RESUMEN
To find sequence variants affecting prostate cancer (PCA) susceptibility in an unscreened Romanian population we use a genome-wide association study (GWAS). The study population included 990 unrelated pathologically confirmed PCA cases and 1034 male controls. DNA was genotyped using Illumina SNP arrays, and 24.295.558 variants were imputed using the 1000 Genomes data set. An association test was performed between the imputed markers and PCA. A systematic literature review for variants associated with PCA risk identified 115 unique variants that were tested in the Romanian sample set. Thirty of the previously reported SNPs replicated (P-value < 0.05), with the strongest associations observed at: 8q24.21, 11q13.3, 6q25.3, 5p15.33, 22q13.2, 17q12 and 3q13.2. The replicated variants showing the most significant association in Romania are rs1016343 at 8q24.21 (P = 2.2 × 10-4 ), rs7929962 at 11q13.3 (P = 2.7 × 10-4 ) and rs9364554 at 6q25.2 (P = 4.7 × 10-4 ). None of the variants tested in the Romanian GWAS reached genome-wide significance (P-value <5 × 10-8 ) but 807 markers had P-values <1 × 10-4 . Here, we report the results of the first GWAS of PCA performed in a Romanian population. Our study provides evidence that a substantial fraction of previously validated PCA variants associate with risk in this unscreened Romanian population.
Asunto(s)
Biomarcadores de Tumor/genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/diagnóstico , Anciano , Anciano de 80 o más Años , Alelos , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Perfilación de la Expresión Génica , Frecuencia de los Genes , Genoma Humano , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Secuencia por Matrices de Oligonucleótidos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Riesgo , RumaníaRESUMEN
Two familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the genes APC and MUTYH, respectively. No information is available on the presence of high-risk CRC mutations in the Romanian population. We performed whole-genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical (IHC) staining for MLH1, MSH2, MSH6, and PMS2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH1, one in MSH6, one in PMS2, and three in APC. Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants (MLH1:p.Lys84ThrfsTer4, MLH1:p.Ala586CysfsTer7, PMS2:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH1:c.1559-1G>C).
Asunto(s)
Poliposis Adenomatosa del Colon/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN/genética , Predisposición Genética a la Enfermedad , Poliposis Adenomatosa del Colon/epidemiología , Poliposis Adenomatosa del Colon/patología , Adulto , Anciano , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , ADN Glicosilasas/genética , Metilación de ADN/genética , Proteínas de Unión al ADN/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Homólogo 1 de la Proteína MutL/genética , Proteína 2 Homóloga a MutS/genética , Mutación , Factores de Riesgo , Rumanía/epidemiologíaRESUMEN
Prostate cancer is the third-most common form of cancer in men in Romania. The Romanian unscreened population represents a good sample to study common genetic risk variants. However, a comprehensive analysis has not been conducted yet. Here, we report our replication efforts in a Romanian population of 979 cases and 1027 controls, for potential association of 34 literature-reported single nucleotide polymorphisms (SNPs) with prostate cancer. We also examined whether any SNP was differentially associated with tumour grade or stage at diagnosis, with disease aggressiveness, and with the levels of PSA (prostate specific antigen). In the allelic analysis, we replicated the previously reported risk for 19 loci on 4q24, 6q25.3, 7p15.2, 8q24.21, 10q11.23, 10q26.13, 11p15.5, 11q13.2, 11q13.3. Statistically significant associations were replicated for other six SNPs only with a particular disease phenotype: low-grade tumour and low PSA levels (rs1512268), high PSA levels (rs401681 and rs11649743), less aggressive cancers (rs1465618, rs721048, rs17021918). The strongest association of our tested SNP's with PSA in controls was for rs2735839, with 29% increase for each copy of the major allele G, consistent with previous results. Our results suggest that rs4962416, previously associated only with prostate cancer, is also associated with PSA levels, with 12% increase for each copy of the minor allele C. The study enabled the replication of the effect for the majority of previously reported genetic variants in a set of clinically relevant prostate cancers. This is the first replication study on these loci, known to associate with prostate cancer, in a Romanian population.
Asunto(s)
Sitios Genéticos , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/genética , Alelos , Estudios de Casos y Controles , Genoma Humano , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Factores de Riesgo , RumaníaRESUMEN
This study assesses the effectiveness of chatbots powered by Large Language Models (LLMs)-ChatGPT 3.5, CoPilot, and Gemini-in delivering prostate cancer information, compared to the official Patient's Guide. Using 25 expert-validated questions, we conducted a comparative analysis to evaluate accuracy, timeliness, completeness, and understandability through a Likert scale. Statistical analyses were used to quantify the performance of each model. Results indicate that ChatGPT 3.5 consistently outperformed the other models, establishing itself as a robust and reliable source of information. CoPilot also performed effectively, albeit slightly less so than ChatGPT 3.5. Despite the strengths of the Patient's Guide, the advanced capabilities of LLMs like ChatGPT significantly enhance educational tools in healthcare. The findings underscore the need for ongoing innovation and improvement in AI applications within health sectors, especially considering the ethical implications underscored by the forthcoming EU AI Act. Future research should focus on investigating potential biases in AI-generated responses and their impact on patient outcomes.
RESUMEN
BACKGROUND: In recent years, the integration of large language models (LLMs) into healthcare has emerged as a revolutionary approach to enhancing doctor-patient communication, particularly in the management of diseases such as prostate cancer. METHODS: Our paper evaluated the effectiveness of three prominent LLMs-ChatGPT (3.5), Gemini (Pro), and Co-Pilot (the free version)-against the official Romanian Patient's Guide on prostate cancer. Employing a randomized and blinded method, our study engaged eight medical professionals to assess the responses of these models based on accuracy, timeliness, comprehensiveness, and user-friendliness. RESULTS: The primary objective was to explore whether LLMs, when operating in Romanian, offer comparable or superior performance to the Patient's Guide, considering their potential to personalize communication and enhance the informational accessibility for patients. Results indicated that LLMs, particularly ChatGPT, generally provided more accurate and user-friendly information compared to the Guide. CONCLUSIONS: The findings suggest a significant potential for LLMs to enhance healthcare communication by providing accurate and accessible information. However, variability in performance across different models underscores the need for tailored implementation strategies. We highlight the importance of integrating LLMs with a nuanced understanding of their capabilities and limitations to optimize their use in clinical settings.
RESUMEN
To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).