for metastatic colorectal cancer (mCRC) has expanded treatment options. However, real-world evidence of treatment sequences and transition rates from early- to later-line treatments are limited. Patients and methods: This was a retrospective study using hospital administrative data from patients in Japan who underwent colorectal cancer surgery or first-line treatment after January 2017. Transition rates were calculated and treatment sequences were summarized using a Sankey diagram. Logistic regression was performed to identify factors associated with the transition from second- to third-line treatment. Results: In total, 27,100 patients (median age: 69 years) were included in the study population. Transition rates to subsequent treatment lines from first to fifth ranged from 66.6% to 71.3% (first to second: 69.4%; second to third: 71.3%; third to fourth: 71.1%; fourth to fifth: 66.6%). Among 9061 patients who received second-line treatment, 6456 continued to third-line treatment, and 2605 received the best supportive care. Longer first- (≥180 days; OR: 1.24; 95% CI: 1.13–1.37) and second-line (≥120 days; OR: 1.70; 95% CI: 1.55–1.86) treatment durations were significant factors for continuing to third-line treatment. Prior therapy with oxaliplatin and irinotecan plus molecular targeted drugs was also associated with a higher likelihood of proceeding to third-line treatment (OR: 1.41; 95% CI: 1.27–1.56). Conclusions: This study describes the current mCRC treatment landscape in Japan. Considering the findings, appropriate early treatments are critical for transition to later-line treatment. Additionally, many later-line options are necessary to provide treatment continuation opportunities for better outcomes. Full article

(1) Background: ‘Chaling’ common wild rice (CLWR), one of the two wild rice populations with the northernmost natural distribution worldwide, exhibits excellent cold tolerance. The role of microRNA (miRNA) in regulating cold tolerance in plants has been reported in some species. However, the miRNA landscape in CLWR remains unexplored. (2) Methods: We assessed cold tolerance in CLWR and the conventional rice variety 9311 at 4 °C, and conducted small RNA sequencing and analysis on eight samples from both CLWR and 9311, before and after cold treatment. (3) Results: All seedlings of CLWR survived after cold treatment and recovery, while all seedlings of 9311 died. After quality control and classification analysis of the small RNA sequences, numerous known and novel microRNAs (miRNAs) were identified. The expression analysis showed 59 differentially expressed miRNAs in CLWR before and after cold treatment, and 19 in 9311, with eight overlapping differentially expressed miRNAs between the two varieties. Target gene prediction for these miRNAs indicated that some predicted target genes, such as CTB4a and GRF4, are key genes involved in regulating cold tolerance in rice. Additionally, CLWR actively mobilizes more miRNAs and their target genes to resist cold stress than 9311. (4) Conclusions: This study offers new insights into the regulatory mechanisms of cold tolerance in CLWR at the miRNA level, providing a wealth of gene (miRNA) resources for genetic breeding research in rice aimed at enhancing cold tolerance. Full article

Background/Objectives: Sirtuin 7 (SIRT7), a nuclear NAD⁺-dependent deacylase, plays multifaceted and sometimes opposing roles in tumorigenesis. By preserving chromatin architecture and genome integrity, SIRT7 protects against malignant transformation; however, once cancer is established, it can either sustain or restrain tumor growth through context-dependent signaling programs, albeit via largely unknown mechanisms. Recent findings have uncovered an additional—and previously underappreciated—dimension: SIRT7’s capacity to modulate anti-cancer immunity. This review revisits the current understanding of SIRT7 in cancer by emphasizing its emerging immunomodulatory functions and influence on the tumor microenvironment. Methods: We conducted a comprehensive literature review up to October 2025 using the PubMed database to identify both tumor-intrinsic and tumor-extrinsic mechanisms linking SIRT7 to anti-cancer immunity and to relate the established molecular functions of SIRT7—such as its roles in metabolism, genome maintenance, and inflammatory regulation—to immune regulation. Results: SIRT7 directly regulates immune checkpoint expression and T cell metabolic fitness, thereby positioning it as a key node connecting tumor-intrinsic programs with immune surveillance. Moreover, by controlling molecular pathways such as metabolism, genomic stability, and inflammatory responses—both within cancer cells and across other components of the tumor microenvironment—SIRT7 may more broadly influence the immune landscape, orchestrating immune evasion or recognition. Conclusions: Deciphering how SIRT7’s tumor-intrinsic and immunomodulatory functions intersect is essential for anticipating the consequences of its pharmacological targeting in cancer. A deeper understanding of this interplay will enable the rational design of combination strategies that integrate SIRT7 modulation with immunotherapy within a precision medicine framework. Full article

Background: Among primary malignant brain tumors in adults, glioblastoma is the most common and the most aggressive, characterized by profound metabolic reprogramming. This metabolic shift is essential for sustaining relentless proliferation and adapting to the challenging tumor microenvironment (TME). Central to this adaptation in glioma is the Warburg effect, which leads to excessive lactate production and accumulation, even in the presence of oxygen. This metabolic divergence significantly impacts the tumor immune microenvironment, promoting the recruitment of immunosuppressive cells and weakening the anti-tumor immune response. Core Content: This review provides a comprehensive analysis of the multifaceted roles of lactate in IDHwt glioma pathogenesis. It explores how lactate serves as a critical nexus connecting aberrant metabolism, epigenetic reprogramming (notably via histone lactylation), and immune evasion. The review delves into the molecular mechanisms by which lactate, particularly through the post-translational modification known as lactylation, directly modulates the epigenetic landscape to promote oncogene expression. Furthermore, it examines lactate’s role in acidifying the TME, promoting the immunosuppressive M2 polarization of glioma-associated macrophages (GAMs), and inhibiting the cytotoxic activity of T lymphocytes. Conclusions: This “lactate-centric” framework provides a unifying model that links metabolic dysregulation directly to malignant progression and therapeutic resistance (e.g., to TMZ). By elucidating this metabolic–epigenetic–immune axis, the review highlights a critical dependency that fuels glioma aggression. Finally, it discusses emerging therapeutic strategies aimed at targeting lactate production (LDHAi), transport (MCTi), and downstream epigenetic signaling (HDACi/p300i), offering novel avenues for integrative immunometabolic therapy. Full article

Background/Objective: Genetic factors contribute significantly to Parkinson’s disease (PD), especially in cases with early onset or positive family history. However, previous investigations of the genetic landscape in PD populations were mainly based on targeted genotyping. The aim of this study was to investigate the prevalence of pathogenic variants in known PD-associated genes in a series of Swedish PD patients. Methods: We performed whole-exome sequencing on 285 PD probands from southern Sweden. Our series was enriched for patients with early disease onset or positive family history. We focused on 44 genes previously linked to PD. Results: We identified a CHCHD2 p.(Phe84LeufsTer6) frameshift variant in two unrelated patients and report the first PD case of Swedish ancestry carrying the VPS35 p.(Asp620Asn) variant. Additionally, in one patient each, we found an SNCA duplication, an SNCA p.(Ala53Thr) variant, and a LRRK2 p.(Gly2019Ser) variant. Thus, only 2.1% (n = 6) of patients in this series had Mendelian monogenic PD forms. In addition, forty-three patients carried variants in GBA1, including T369M, which may lack disease-association in our population (n = 12); E326K (n = 22), which is classified as a PD risk variant; as well as N370S (n = 3), R329H (n = 3), S107L (n = 1), and L444P (n = 1), with one patient harboring both T369M and E326K. Pathogenic variants in ARSA, ATP7B, and PRKN genes were also detected in heterozygote form, but their role in PD remains uncertain. Conclusions: Monogenic forms of PD are rare in southern Sweden, even among the familial and early-onset PD patients that were overrepresented in our study. Our findings highlight the genetic diversity in Swedish PD patients and identify key variants for further functional and clinical studies. Full article

Background: Pathogenic variants in interphotoreceptor matrix proteoglycan 1 (IMPG1) have been associated with autosomal dominant and recessive retinitis pigmentosa (RP) and autosomal dominant adult vitelliform macular dystrophy (AVMD). Monoallelic pathogenic variants in IMPG2 have been linked to maculopathy and biallelic variants to RP with early onset macular atrophy. Herein we characterise the phenotypic and genotypic features of patients with IMPG1/IMPG2 retinopathy and report novel variants. Methods: Patients with IMPG1 and IMPG2 variants and compatible phenotypes were retrospectively identified. Clinical data were obtained from reviewing the medical records. Phenotypic data included visual acuity, imaging included ultra-widefield pseudo-colour, fundus autofluorescence, and optical coherence tomography (OCT). Genetic testing was performed using next generation sequencing (NGS). Variant pathogenicity was investigated using in silico analysis (SIFT, PolyPhen-2, mutation taster, SpliceAI). The evolutionary conservation of novel missense variants was also investigated. Results: A total of 13 unrelated patients were identified: 2 (1 male; 1 female) with IMPG1 retinopathy and 11 (7 male; 4 female) with IMPG2 retinopathy. Both IMPG1 retinopathy patients were monoallelic: one patient had adult vitelliform macular dystrophy (AVMD) with drusenoid changes while the other had pattern dystrophy (PD), and they presented to clinic at age 81 and 72 years, respectively. There were 5 monoallelic IMPG2 retinopathy patients with a maculopathy phenotype, of whom 1 had PD and 4 had AVMD. The mean age of symptom onset of this group was 54.2 ± 11.8 years, mean age at presentation was 54.8 ± 11.5 years, and mean BCVAs were 0.15 ± 0.12 logMAR OD and −0.01 ± 0.12 logMAR OS. Six biallelic IMPG2 patients had RP with maculopathy, where the mean age of onset symptom onset was 18.4 years, mean age at examination was 68.7 years, and mean BCVAs were 1.90 logMAR OD and 1.82 logMAR OS. Variants in IMPG1 included one missense and one exon deletion. A total of 11 different IMPG2 variants were identified (4 missense, 7 truncating). A splicing defect was predicted for the c.871C>A p.(Arg291Ser) missense IMPG2 variant. One IMPG1 and five IMPG2 variants were novel. Conclusions: This study describes the phenotypic spectrum of IMPG1/IMPG2 retinopathy and six novel variants are reported. The phenotypes of PD and AVMD in monoallelic IMPG2 patients may result from haploinsufficiency, supported by the presence of truncating variants in both monoallelic and biallelic cases. The identification of novel variants expands the known genetic landscape of IMPG1 and IMPG2 retinopathies. These findings contribute to diagnostic accuracy, informed patient counselling regarding inheritance pattern, and may help guide recruitment for future therapeutic interventions. Full article

Background/objectives: Studies evaluating the longitudinal impact (beyond a decade) of antibiotic stewardship programs (ASPs) on the volume/quality of antibiotic prescriptions, as well as the impact on antibiotic resistance, are lacking. Since 2008, the ASP at Singapore General Hospital has implemented various strategies in the following phases: (1) initiation, (2) expansion, (3) optimisation, and (4) innovation. In this study, we aim to evaluate the volume/quality of antibiotic prescribing and susceptibility trends of clinically significant Gram-negative bacilli (GNBs), along with the evolution of ASP strategies over time. Methods: We conducted a single-centre, retrospective observational study from 2011 to 2024. Antibiotic consumption, appropriateness, and susceptibility trends of six GNBs to seven commonly used antibiotics were analysed using the Kendall tau test to identify potential monotonic trends based on aggregated rather than patient-level data. Results: We demonstrated sustained improvement in appropriateness of seven broad-spectrum IV antibiotics, accompanied by significant reductions in IV ciprofloxacin, cefepime, and ertapenem use (p < 0.05). Hospital-wide susceptibility of six GNBs to all evaluated antibiotics improved significantly (p < 0.05), except for E. coli’s susceptibility to ertapenem and Enterobacterales’s susceptibility to ciprofloxacin. Conclusions: With an evolving, multi-pronged stewardship approach, antibiotic prescribing and GNB susceptibility to most antibiotics have improved. In a rapidly evolving healthcare landscape, ASPs must remain agile, continually refining priorities and employing innovative strategies. Full article

Background and Objectives: Cancer incidence patterns in South Korea have shifted markedly over the past two decades, with notable increases among younger generations. Despite growing concern regarding early-onset cancer, comprehensive assessments of long-term age-, period-, and cohort-specific trends across multiple cancer types remain limited. This study examined nationwide cancer incidence trends from 2001 to 2020 using Joinpoint regression and age–period–cohort (APC) modeling. Materials and Methods: A population-based analysis was conducted using Korea Central Cancer Registry (KCCR) data, including all primary malignant tumors diagnosed from 2001 to 2020. Incidence rates were calculated by sex and 5-year age groups and standardized to the mid-2000 Korean population. Joinpoint regression estimated annual percent change (APC) and average annual percent change (AAPC), accounting for overdispersion and autocorrelation. Independent temporal effects were evaluated through APC modeling using overlapping 10-year birth cohorts, with the 1961 cohort as the reference. Results: Incidence increased for prostate, kidney, breast, and pancreatic cancers, while stomach, liver, lung, and biliary cancers showed continued declines. Colon cancer rose until 2011 and decreased thereafter. More recent birth cohorts exhibited higher risks for prostate, kidney, and pancreatic cancers, whereas older cohorts showed elevated risks for stomach, liver, colon, and biliary cancers. Lung cancer trends diverged by sex, decreasing among men but increasing among women. Conclusions: Marked heterogeneity in long-term incidence patterns across cancer types and generations was identified. Rising rates of lifestyle- and obesity-associated cancers in more recent cohorts highlight the need for continued surveillance and targeted prevention strategies. APC-based evaluation provides essential insight into Korea’s evolving cancer landscape and supports future public health planning. Full article