RESUMO
Cancer arises from the complex interplay of various factors. Traditionally, the identification of driver genes focuses primarily on the analysis of somatic mutations. We describe a new method for the detection of driver gene pairs based on an epistasis analysis that considers both germline and somatic variations. Specifically, the identification of significantly mutated gene pairs entails the calculation of a contingency table, wherein one of the co-mutated genes can exhibit a germline variant. By adopting this approach, it is possible to select gene pairs in which the individual genes do not exhibit significant associations with cancer. Finally, a survival analysis is used to select clinically relevant gene pairs. To test the efficacy of the new algorithm, we analyzed the colon adenocarcinoma (COAD) and lung adenocarcinoma (LUAD) samples available at The Cancer Genome Atlas (TCGA). In the analysis of the COAD and LUAD samples, we identify epistatic gene pairs significantly mutated in tumor tissue with respect to normal tissue. We believe that further analysis of the gene pairs detected by our method will unveil new biological insights, enhancing a better description of the cancer mechanism.
Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias do Colo , Neoplasias Pulmonares , Humanos , Adenocarcinoma/genética , Epistasia Genética , Mutação , Neoplasias do Colo/genética , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Células GerminativasRESUMO
BACKGROUND: Over the last decade, the number of foreign citizens (FCs) in Spain has increased. There is no doubt that their health has become a relevant subject from the point of view of public healthcare. Our study aimed to describe hospital admission rates, diagnoses at hospital discharge, and mortality during hospital admissions in FCs from high-income countries (FCHICs), FCs from low-income countries (FCLICs), and autochthonous citizens (ACs). METHODS: A cross-sectional study was performed at two public hospitals in the city of Alicante (Spain) and its surrounding area. Utilization rates were estimated. Multivariate analysis adjusting for age and sex was performed on hospital admission rates, diagnoses at hospital discharge, service of admission, and mortality during hospital admission in FCHICs and FCLICs compared with ACs (adjusted odds ratio [AOR] with 95% confidence intervals [CI]). RESULTS: 42,839 patients ≥15 years were discharged from the hospitals. The utilization rate was lower in FCs than ACs, whose crude rate ratio was 0.676 (95% CI: 0.656-0.696). FCHICs had more risk of being diagnosed at discharge in the categories of the circulatory system (AOR: 1.55; 95% CI: 1.35-1.77), neoplasms (AOR: 1.21; 95% CI: 1.03-1.42), and injury and poisoning (AOR: 1.33; 95% CI: 1.11-1.58). FCLICs had more risk of being diagnosed in the categories of pregnancy, childbirth & puerperium (AOR: 1.33; 95% CI: 1.29-1.59), and injury and poisoning (AOR: 1.19; 95% CI: 1.03-1.36), and less risk in the mental disorder category (AOR: 0.32; 95% CI: 0.22-0.45). The length of hospitalization (in days) was lower in FCLICs (median: 3; IQR: 2-6) than both ACs (median: 4; IQR: 2-8) and FCHICs (median: 4; IQR: 2-8) (p < 0.001). The mortality rates on admission of ACs, FCHICs, and FCLICs were 4.2%, 3.3%, and 1.3%, respectively, but after adjusting for age and sex, the mortality rate risks were similar in FCHICs and FCLICs. CONCLUSION: First, FCs utilized hospitalization less when compared with ACs. Second, the hospitalization profile for FCHICs was similar to ACs, with more problems in the circulatory system, and the hospitalization profile for FCLICs was different compared with ACs, with more admissions for pregnancy, childbirth & puerperium.
Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos Transversais , Países Desenvolvidos/estatística & dados numéricos , Países em Desenvolvimento/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores Socioeconômicos , Espanha/epidemiologia , Adulto JovemRESUMO
UNLABELLED: To describe the characteristics of nonagenarians admitted to the surgical and medical divisions at a tertiary hospital and compare them with nonagenarians admitted to other hospital care services. METHODS: A retrospective study of all hospital discharge episodes via the registry of the Basic Minimum Data Set at the Hospital General Universitario de Alicante from January 2007 until December 2011. RESULTS: Of the 165,870 hospitalizations, 2461 (1.5%) were nonagenarians. The highest number of admitted nonagenarians was in the Division of General Internal Medicine (DGIM) (n=751), followed by the short stay unit (SSU) (n=633). The rate of nonagenarians per 100 admissions to the DGIM was 10.2, significantly higher than that of those admitted to the SSU (6.2) (p<0.001), the service of orthopedic and trauma surgery (2.2) (p<0.001), and other specialties. Females comprised 64.8% of the nonagenarians. Mortality was 17% for the nonagenarians admitted, while for those admitted to the DGIM it was 27.7%. Those hospitalized in the SSU had a lower risk of death during hospitalization (8.1%) (odds ratio [OR] 0.23, 95% confidence interval [CI] 0.16-0.32) and a greater risk of being admitted for diseases and disorders of the circulatory system (OR: 1.58, 95% CI: 1.22-2.05), particularly for heart failure and shock (OR: 1.82, 95% CI: 1.30-2.53), and being discharged with home hospitalization (OR: 8.05, 95% CI: 5.5-11.8). CONCLUSIONS: Nonagenarian patients represent a tenth of those admitted to the DGIM. The profile of nonagenarians admitted to the DGIM is different from other hospital services. Hospital mortality for nonagenarians admitted to the DGIM is high and superior to other hospital services.