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PubMed1992

[Increased risk factors for the occurrence of bladder cancer].

Risk factors of bladder cancer development were studied in a population-based case-control epidemiological study performed in Moscow. Relative risk (RR) indexes appeared to be increased in smokers (4.2) and ex-smokers (3.5) with statistically significant trends for two most important factors such as duration of smoking and duration of withdrawal. A pronounced although insignificant increase in the RR indexes was established for drivers (3.0) and a slight insignificant rise-for gas arc welding operators (1.5). The indexes were increased in subjects with a family history of cancer. The relative risk of cancer was significantly lower in beta-carotene consumers. A preventive effect of polyunsaturated fatty acids and oil and margarine used for frying was established. Risk of bladder cancer tended to increase with a rise in dietary protein. A dose-effect type inhibition of advancement of the disease by vitamin C was observed.

Adult↗

PubMed1995

Strenuous physical activity in young adulthood and risk of breast cancer (United States).

The epidemiologic data on the relation between strenuous physical activity and breast cancer are limited and inconsistent. Because risk of breast cancer may be influenced by ovarian function which, in turn is modulated by physical activity, the hypothesis that exercise may be associated with a reduced risk of breast cancer merits further investigation. We, therefore, conducted a large case-control study in 1988-1991, and interviewed 6,888 women (17 to 74 years of age) with breast cancer in Maine, Massachusetts, New Hampshire, and Wisconsin (United States). Interviewed controls (9,539 women, 18 to 74 years of age) were selected randomly from lists of licensed drivers (for younger women) or from a roster of Medicare enrollees (for older women). We used multivariate adjusted odds ratios (OR) and 95 percent confidence intervals (CI) from logistic regression models to estimate relative risks between self-reported physical activity when 14 to 22 years of age and breast cancer. When compared with sedentary controls, women who reported any strenuous physical during ages 14 to 22 years had a modest reduction in the risk of breast cancer (OR = 0.95, CI = 0.93-0.97). However, those who exercised vigorously at least once a day had a 50 percent reduction in risk of breast cancer (OR = 0.5, CI = 0.4-0.7). These data support the hypothesis that women who are physically active have a reduced risk of breast cancer.

Adolescent↗

PubMed2026

The landscape of clonal hematopoiesis of indeterminate potential in long-term breast cancer survivors.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) can confound blood-based genomics and may be shaped by cytotoxic therapy; clarifying its persistence after breast-cancer chemotherapy is relevant for long-term survivorship follow-up. PATIENTS AND METHODS: Buffy-coat whole-exome sequencing was performed in 189 stage I-III breast-cancer survivors with blood collected a median 136.5 months after diagnosis. CHIP was assessed using a prespecified 100-gene hematopoietic-driver compendium and exome-wide interrogation. Clinical associations were assessed with univariable tests and multivariable logistic regression including chemotherapy, radiotherapy, age, smoking and obesity. RESULTS: Within the 100-gene compendium, 54/189 (28.6%) patients harbored ≥1 variant, predominantly missense, with DNMT3A and TET2 predominating and multi-hit cases rare. In multivariable models, chemotherapy was not associated with panel-defined CHIP (OR 0.77; 95% CI 0.40-1.48; p = 0.432). Similarly, age, adjuvant radiotherapy, obesity and smoking status were not significantly associated with panel-defined CHIP. Gene-level comparisons showed no differences by chemotherapy exposure. Exome-wide, 67/189 (35.4%) patients carried ≥1 variant; chemotherapy was not associated with exome-wide variant positivity (OR 0.89; 95% CI 0.48-1.67; p = 0.721), and no locus differed between chemotherapy-exposed and never-exposed women. CONCLUSION: Buffy-coat WES performed in long-term breast cancer survivors shows no cohort-level association between prior chemotherapy and increased CHIP.

Humans↗

PubMed2007

Cost of breast cancer in Sweden in 2002.

Breast cancer is the most common cancer among Swedish women and an important cause of illness and death. The aim of this study was to estimate the total cost of breast cancer in Sweden in 2002, using a top-down prevalence-based cost-of-illness approach. The total cost of breast cancer in Sweden in 2002 was estimated at 3.0 billion SEK (1 euro = 9.4 SEK). The direct costs were estimated at 895 million SEK and constituted 30% of the total cost. Indirect costs were estimated at 2.1 billion SEK and constituted 70% of the total cost. The main cost driver was production losses caused by premature mortality, amounting to 52% of the indirect costs. The reason that indirect costs were the dominant cost is because most newly detected breast cancers occur in patients aged below 65, thus causing significant production losses due to sick leave, early retirement, and premature mortality.

Age Factors↗

PubMed1994

Incidence of selected cancers in Swedish railway workers, 1961-79.

Among all Swedish men, 20 to 64 years of age and employed in 1960, railway workers were selected and compared with the population at large, concerning the incidence of leukemia, lymphoma, tumors of the brain, breast, and the pituitary gland. The study was a re-analysis of the 1961-79 incidence data previously showing no increase in risk for leukemia and brain tumors for railway workers. In the present study, follow-up was divided into two 10-year periods, and elevated relative risks (RR) were found for the first decade. For the first decade, engine drivers and conductors combined had an RR of chronic lymphocytic leukemia, acute myeloid leukemia, and lymphoma of 1.9 (95 percent confidence interval [CI] = 0.9-4.0), 1.4 (CI = 0.4-4.3), and 1.0 (CI = 0.5-1.9), respectively. For all brain tumors, the RR was 1.2 (CI = 0.8-1.9), with a higher risk estimate for those below age 30 (RR = 12.2, CI = 2.8-52.5). Three cases of breast cancer and nine cases of tumors of the pituitary gland occurred among engine drivers and conductors, corresponding to RRs of 4.9 (CI = 1.6-11.8) and 3.2 (CI = 1.6-6.2), respectively. Work on trains entails extremely high exposure to low frequency magnetic fields (EMF). The results give some support to the hypothesis of an association between EMF and certain types of cancers. The outcome for the pituitary gland, being a focal point of hormonal regulation, suggests a hormonal link.

Acute Disease↗

PubMedDate not supplied

[The first anti-cancer center in Lyon (1923): surgeon Leon Berard and Auguste Lumiere].

At present, little is known about the creation of cancer hospitals. I will report on that of Lyons, France, with the famous surgeon, Léon Bérard (1870-1956). A specialist of neck surgery, he was the first to carry out major thoracoplasties. The cancer hospital was inaugurated in 1923 under the Great Dome of the hôtel-Dieu hospital. (The dome is the creation of the famous architect Germain Soufflot (1748)). In 1933, the cancer hospital moved in the newly-built Edouard Herriot Hospital; it became independent in 1958, two years after the famous surgeon's death, and it was rightly named after him: "Centre anticancéreux Léon Bérard". Its creation and its quick development owes a lot to generosity of Auguste Lumière, one of the two inventors of cinematograph. Auguste Lumière sponsored radiotherapy material and, at Léon Bérard's request (as there was a lack of space in Edouard Herriot hospital), created a centre for cancer patients (Bon Abr Hospital, rue Mistral, with Dr Vigne). A Lumière gave his time as well as his money for the centre; he was the car-driver, he helped L. Bérard with his university classes, and he often comforted the patients while running a private clinic (La Clinique Lumière), which combined dispensary services with research. (Micheline Bonin)

Cancer Care Facilities↗

PubMed2006

Measurement of protection afforded by ultraviolet-absorbing window film using an in vitro model of photodamage.

BACKGROUND AND OBJECTIVES: The effects of chronic sun damage including telangiectasias, solar lentigos, rhytides, enlarged pores, sagging skin, and pre-cancerous and cancerous growths are among the most common presenting complaints in a dermatologist's office. These changes are often worse on the driver's side of the face, emphasizing the role of UVA exposure received while driving in producing these changes. This study was undertaken to measure the ability of car window glass alone and in combination with ultraviolet (UV)-absorbing film to reduce UV-damage as measured using an established in vitro model of photoprotection. STUDY DESIGN MATERIALS AND METHODS: Using the 3T3 neutral red uptake photoprotection assay with solar simulating radiation (SSR) administered by a xenon arc solar simulator, we measured the photoprotection ability of auto glass, window film that filters UV radiation, and the combination of window film and auto glass. RESULTS: As measured by the 3T3 neutral red uptake photoprotection assay, auto glass reduced cell death from SSR by 29%, while window film reduced it 90%, and the combination of auto glass and film reduced cell death by 93%, when compared to unfiltered SSR. CONCLUSIONS: Window film that filters UV radiation results in dramatic reductions in cytotoxicity when measured by the neutral red uptake photoprotection assay. Widespread use of window film provides an ever-present barrier to ultraviolet A (UVA) exposure and could potentially reduce the detrimental effects of UVA, including photoaging, skin cancer, and ocular damage, such as cataracts. In addition, such film is essential for patients suffering from conditions sensitive to UV radiation, such as lupus erythematosis.

Animals↗

PubMed2026

Genomic Landscape of 6597 Hong Kong HBOC Patients: Implications for Beyond-BRCA Multi-Gene Panel Testing and Cancer Surveillance.

Breast cancer remains highly prevalent, where the lifetime risk before age 75 is one in 13. However, known genetic factors were only identified in 14.7% of cases in our Hong Kong Hereditary Breast Cancer Family Registry. Our current local policy for genetic testing does not cover the detection of beyond BRCA1/2. Here we highlight the clinical value of extending testing to beyond BRCA susceptibility genes for improved prevention, diagnosis, and management. We recruited 6597 hereditary breast and ovarian cancer (HBOC) patients from our registry based on family history and clinical criteria. Germline mutations were identified by multi-gene sequencing analysis using next-generation sequencing (NGS). Clinical-pathological characteristics of BRCA and beyond BRCA carriers were compared and the real-world management and surveillance services adopted in Hong Kong were highlighted. In this multi-gene hereditary cancer cohort, germline mutations were identified in 10.9% of cases for BRCA1/2 and 3.5% for beyond BRCA susceptibility genes. These beyond BRCA mutations constitute a considerable proportion of actionable hereditary risk. Notably, PALB2 emerged as the most prevalent non-BRCA gene, followed by TP53, ATM, and BARD1. New cancers or recurrences were detected during their surveillance; the overall pick up rates were 8.3% (PALB2), 29.4% (TP53), 33.3% (PTEN) and 5.6% (BARD1). This study provides the first comprehensive characterization of the beyond BRCA germline landscape in a Hong Kong hereditary cancer cohort and highlights the current need for implementing multi-gene sequencing analysis and surveillance services for HBOC patients, establishing the predominant non-BRCA drivers and providing a robust empirical basis for expanding public genetic screening frameworks.

Humans↗

PubMedDate not supplied

Local and national uses of a Road to Recovery evaluation.

Evaluation fellows from the George Washington University School of Public Health and Health Services conducted an evaluation of the Road to Recovery program of the Mid-Atlantic division of the American Cancer Society. The evaluation included qualitative analysis of program operation, mailed surveys, in-depth interviews with patients and drivers, and interviews with social workers from treatment centers. Results indicated that patients and drivers were satisfied with the program. Patients appreciated the ability of drivers to provide personalized, reliable service. The recruitment of sufficient drivers to meet transportation demand was a problem. High staff turnover and a lack of electronic tracking of standard information hindered program monitoring. A Mid-Atlantic Advisory Transportation Group reviewed the findings and made recommendations for service improvement. The Mid-Atlantic division evaluation contributed to an "evaluation synthesis" in which participants from the three divisions that had conducted Road to Recovery evaluations examined study data and made recommendations for reorganizing the national transportation program. A Transportation Program Design Team then held fact-finding meetings and adopted goals and objectives for a new national transportation program. The primary lesson learned was the far-reaching effects that a single program evaluation may have for various stakeholders and for an organization.

Cooperative Behavior↗

PubMed1996

A comparative study of the risk factors for lung cancer in Guangdong, China.

A case-control study involving 390 lung cancer cases, matched 1:1 with controls, was carried out in Guangdong Province to compare risk factors for different histopathologic types of lung cancer in both sexes. Female and male lung cancers appear to differ in epidemiological characteristics, pathologic types, and risk factors. The 291 lung cancer cases in males were predominantly squamous cell lung carcinoma (squamous cell carcinoma/adenocarcinoma = 1:0.5), whereas the 99 female lung cancer cases were predominantly adenocarcinoma (squamous cell carcinoma/adenocarcinoma = 1:2.7). The age at which lung cancer was first diagnosed was lower for females than for males (P < 0.0001). Single-factor conditional logistic regression analysis showed an association of lung cancer with family history of tumors, family history of lung cancer, history of chronic bronchitis/emphysema, history of tuberculosis, history of other lung disease, smoking, exposure to environmental tobacco smoke (ETS) in the home and in the workplace, being professional drivers, use of oral contraceptives, and consumption of pickled and salted fish (P < 0.05). Further multivariate logistic regression analysis showed that family history of tuberculosis, history of chronic bronchitis/emphysema, family history of tumors, smoking, exposure to ETS in the home and in the workplace, and consumption of pickled and salted fish were independent risk factors for lung cancer. Using log-linear model analysis, it was confirmed that lung cancer had significant interactions with chronic bronchitis/emphysema, exposure to ETS, history of tuberculosis and smoking. Smoking, however, could only explain 1/5 of the incidence of female lung cancers. Family history of lung cancer and the use of oral contraceptives were related to lung cancer in women. Except for a weak relationship with history of chronic bronchitis/emphysema, adenocarcinoma was found to have no association with the other risk factors.

Adult↗

PubMed2026

Mitochondrial DNA in lung cancer: From biology to clinical implications.

Mitochondrial DNA (mtDNA) is emerging as a relevant component of the molecular landscape in non-small cell lung cancer (NSCLC). Due to its inherent vulnerability to environmental carcinogens, the mitochondrial genome accumulates alterations-such as D-loop and Electron Transport Chain variants- increasingly identified as potential mediators of tumor development and metabolic shifts. Recent findings highlight potential clinical applications of mtDNA. In diagnostics, emerging models based on cf-mtDNA fragmentomics and tRNA-derived fragments have shown promising capabilities for early-stage diagnosis. Prognostically, somatic variants in Complex I and specific mitochondrial lncRNA signatures have been evaluated as independent indicators of overall survival and metastatic risk. Furthermore, mitochondrial mass may potentially support chemotherapy election. Additionally, horizontal transfer of mitochondria to tumor-infiltrating lymphocytes offers a novel framework for understanding resistance to immunotherapy. While these preliminary results provide a promising roadmap for molecular stratification, their integration into routine practice remains a goal that requires further prospective validation in larger, multi-ethnic cohorts to ensure reproducibility and to distinguish functional drivers from passenger variants. Collectively, these emerging findings suggest that mtDNA analysis represents a valuable complementary approach to precision oncology in lung cancer.

Humans↗

PubMed2004

A randomized trial of direct mailing of fecal occult blood tests to increase colorectal cancer screening.

BACKGROUND: Although colorectal cancer screening by using a fecal occult blood test (FOBT), flexible sigmoidoscopy, colonoscopy, or barium enema x-ray reduces the incidence of and death from colorectal cancer, the rate of colorectal cancer screening in the general population is low. We conducted a randomized trial consisting of direct mailing of FOBT kits to increase colorectal cancer screening among residents of Wright County, Minnesota, a community in which colorectal cancer screening was promoted. METHODS: At baseline, we mailed a questionnaire about colorectal cancer screening to a random sample of Wright County residents aged 50 years or older who were randomly selected from the Minnesota State Driver's License and Identification Card database (estimated N = 1451). The sample was randomly allocated into three equal subgroups: one group (control) received only the questionnaire, one group received FOBT kits by direct mail with reminders, and one group received FOBT kits by direct mail without reminders. Study participants were sent a follow-up questionnaire 1 year after baseline. We used the responses to the questionnaires to estimate the 1-year change in self-reported screening rates in each group and the differences in the changes among the groups, along with the associated bootstrap 95% confidence intervals (CIs). RESULTS: At baseline, the estimated response rate was 86.5%, self-reported adherence to FOBT guidelines was 21.5%, and overall adherence to any colorectal cancer screening test guidelines was 55.8%. The 1-year rate changes in absolute percentage for self-reported adherence to FOBT use were 1.5% (95% CI = -2.9% to 5.9%) for the control group, 16.9% (95% CI = 11.5% to 22.3%) for the direct-mail-FOBT-with-no-reminders group, and 23.2% (95% CI = 17.2% to 29.3%) for the direct-mail-FOBT-with-reminders group. The 1-year rate changes for self-reported adherence to any colorectal cancer screening test were 7.8% (95% CI = 3.2% to 12.0%) for the control group, 13.2% (95% CI = 8.4% to 18.2%) for the direct-mail-FOBT-with-no-reminders group, and 14.1% (95% CI = 9.1% to 19.1%) for the direct-mail-FOBT-with-reminders group. CONCLUSION: Direct mailing of FOBT kits combined with follow-up reminders promotes more rapid increases in the use of FOBT and nearly doubles the increase in overall rate of adherence to colorectal cancer screening guidelines in a general population compared with a community-wide screening promotion and awareness campaign.

Aged↗

PubMedDate not supplied

Diversity in the association between occupation and lung cancer among black and white men.

A population-based case comparison study of incident lung cancer and occupational risk factors was conducted in the tricounty Detroit metropolitan area. Nearly 6000 lung cancer cases and a comparison group of 3600 colon cancer cases were interviewed. This report includes 3792 white and black male lung cancer cases and 1966 black and white colon cancer referents. Cigarette smoking, age at diagnosis, and lifetime work history were assessed to determine the relationship between length of employment in specific occupations and industries and lung cancer. Diverse patterns of association between work history and lung cancer were observed for black and white men. Significant associations were seen between lung cancer and increasing length of employment in the following occupations: for white men, concrete and terrazzo finishers, grinding machine operators, heat treating machine operators, miscellaneous machine operators, truck drivers, driver sales, and laborers; for black men, farm workers, automobile mechanics, painting machine operators, furnace operators, and garbage collectors; for both black and white men, farmers, slicing and cutting machine operators, and garbage collectors. Distinct patterns for black and white men also were observed for length of employment by industry. This study clearly demonstrates the need to include black men in studies of occupational cancer etiology and to evaluate black and white men separately. It also indicates the necessity for cigarette smoking history to accurately assess workplace cancer risks. We propose guidelines for incorporating the use of biomarkers into further studies of occupational cancer epidemiology.

Adult↗

PubMed1989

Study of lung cancer histologic types, occupation, and smoking in Missouri.

A case-control study of lung cancer was conducted to evaluate the relationship between lung cancer histologic types and occupation, adjusted for smoking. A total of 4,431 white male cases and 11,326 cancer controls, diagnosed between 1980 and 1985, were identified through the Missouri Cancer Registry. For all histologic types combined, excess risk was observed among many a priori suspected high-risk occupations. Lung cancer was elevated among men employed as insulators (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 0.7, 137.8), carpenters (OR = 1.3; 95% CI = 1.0, 1.7), painters, plasterers, and wallpaper hangers (OR = 2.0; 95% CI = 1.2,3.3), structural metal workers (OR = 1.9; 95% CI = 0.6,6.0), mechanics and repairers (OR = 1.3; 95% CI = 1.0,1.7), motor vehicle drivers (OR = 1.5; 95% CI = 1.2,1.8), police and firefighters (OR = 1.6; 95% CI = 1.1,2.3), and food service personnel (OR = 1.8; 95% CI = 1.0,3.5). A deficit of lung cancer was observed among farmers (OR = 0.9; 95% CI = 0.7,1.0). Adenocarcinoma of the lung was elevated among carpenters (OR = 1.6; 95% CI = 1.0,2.5) and cabinet and furniture makers (OR = 2.0; 95% CI = 0.4,8.1), which is interesting because of the previous reports of excess adenocarcinoma of the nasal cavity associated with wood dust exposure. Adenocarcinomas were also elevated among plumbers (OR = 2.0; 95% CI = 1.0,3.8) and printers (OR = 1.8; 95% CI = 0.7,4.2). Electricians were at slightly increased risk for adenocarcinoma (OR = 1.5; 95% CI = 0.7,2.8) and "other" or mixed cell types of lung cancer (OR = 1.5; 95% CI = 0.8,2.9) but at decreased risk for small cell (OR = 0.8; 95% CI = 0.3,2.0) and squamous cell (OR = 0.8; 95% CI = 0.4,1.6) tumors. Among welders, adenocarcinoma (OR = 1.7; 95% CI = 0.7,3.8) and squamous cell (OR = 1.7; 95% CI = 0.9,3.3) cancers were elevated, but small cell and "other" lung cancers were not. Despite the limitations of the Cancer Registry data, some interesting associations were observed that merit further study, particularly the association between lung adenocarcinoma and occupational exposure to wood and wood dust.

Adenocarcinoma↗

PubMed2026

Drug resistance in breast cancer brain metastasis: mechanisms and therapeutic strategies.

Brain-metastatic breast cancer (BMBC) is a severe complication of advanced breast cancer, affecting 15-30% of metastatic patients, particularly those with HER2-positive or triple-negative subtypes, and is associated with dismal prognosis and median survival under 12 months. Therapeutic resistance, driven by the central nervous system's sanctuary role, poses a major barrier to effective treatment, often resulting in discordant intracranial versus extracranial responses. This comprehensive review highlights BMBC resistance mechanisms, drawing from preclinical models, clinical studies, and genomic analyses. Key drivers include genetic/epigenetic alterations, BBB-mediated drug exclusion via efflux transporters, and microenvironmental interactions with astrocytes and immune cells that promote survival signaling. Additional factors encompass cancer stem cell plasticity/dormancy enabling therapy evasion, metabolic reprogramming and extracellular matrix remodeling that shields tumor from drugs. We highlight how these interconnected pathways create a protective niche for metastatic cells. Promising strategies to overcome resistance include BBB-penetrant agents, antibody-drug conjugates, nanomedicine, and combination therapies targeting the tumor microenvironment and epigenetics. By integrating mechanistic insights with translational opportunities, this review emphasizes the potential for personalized, multi-targeted approaches to improve patient outcomes in BMBC.

Humans↗

PubMed2025

Genome-wide diversity of chromosomal inversions and their disease relationships.

Chromosomal inversions shape evolution and are implicated in human disease, yet their effects on genomic variation and health outcomes remain poorly understood. We analyze genome-wide human inversion polymorphisms, contrasting single-event and recurrent loci. Inversion recurrence is validated using structured-coalescent simulations. We show that single-event inversions evolve in near-complete isolation: inverted haplotypes show ~16-fold lower diversity and strong differentiation from direct haplotypes (median FST = 0.33). By contrast, recurrent inversions maintain gene flow, resulting in similar diversity across orientations and ~4-fold lower differentiation. We further find marked differences in coding sequence conservation between single-event and recurrent inversions. Using the NIH All of Us biobank, we impute inversions and identify four inversions with significant disease associations. Notably, the 17q21 inversion is associated with reduced risk of cognitive decline (OR=0.919) and breast cancer (OR=0.910) but with increased obesity risk (OR=1.097), consistent with pleiotropic selection. These findings establish inversions as major drivers of human genetic diversity and disease, with evolutionary outcomes critically dependent on recurrence.

Evolution↗

PubMed2026

TNIK Overexpression Is Sufficient for Chemoradiation Resistance in Limited-Stage Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is characterized by early metastasis, intrinsic chemoradiation resistance, and tumor recurrence. Besides the lack of potentially targetable oncogenic drivers, therapeutic advancements are also hindered by the scarcity of surgically resected tissue specimens ideal for profiling studies. We used patient-derived xenografts (PDX) to model SCLC chemoradiation resistance and identified chemoradiation resistance candidate genes using RNA sequencing. Additionally, we used human SCLC cell lines to confirm our in vivo results and delineate the underlying mechanism. Transcriptome profiling showed that the Traf2- and Nck-interacting kinase (TNIK) gene was consistently upregulated in an array of SCLC PDXs exposed to chemoradiation compared with monotherapy, which is consistent with previous observations of TNIK amplification in human samples. Genetic depletion (P < 0.01) or pharmacologic inhibition (P < 0.0001) of TNIK reduced in vitro clonogenic survival of TNIKhigh SCLC cells and promoted sensitivity to chemoradiation. In vivo, pharmacologic inhibition of TNIK enhanced chemoradiation sensitivity (P < 0.0001) of the H446 cell line-derived xenograft (CDX) in NOD-SCID mice. Furthermore, pharmacologic inhibition of TNIK in vivo demonstrated sensitivity (P < 0.0001) to chemoradiotherapy (CRT) in LX33 PDX. These results indicate that TNIK plays a role in conferring resistance to chemoradiation in SCLC cell lines and in vivo in SCLC CDX and PDX models. Delineating the mechanism behind radiosensitization suggested that TNIK inhibition may impair the DNA damage response in irradiated cells. Collectively, these findings suggest that TNIK may be a promising therapeutic target in limited-stage SCLC and support further investigation of TNIK inhibition in combination with standard CRT.

Humans↗

PubMed2026

Protective TGFβ2/SMAD3 axis identified by TWAS in papillary thyroid cancer.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Although generally indolent, a subset shows aggressive behaviour. Furthermore, the genetic heterogeneity of PTC is not fully explained by known driver mutations, underscoring the need to identify additional susceptibility genes and regulatory mechanisms. To identify additional susceptibility genes and regulatory mechanisms, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomisation (SMR), joint/conditional testing (JCT), and colocalisation analyses across multiple independent cohorts, followed by heterogeneity in dependent instruments (HEIDI) test. Gene prioritisation analyses consistently highlighted TGFB2 and SMAD3 as candidate susceptibility genes for PTC, with SMR supporting putative protective effects. Besides, GEPIA confirmed the positive correlation between TGFB2 and SMAD3 expression in TCGA-THCA. Functional experiments in TPC-1 cells showed that TGFβ2 treatment inhibited cell proliferation and migration, induced apoptosis, and resulted in G0/G1 cell-cycle arrest, accompanied by increased SMAD3 phosphorylation, suggesting activation of canonical TGFβ signalling. Collectively, these findings bridge population-based genetic inference with mechanistic validation and suggest convergent evidence supporting a tumour-suppressive role of the TGFβ2/SMAD3 axis in PTC.

Humans↗