Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
1.
Lung Cancer ; 152: 58-65, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33352384

RESUMO

INTRODUCTION: The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC). METHODS: Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses. RESULTS: Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; pinteraction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (pinteraction = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (pinteraction<0.001) and obese categories (pinteraction = 0.004) relative to the normal-BMI category, when compared to male ever-smokers. CONCLUSION: Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships.

2.
Cancer Cell ; 38(5): 598-601, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33038939

RESUMO

During the COVID-19 pandemic, research on "cytokine storms" has been reinvigorated in the field of infectious disease, but it also has particular relevance to cancer research. Interleukin-6 (IL-6) has emerged as a key component of the immune response to SARS-CoV-2, such that the repurposing of anti-IL-6 therapeutics for COVID-19 is now a major line of investigation, with several ongoing clinical trials. We lay a framework for understanding the role of IL-6 in the context of cancer research and COVID-19 and suggest how lessons learned from cancer research may impact SARS-CoV-2 research and vice versa.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/complicações , Citocinas/sangue , Inflamação/etiologia , Neoplasias/imunologia , Pneumonia Viral/complicações , Índice de Gravidade de Doença , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citocinas/imunologia , Humanos , Inflamação/patologia , Neoplasias/sangue , Neoplasias/virologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia
3.
J Thorac Oncol ; 15(12): 1880-1892, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32931935

RESUMO

INTRODUCTION: Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States, especially among men. Although significant progress has been made profiling the genomic makeup of lung cancer in EAs, AAs continue to be underrepresented. Our objective was to chart the genome-wide landscape of somatic mutations in lung cancer tumors from AAs. METHODS: In this study, we used the whole-exome sequencing of 82 tumor and noninvolved tissue pairs from AAs. Patients were selected from an ongoing case-control study conducted by the National Cancer Institute and the University of Maryland. RESULTS: Among all samples, we identified 178 significantly mutated genes (p < 0.05), five of which passed the threshold for false discovery rate (p < 0.1). In lung adenocarcinoma (LUAD) tumors, mutation rates in STK11 (p = 0.05) and RB1 (p = 0.008) were significantly higher in AA LUAD tumors (25% and 13%, respectively) compared with The Cancer Genome Atlas EA samples (14% and 4%, respectively). In squamous cell carcinomas, mutation rates in STK11 (p = 0.002) were significantly higher among AA (8%) than EA tumors from The Cancer Genome Atlas (1%). Integrated somatic mutation data with CIBERSORT (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts) data analysis revealed LUAD tumors from AAs carrying STK11 mutations have decreased interferon signaling. CONCLUSIONS: Although a considerable degree of the somatic mutation landscape is shared between EAs and AAs, discrete differences in mutation frequency in potentially important oncogenes and tumor suppressors exist. A better understanding of the molecular basis of lung cancer in AA patients and leveraging this information to guide clinical interventions may help reduce disparities.

6.
Nat Commun ; 10(1): 5735, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31844068

RESUMO

Reducing or eliminating persistent disparities in lung cancer incidence and survival has been challenging because our current understanding of lung cancer biology is derived primarily from populations of European descent. Here we show results from a targeted sequencing panel using NCI-MD Case Control Study patient samples and reveal a significantly higher prevalence of PTPRT and JAK2 mutations in lung adenocarcinomas among African Americans compared with European Americans. This increase in mutation frequency was validated with independent WES data from the NCI-MD Case Control Study and TCGA. We find that patients carrying these mutations have a concomitant increase in IL-6/STAT3 signaling and miR-21 expression. Together, these findings suggest the identification of these potentially actionable mutations could have clinical significance for targeted therapy and the enrollment of minority populations in clinical trials.


Assuntos
Adenocarcinoma de Pulmão/genética , Afro-Americanos/genética , Janus Quinase 2/genética , Neoplasias Pulmonares/genética , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Idoso , Estudos de Casos e Controles , Análise Mutacional de DNA , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Disparidades nos Níveis de Saúde , Humanos , Interleucina-6/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Mutação , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/genética
7.
Cancer Causes Control ; 30(11): 1259-1268, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31468279

RESUMO

PURPOSE: African Americans, especially men, have a higher incidence of lung cancer compared with all other racial and ethnic groups in the US. Self-reported race is frequently used in genomic research studies to capture an individual's race or ethnicity. However, it is clear from studies of genetic admixture that human genetic variation does not segregate into the same biologically discrete categories as socially defined categories of race. Previous studies have suggested that the degree of West African ancestry among African Americans can contribute to cancer risk in this population, though few studies have addressed this question in lung cancer. METHODS: Using a genetic ancestry panel of 100 SNPs, we estimated West African, European, and Native American ancestry in 1,407 self-described African Americans and 2,413 European Americans. RESULTS: We found that increasing West African ancestry was associated with increased risk of lung cancer among African American men (ORQ5 vs Q1 = 2.55 (1.45-4.48), p = 0.001), while no association was observed in African American women (ORQ5 vs Q1 = 0.90 (0.51-1.59), p = 0.56). This relationship diminished following adjustment for income and education. CONCLUSIONS: Genetic ancestry is not a major contributor to lung cancer risk or survival disparities.


Assuntos
Grupo com Ancestrais do Continente Africano , Neoplasias Pulmonares , África Ocidental , Grupo com Ancestrais do Continente Africano/etnologia , Grupo com Ancestrais do Continente Africano/genética , Idoso , Feminino , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco
8.
J Thorac Oncol ; 14(9): 1594-1607, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31163278

RESUMO

INTRODUCTION: The relationships between morbid obesity, changes in body mass index (BMI) before cancer diagnosis, and lung cancer outcomes by histology (SCLC and NSCLC) have not been well studied. METHODS: Individual level data analysis was performed on 25,430 patients with NSCLC and 2787 patients with SCLC from 16 studies of the International Lung Cancer Consortium evaluating the association between various BMI variables and lung cancer overall survival, reported as adjusted hazard ratios (aHRs) from Cox proportional hazards models and adjusted penalized smoothing spline plots. RESULTS: Overall survival of NSCLC had putative U-shaped hazard ratio relationships with BMI based on spline plots: being underweight (BMI < 18.5 kg/m2; aHR = 1.56; 95% confidence interval [CI]:1.43-1.70) or morbidly overweight (BMI > 40 kg/m2; aHR = 1.09; 95% CI: 0.95-1.26) at the time of diagnosis was associated with worse stage-specific prognosis, whereas being overweight (25 kg/m2 ≤ BMI < 30 kg/m2; aHR = 0.89; 95% CI: 0.85-0.95) or obese (30 kg/m2 ≤ BMI ≤ 40 kg/m2; aHR = 0.86; 95% CI: 0.82-0.91) was associated with improved survival. Although not significant, a similar pattern was seen with SCLC. Compared with an increased or stable BMI from the period between young adulthood until date of diagnosis, a decreased BMI was associated with worse outcomes in NSCLC (aHR = 1.24; 95% CI: 1.2-1.3) and SCLC patients (aHR=1.26 (95% CI: 1.0-1.6). Decreased BMI was consistently associated with worse outcome, across clinicodemographic subsets. CONCLUSIONS: Both being underweight or morbidly obese at time of diagnosis is associated with lower stage-specific survival in independent assessments of NSCLC and SCLC patients. In addition, a decrease in BMI at lung cancer diagnosis relative to early adulthood is a consistent marker of poor survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/mortalidade , Análise de Sobrevida , Adulto Jovem
9.
J Thorac Oncol ; 14(7): 1192-1203, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30953795

RESUMO

INTRODUCTION: Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States. We and others have previously shown a relationship between immune and inflammation proteins with lung cancer in EAs. Our aim was to investigate the etiologic relationship between inflammation and lung cancer in AAs. METHODS: We adopted a two-stage, independent study design (discovery cases, n = 316; control cases, n = 509) (validation cases, n = 399; control cases, n = 400 controls) and measured 30 inflammation proteins in blood using Meso Scale Discovery V- PLEX multiplex assays. RESULTS: We identified and validated 10 proteins associated with lung cancer in AAS, some that were common between EAs and AAs (C-reactive proteins [OR: 2.90; 95% confidence interval (CI): 1.99-4.22], interferon γ [OR: 1.55; 95% CI: 1.10-2.19], interleukin 6 [OR: 6.28; 95% CI: 4.10-9.63], interleukin 8 [OR: 2.76; 95% CI: 1.92-3.98]) and some that are only observed among AAs (interleukin 10 [OR: 1.69; 95% CI: 1.20-2.38], interleukin 15 [OR: 2.83; 95% CI: 1.96-4.07], interferon gamma-induced protein 10 [OR: 1.54; 95% CI: 1.09-2.18], monocyte chemotactic protein-4 [OR: 0.54; 95% CI: 0.38-0.76], macrophage inflammatory protein-1 alpha [OR: 1.57; 95% CI: 1.12-2.21], and tumor necrosis factor ß [OR: 0.52; 95% CI: 0.37-0.74]). We did not find evidence that either menthol cigarette smoking or global genetic ancestry drove these population differences. CONCLUSIONS: Our results highlight a distinct inflammation profile associated with lung cancer in AAs compared with EAs. These data provide new insight into the etiology of lung cancer in AAs. Further work is needed to understand what drives this relationship with lung cancer and whether these proteins have utility in the setting of early diagnosis.


Assuntos
Afro-Americanos/estatística & dados numéricos , Biomarcadores/sangue , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Mediadores da Inflamação/sangue , Inflamação/complicações , Neoplasias Pulmonares/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
10.
J Thorac Oncol ; 14(8): 1360-1369, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31009812

RESUMO

INTRODUCTION: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. METHODS: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. RESULTS: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 × 10-16), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 × 10-16), and rs4975616 (OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 × 10-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. CONCLUSIONS: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.


Assuntos
Cromossomos Humanos Par 5 , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Telomerase/genética , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla/métodos , Técnicas de Genotipagem/métodos , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
12.
Cancer Epidemiol Biomarkers Prev ; 28(1): 110-118, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30297515

RESUMO

BACKGROUND: Previously, we observed a strong relationship between circulating serum inflammation proteins in relation to lung cancer diagnosis and risk, both in case-control and prospective cohorts. Low-dose computed tomography (LDCT) screening has a high prevalence of false-positive nodules, thus companion noninvasive biomarkers that can distinguish between benign and malignant nodules could have clinical utility and positive impact on patient outcomes. METHODS: We conducted a nested case-control study within the National Lung Screening Trial. Concentrations of 30 inflammation proteins were measured on plasma samples of 262 cases and 528 controls using a highly sensitive and analytically validated electrochemiluminescence V-PLEX immunoassay. RESULTS: Comparing the fourth quartile with the first quartile, we found increased IFNγ and IL12/IL23p40 associated with increased odds of a lung cancer diagnosis [OR 1.89, 95% confidence intervals (CI), 1.16-3.09; OR 2.49, 95% CI, 1.46-4.23, respectively]. Confirming our previous observations, we also detected a relationship between increased IL6, IL8, and C-reactive protein (CRP) with lung cancer diagnosis. These relationships were significant after adjustment for age, gender, race, smoking, body mass index (BMI), family history of lung cancer, and previous diagnoses of inflammatory conditions. However, none of these proteins could distinguish between a benign and malignant lung nodule (IL6: OR 1.25, 95% CI, 0.59-2.64; IL8: OR 1.40, 95% CI, 0.70-2.81; CRP: OR 0.98, 95% CI, 0.45-2.12). CONCLUSIONS: We have discovered new associations for IFNγ and IL12/IL23p40 with lung cancer but have no evidence that these proteins can distinguish between benign and malignant lung nodules. IMPACT: Circulating inflammation proteins are unlikely to have utility as companion LDCT biomarkers.


Assuntos
Proteína C-Reativa/análise , Citocinas/sangue , Inflamação , Neoplasias Pulmonares/sangue , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória
14.
Commun Biol ; 1: 191, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30456312

RESUMO

Sexually transmitted infections can reach the prostate gland where their harmful effects are mediated by innate immunity, including interferons. Humans are polymorphic for the germline dinucleotide variant, rs368234815-TT/ΔG, in the IFNL4 gene encoding interferon λ4. Since the IFNL4-ΔG allele has been linked to impaired viral clearance, we hypothesized that potential exposure to sexually transmitted pathogens, as assessed by the number of lifetime sexual partners, may increase prostate cancer risk in an IFNL4-ΔG-dependent manner. Accordingly, we find that men with 10 or more sexual partners and at least one copy of IFNL4-ΔG have a significantly increased risk of prostate cancer while those with the same number of partners but lacking IFNL4-ΔG do not. Moreover, a test for effect modification shows a positive interaction between the number of lifetime partners and IFNL4-ΔG in the development of aggressive prostate cancer. Based on these findings, we conclude that a gene-environment interaction between IFNL4-ΔG and sexual activity may increase the risk of prostate cancer.

15.
J Appl Lab Med ; 3(2): 166-177, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30370398

RESUMO

Background: There is an urgent need for a companion assay to work with mesothelin-targeted therapeutic agents and for noninvasive and accurate prognostication of malignant mesothelioma (MM) patients. We report the development and validation of a blood-based assay for megakaryocyte potentiating factor (MPF) and the evaluation of its effectiveness for prognosis in MM and lung cancer patients. Methods: Using electrochemiluminescence technology, we developed a sensitive MPF assay and performed both analytical and clinical validations. Further, the effectiveness of the MPF assay in predicting prognosis was evaluated for 95 MM and 272 lung cancer patients. Results: We performed comprehensive analytical and clinical validation, including precision and accuracy, interference, preanalytical variables, sensitivity, and specificity for mesothelioma. In MM patients, increased serum MPF is a predictor of poor survival with a hazard ratio (HR) = 2.46 (log-rank P = 0.003; n = 95). In refractory MM patients, increased MPF is a strong predictor of poor outcome with an HR = 6.12 (log-rank P = 0.0007; n = 57). In a lung cancer patient cohort, increased MPF is a predictor of poor survival, with an HR = 1.57 (log-rank P = 0.003; n = 272). Conclusions: The MPF assay has robust technical characteristics, with strong analytic and clinical validation. Clinical studies indicate that increased serum MPF is a predictor of poor survival for MM patients, throughout the course of the disease. Increased MPF is also associated with poor overall survival for patients with newly diagnosed lung cancer.


Assuntos
Proteínas Ligadas por GPI/sangue , Neoplasias Pulmonares , Mesotelioma , Biomarcadores Tumorais/sangue , Estudos de Coortes , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Mesotelioma/sangue , Mesotelioma/diagnóstico , Prognóstico , Sensibilidade e Especificidade , Análise de Sobrevida
16.
Cancer Epidemiol Biomarkers Prev ; 27(12): 1518-1526, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30171037

RESUMO

BACKGROUND: African Americans (AA) experience higher incidence and mortality of lung cancer as compared with European Americans (EA). Inflammation is associated with lung cancer, many aspects of which differ between AA and EA. We investigated whether use, frequency, and duration of the anti-inflammatory drug aspirin were associated with lung cancer risk and survival, separately among AA and EA populations. METHODS: Using data from the Maryland Non-Small Cell Lung Cancer (NSCLC) Case-Control Study (1,220 cases [404 AA and 816 EA] and 1,634 controls [1,004 EA and 630 AA]), we estimated the adjusted odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) of the associations between aspirin use and NSCLC risk and survival, respectively. RESULTS: Any aspirin use (OR: 0.66; 95% CI, 0.49-0.89), daily use of ≥ 1 tablet (OR: 0.68; 95% CI, 0.50-0.90), and use for ≥ 3 years (OR: 0.61; 95% CI, 0.44-0.85) was associated with lower NSCLC risk only among men, even after adjustment for covariates including body mass index and global genetic ancestry. These variables were also associated with improved survival, but only among AA (HR: 0.64; 95% CI, 0.46-0.91; HR: 0.61; 95% CI, 0.42-0.90; and HR: 0.60; 95% CI, 0.39-0.92, respectively). Tylenol and other NSAIDs were either associated with elevated or no NSCLC risk. CONCLUSIONS: Aspirin use is associated with lower risk of NSCLC among men and improved survival among AA. IMPACT: Preventive regular aspirin use could be considered among men and AA.


Assuntos
Aspirina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/induzido quimicamente , Neoplasias Pulmonares/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Casos e Controles , Grupos de Populações Continentais , Grupos Étnicos , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
17.
Genome Biol ; 19(1): 123, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30143034

RESUMO

BACKGROUND: Lung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort. RESULTS: Overall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas. CONCLUSIONS: The results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection.


Assuntos
Neoplasias Pulmonares/genética , Neoplasias Pulmonares/microbiologia , Microbiota/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Biodiversidade , Comamonadaceae/classificação , Comamonadaceae/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Neoplasias de Células Escamosas/genética , Neoplasias de Células Escamosas/microbiologia , Proteobactérias/metabolismo , Reprodutibilidade dos Testes , Fumantes , Proteína Supressora de Tumor p53/metabolismo
18.
Transl Lung Cancer Res ; 7(Suppl 2): S123-S126, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29782564
19.
Cancer Med ; 7(6): 2764-2775, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29726119

RESUMO

Vitamin D is an essential micronutrient required for normal physiological function and recognized for its role regulating calcium metabolism. Recent work is beginning to emerge demonstrating a role for vitamin D in chronic illnesses, such as cancer. Circulating serum levels of 25(OH)D2/3 were quantitatively measured using sensitive ultraperformance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) in 406 lung cancer cases and 437 population controls, while 1,25(OH)2 D2/3 levels were measured in a subset of 90 cases and 104 controls using the same method, from the NCI-MD case-control cohort. 25(OH)D3 levels were inversely associated with lung cancer status across quartiles (Q2 vs. Q1: ORadjusted  = 0.5, 95% CI = 0.3-0.8; Q3 vs. Q1: ORadjusted  = 0.5, 95% CI = 0.3-0.8; Q4 vs. Q1: ORadjusted  = 0.5, 95% CI = 0.2-0.9; Ptrend  = 0.004). Levels of 1,25(OH)2 D3 were also inversely associated with lung cancer status (Q2 vs. Q1: ORadjusted  = 0.2, 95% CI = 0.03-0.7; Q3 vs. Q1: ORadjusted  = 0.1, 95% CI = 0.01-0.4; Q4 vs. Q1: ORadjusted  = 0.04, 95% CI = 0.01-0.3; Ptrend <0.0001). Although the observed trends were similar for the 25(OH)D2 (Ptrend  = 0.08), no significant associations were seen between vitamin D2 and lung cancer status. Additionally, genotyping of 296 SNPs in the same subjects resulted in findings that 27 SNPs, predominantly in CYP24A1 and VDR genes, were significantly associated with lung cancer status, affected mRNA expression, and modulated vitamin D levels. These findings suggest a protective role for vitamin D3 in lung cancer, with similar trends but insignificant findings for D2 . Vitamin D3 levels appeared to be modulated by genetic variation in CYP24A1 and VDR genes. Additional research to illuminate the mechanism(s) through which vitamin D exacerbates effects against lung carcinogenesis is warranted.


Assuntos
Colecalciferol/metabolismo , Variação Genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Idoso , Estudos de Casos e Controles , Colecalciferol/sangue , Cromatografia Líquida , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/sangue , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Espectrometria de Massas em Tandem , Vitamina D3 24-Hidroxilase/genética
20.
Carcinogenesis ; 39(6): 741-751, 2018 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-29547922

RESUMO

Compared with all other racial and ethnic groups in the United States, African Americans are disproportionally affected by lung cancer, both in terms of incidence and survival. It is likely that smoking, as the main etiological factor associated with lung cancer, contributes to these disparities, but the precise mechanism is still unclear. This paper seeks to explore the history of lung cancer disparities and review to the literature regarding the various factors that contribute to them.


Assuntos
Neoplasias Pulmonares/etiologia , Afro-Americanos , Grupos Étnicos , Disparidades em Assistência à Saúde , Humanos , Incidência , Fumar/efeitos adversos , Estados Unidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...