RESUMO
Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Metilação de DNA , Detecção Precoce de Câncer , Biomarcadores , Medição de Risco , Helicobacter pylori/genética , Biomarcadores Tumorais/genética , Ilhas de CpG , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologiaRESUMO
Background The prognosis of hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT) is dismal after standard treatment with sorafenib. Hepatic arterial infusion chemotherapy (HAIC) has been suggested for patients with HCC and major PVTT. Purpose To compare the efficacy and safety of sorafenib plus 3cir-OFF HAIC versus sorafenib alone for advanced HCC with major PVTT. Materials and Methods This phase II trial recruited systemic treatment-naïve patients with HCC and major PVTT (portal vein invasion grade Vp3 [first branch] and Vp4 [main trunk]) between June 2017 and November 2019. Patients were randomly assigned (1:1 ratio) to receive sorafenib (400 mg twice daily) plus 3cir-OFF HAIC (35 mg/m2 oxaliplatin [hours 0-2] followed by 600 mg/m2 5-fluorouracil [hours 2-24], days 1-3) with a standardized percutaneous port catheter system or sorafenib alone (400 mg twice daily) every 4 weeks. The primary end point was overall survival (OS). The secondary end points were objective response rate, progression-free survival (PFS), and safety. OS and PFS were assessed using the Kaplan-Meier method and log-rank test. Results The intent-to-treat population included 64 patients, with 32 in each group. The median OS was 16.3 months (95% CI: 0.0, 35.5) with sorafenib plus HAIC and 6.5 months (95% CI: 4.4, 8.6) with sorafenib alone (hazard ratio [HR] = 0.28; 95% CI: 0.15, 0.53; P < .001). A higher objective response rate (41% [n = 13] vs 3% [n = 1], P < .001) and a longer median PFS (9.0 months vs 2.5 months; HR = 0.26; 95% CI: 0.15, 0.47; P < .001) were observed in the sorafenib plus HAIC group. Grade 3 or 4 adverse events were more frequent in the sorafenib plus HAIC group, including diarrhea (n = 7 [22%] vs n = 5 [16%]), hand-foot syndrome (n = 6 [19%] vs n = 2 [6%]), and thrombocytopenia (n = 7 [22%] vs n = 0). Conclusion Sorafenib plus 3cir-OFF hepatic arterial infusion chemotherapy may be a promising treatment in patients with hepatocellular carcinoma and major portal vein tumor thrombosis because of the improved survival and an acceptable safety profile. Clinical trial registration no. NCT03009461 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chung in this issue.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose Venosa , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Veia Porta , Sorafenibe/uso terapêutico , Resultado do Tratamento , Trombose Venosa/complicações , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológicoRESUMO
Melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin cancers. The incidence rates of all three types of skin cancers have increased in the past three decades. Light pigmentary traits have been recognized as one of the host risk factors for skin cancer, but findings on associations between eye colors and risk of skin cancers have been inconsistent.We performed a prospective analysis to examine the association between eye colors and risk of skin cancers using the Health Professionals Follow-up Study (HPFS). Cox proportional hazard models were applied to estimate relative risks (RRs) and their 95% confidence intervals (CIs). Effect modifications due to hair color and skin reaction to sun were also examined.The HPFS included 35,662 males. During a median follow-up of 19 years (1988-2012), 445 melanoma, 1123 SCC, and 7198 BCC cases were documented. Compared to those whose eye colors were dark or brown, participants with hazel/green/medium and blue/light colors had a 24% (RR = 1.24, 95% CI: 1.06-1.45) and a 19% (RR = 1.19, 95% CI: 1.01-1.41) higher risk of SCC, respectively. Similarly, a higher risk of BCC was observed in participants with hazel/green/medium eye colors (RR = 1.16, 95% CI: 1.09-1.23) and blue/light eye colors (RR = 1.17, 95% CI: 1.10-1.25). We did not find significant associations between eye color and risk of melanoma. Lighter eye color was associated with increased risks of SCC and BCC among those with dark hair colors (p for interaction ≤ 0.02).In conclusion, in this large prospective study of men, we found that light eye colors were associated with higher risks of SCC and BCC, but not melanoma. Further studies are needed to confirm this association in other populations.
Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/etiologia , Cor de Olho , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologiaRESUMO
BACKGROUND : The effectiveness of endoscopic screening on gastric cancer has not been widely investigated in China and the screening interval of repeated screening has not been determined. METHODS : In a population-based prospective study, we included 375,800 individuals, 14,670 of whom underwent endoscopic screening (2012-2018). We assessed the associations between endoscopic screening and risk of incident gastric cancer and gastric cancer-specific mortality, and examined changes in overall survival and disease-specific survival following screening. The optimal screening interval for repeated endoscopy for early detection of gastric cancer was explored. RESULTS : Ever receiving endoscopic screening significantly decreased the risk of invasive gastric cancer (age- and sex-adjusted relative risk [RR] 0.69, 95â% confidence interval [CI] 0.52-0.92) and gastric cancer-specific mortality (RR 0.33, 95â%CI 0.20-0.56), particularly for noncardia gastric cancer. Repeated screening strengthened the beneficial effect on invasive gastric cancer-specific mortality of one-time screening. Among invasive gastric cancers, screening-detected individuals had significantly better overall survival (RR 0.18, 95â%CI 0.13-0.25) and disease-specific survival (RR 0.18, 95â%CI 0.13-0.25) than unscreened individuals, particularly for those receiving repeated endoscopy. For individuals with intestinal metaplasia or low grade intraepithelial neoplasia, repeated endoscopy at an interval of <â2 years, particularly within 1 year, significantly enhanced the detection of early gastric cancer, compared with repeated screening after 2 years (P-trendâ=â0.02). CONCLUSION : Endoscopic screening prevented gastric cancer occurrence and death, and improved its prognosis in a population-based study. Repeated endoscopy enhanced the effectiveness. Screening interval should be based on gastric lesion severity.
Assuntos
Neoplasias Gástricas , Detecção Precoce de Câncer/métodos , Endoscopia Gastrointestinal , Humanos , Programas de Rastreamento/métodos , Estudos Prospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/prevenção & controleRESUMO
BACKGROUND: Some clinical trials found that cyclooxygenase-2 (COX-2) inhibitor use lowered the risk of skin cancer in high-risk groups. PATIENTS AND METHODS: To determine whether COX-2 inhibitor use is associated with lower risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, we analyzed COX-2 inhibitor use and risk of skin cancer based on three prospective cohort studies, the Nurses' Health Study (NHS), NHS II, and the Health Professionals Follow-up Study, including 153,882 participants. Multivariable hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association of COX-2 inhibitor use with risk of BCC, cSCC, and melanoma were estimated using Cox proportional hazards models. We pooled the results using a fixed effects model. RESULTS: 16,142 BCC, 1,973 cSCC, and 631 melanoma cases were documented. Ever vs. never use of COX-2 inhibitor was associated with a modestly increased risk of BCC (multivariable HR 1.09, 95 % CI 1.05-1.14). The hazard ratio was similar for cSCC (multivariable HR 1.12, 95 % CI 1.00-1.27) and melanoma (multivariable HR 1.10, 95 % CI 0.89-1.38), but was not statistically significant. CONCLUSIONS: Ever use of COX-2 inhibitor was not associated with a decreased skin cancer risk but was instead associated with a modest, increased risk of BCC.
Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma Basocelular/induzido quimicamente , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/prevenção & controle , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/prevenção & controle , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Seguimentos , Humanos , Estudos Prospectivos , Fatores de Risco , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/prevenção & controleRESUMO
BACKGROUND: Few studies have examined prognostic outcomes-associated molecular signatures other than overall survival (OS) for gastric cancer (GC). We aimed to identify DNA methylation biomarkers associated with multiple prognostic outcomes of GC in an epigenome-wide association study. METHODS: Based on the Cancer Genome Atlas (TCGA), DNA methylation loci associated with OS (n = 381), disease-specific survival (DSS, n = 372), and progression-free interval (PFI, n = 383) were discovered in training set subjects (false discovery rates < 0.05) randomly selected for each prognostic outcome and were then validated in remaining subjects (P-values < 0.05). Key CpGs simultaneously validated for OS, DSS, and PFI were further assessed for disease-free interval (DFI, n = 247). Gene set enrichment analyses were conducted to explore the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways simultaneously enriched for multiple GC prognostic outcomes. Methylation correlated blocks (MCBs) were identified for co-methylation patterns associated with GC prognosis. Based on key CpGs, risk score models were established to predict four prognostic outcomes. Spearman correlation analyses were performed between key CpG sites and their host gene mRNA expression. RESULTS: We newly identified DNA methylation of seven CpGs significantly associated with OS, DSS, and PFI of GC, including cg10399824 (GRK5), cg05275153 (RGS12), cg24406668 (MMP9), cg14719951(DSC3), and cg25117092 (MED12L), and two in intergenic regions (cg11348188 and cg11671115). Except cg10399824 and cg24406668, five of them were also significantly associated with DFI of GC. Neuroactive ligand-receptor interaction pathway was suggested to play a key role in the effect of DNA methylation on GC prognosis. Consistent with individual CpG-level association, three MCBs involving cg11671115, cg14719951, and cg24406668 were significantly associated with multiple prognostic outcomes of GC. Integrating key CpG loci, two risk score models performed well in predicting GC prognosis. Gene body DNA methylation of cg14719951, cg10399824, and cg25117092 was associated with their host gene expression, whereas no significant associations between their host gene expression and four clinical prognostic outcomes of GC were observed. CONCLUSIONS: We newly identified seven CpGs associated with OS, DSS, and PFI of GC, with five of them also associated with DFI, which might inform patient stratification in clinical practices.
Assuntos
Biomarcadores Tumorais/genética , Ilhas de CpG/genética , Metilação de DNA , Neoplasias Gástricas/mortalidade , Adolescente , Adulto , Conjuntos de Dados como Assunto , Epigênese Genética , Seguimentos , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico , Intervalo Livre de Progressão , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto JovemRESUMO
BACKGROUND: The risk of skin cancer associated with antihypertensive medication use is unclear, although thiazides have been implicated in regulatory safety warnings. We aimed to assess whether use of thiazides and other antihypertensives is associated with increased rates of keratinocyte carcinoma and melanoma. METHODS: We conducted a population-based inception cohort study using linked administrative health data from Ontario, 1998-2017. We matched adults aged ≥ 66 years with a first prescription for an antihypertensive medication (thiazides, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, ß-blockers) by age and sex to 2 unexposed adults who were prescribed a non-antihypertensive medication within 30 days of the index date. We evaluated each antihypertensive class in a separate cohort study. Our primary exposure was the cumulative dose within each class, standardized according to the World Health Organization's Defined Daily Dose. Outcomes were time to first keratinocyte carcinoma, advanced keratinocyte carcinoma and melanoma. RESULTS: The inception cohorts included a total of 302 634 adults prescribed an antihypertensive medication and 605 268 unexposed adults. Increasing thiazide exposure was associated with an increased rate of incident keratinocyte carcinoma (adjusted hazard ratios [HRs] per 1 Defined Annual Dose unit 1.08, 95% confidence interval [CI] 1.03-1.14), advanced keratinocyte carcinoma (adjusted HR 1.07, 95% CI 0.93-1.23) and melanoma (adjusted HR 1.34, 95% CI 1.01-1.78). We found no consistent evidence of association between other antihypertensive classes and keratinocyte carcinoma or melanoma. INTERPRETATION: Higher cumulative exposure to thiazides was associated with increased rates of incident skin cancer in people aged 66 years and older. Consideration of other antihypertensive treatments in patients at high risk of skin cancer may be warranted.
Assuntos
Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Carcinoma/epidemiologia , Hipertensão/tratamento farmacológico , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Ontário/epidemiologia , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Luz Solar/efeitos adversosRESUMO
BACKGROUND AND AIM: Dietary strategies that contribute to reducing incidence of Helicobacter pylori infection without negative side effects are highly desirable owing to worldwide bacterial prevalence and carcinogenesis potential. The aim of this study was to determine dosage effect of daily cranberry consumption on H. pylori suppression over time in infected adults to assess the potential of this complementary management strategy in a region with high gastric cancer risk and high prevalence of H. pylori infection. METHODS: This double-blind, randomized, placebo-controlled trial on 522 H. pylori-positive adults evaluated dose-response effects of proanthocyanidin-standardized cranberry juice, cranberry powder, or their placebos on suppression of H. pylori at 2 and 8 weeks by 13 C-urea breath testing and eradication at 45 days post-intervention. RESULTS: H. pylori-negative rates in placebo, low-proanthocyanidin, medium-proanthocyanidin, and high-proanthocyanidin cranberry juice groups at week 2 were 13.24%, 7.58%, 1.49%, and 13.85% and at week 8 were 7.35%, 7.58%, 4.48%, and 20.00%, respectively. Consumption of high-proanthocyanidin juice twice daily (44 mg proanthocyanidin/240-mL serving) for 8 weeks resulted in decreased H. pylori infection rate by 20% as compared with other dosages and placebo (P < 0.05). Percentage of H. pylori-negative participants increased from 2 to 8 weeks in subjects who consumed 44 mg proanthocyanidin/day juice once or twice daily, showing a statistically significant positive trend over time. Encapsulated cranberry powder doses were not significantly effective at either time point. Overall trial compliance was 94.25%. Cranberry juice and powder were well-tolerated. CONCLUSIONS: Twice-daily consumption of proanthocyanidin-standardized cranberry juice may help potentiate suppression of H. pylori infection. TRIAL REGISTRATION: ChiCTR1800017522, per WHO ICTRP.
Assuntos
Ingestão de Alimentos/fisiologia , Sucos de Frutas e Vegetais , Infecções por Helicobacter/dietoterapia , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori , Vaccinium macrocarpon , Adolescente , Adulto , Método Duplo-Cego , Feminino , Sucos de Frutas e Vegetais/análise , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Prevalência , Proantocianidinas/análise , Resultado do Tratamento , Vaccinium macrocarpon/química , Adulto JovemRESUMO
OBJECTIVE: Acute infectious laryngitis is commonly occurred among children. Our study sought to investigate the effect of inhaled budesonide on among children with acute infectious laryngitis. METHODS: A total of 92 children with acute infectious laryngitis were randomly allocated to either the study (46 cases, treated with inhaled budesonide) and control group (46 cases, treated with dexamethasone). The disappearance time of symptoms, therapeutic effect and adverse reactions were observed in the two groups. RESULTS: The therapeutic effect was significantly better in the study group than in the control group (97.83% vs 82.61%). After 3 days of treatment, the disappearance time of symptoms, such as hoarseness/barking cough, singing sound in the throat, three-concave sign and dyspnea in the study group was significantly less than that in the control group (P < 0.05). The levels of IL-4, IL-17, MMP-9, IL-33, IFN-γ and IgE in the two groups decreased, and evidently lower levels were found in the study group as compared to the control group (P < 0.05). CONCLUSION: Inhaled budesonide exerted obvious better effect in terms of reducing serum inflammatory factors and improving the quality of life with safety profile.
Assuntos
Budesonida/administração & dosagem , Mediadores da Inflamação/sangue , Laringite/tratamento farmacológico , Laringite/metabolismo , Qualidade de Vida , Doença Aguda , Administração por Inalação , Fatores Etários , Biomarcadores/sangue , Budesonida/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Interferon gama/sangue , Interleucina-17/sangue , Interleucina-33/sangue , Interleucina-4/sangue , Laringite/diagnóstico , Laringite/microbiologia , Masculino , Metaloproteinase 9 da Matriz/sangue , Resultado do TratamentoRESUMO
OBJECTIVE: Gastrointestinal microbiota may be involved in Helicobacter pylori-associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from H. pylori infection. DESIGN: Deep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment, relative to 49 H. pylori negative subjects. RESULTS: In H. pylori positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in H. pylori positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between Helicobacter and Fusobacterium, Neisseria, Prevotella, Veillonella, Rothia were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased Bifidobacterium after successful H. pylori eradication and more upregulated drug-resistant functional orthologs after failed treatment. CONCLUSION: H. pylori infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful H. pylori eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.
Assuntos
Disbiose , Gastrite Atrófica , Microbioma Gastrointestinal/genética , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Antibacterianos/uso terapêutico , Biópsia/métodos , Disbiose/diagnóstico , Disbiose/microbiologia , Fezes/microbiologia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Humanos , Masculino , Metaplasia/microbiologia , Metaplasia/patologia , Interações Microbianas , Pessoa de Meia-Idade , RNA Ribossômico 16S/isolamento & purificação , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: In prior studies, higher citrus consumption was associated with higher risk of cutaneous malignant melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). Furocoumarins, compounds with phototoxicity and photocarcinogenicity in citrus, may be responsible for the association. OBJECTIVES: The objective of the study was to investigate the association between furocoumarin intake and skin cancer risk. METHODS: A total of 47,453 men from the Health Professionals Follow-Up Study (HPFS) and 75,291 women from the Nurses' Health Study (NHS) with diet data collected every 2-4 y in the 2 prospective cohort studies were included. A furocoumarin food composition database for 7 common furocoumarins [bergaptol, psoralen, 8-methoxypsoralen, bergapten, 6',7'-dihydroxybergamottin (6'7'-DHB), epoxybergamottin, and bergamottin] was developed and used to calculate participants' cumulative average and energy-adjusted furocoumarin intake. Multivariate HRs and 95% CIs of the associations between furocoumarin intake and skin cancer risk were estimated using Cox proportional hazards models. Analyses were performed separately in each cohort as well as pooled using a fixed-effects model. RESULTS: Throughout follow-up (1984-2012 in the NHS and 1986-2012 in the HPFS), we identified 1593 melanoma, 4066 SCC, and 28,630 BCC cases. Higher intake of total furocoumarins was associated with an increased risk of BCC; the pooled HR comparing the top with the bottom quintile was 1.16 (95% CI: 1.11, 1.21; P-trend = 0.002). Higher intakes of bergaptol, bergapten, 6'7'-DHB, and bergamottin were also significantly associated with increased BCC risk. No significant associations were found between intake of total furocoumarins and the risks of SCC or melanoma. CONCLUSIONS: Intakes of total furocoumarins as well as some individual furocoumarins were associated with an increased risk of skin cancer, especially BCC, in 2 cohorts of US health professionals.
Assuntos
Citrus , Furocumarinas/administração & dosagem , Neoplasias Cutâneas/induzido quimicamente , Adulto , Feminino , Furocumarinas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/epidemiologia , Reino Unido , Estados Unidos/epidemiologiaRESUMO
Citrus products are rich sources of furocoumarins, a class of photoactive compounds. Certain furocoumarins combined with ultraviolet radiation can induce skin cancer. We examined the relationship between citrus consumption and cutaneous melanoma risk among 56,205 Caucasian postmenopausal women in the Women's Health Initiative. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma by citrus intake level. During a mean follow-up of 15.7 years, 956 incident melanoma cases were documented. In multivariable adjusted models, the HR (95% CI) for melanoma was 1.12 (0.91, 1.37) among the highest citrus consumers (1.5+ servings/day of fruit or juice) versus the lowest (<2 servings/week), 0.95 (0.76, 1.20) among the highest citrus fruit consumers (5+ servings/week) versus non-consumers, and was 1.13 (0.96, 1.32) for the highest citrus juice consumers (1+ servings/day) versus the lowest (<1 serving/week). In stratified analyses, an increased melanoma risk associated with citrus juice intake was observed among women who spent the most time outdoors in summer as adults; the HR for the highest versus lowest intake was 1.22 (1.02, 1.46) (p trend = 0.03). Further research is needed to explore the association of melanoma with citrus juices among women with high sun exposure.
Assuntos
Citrus , Melanoma/etiologia , Neoplasias Cutâneas/etiologia , Saúde da Mulher , Idoso , Feminino , Sucos de Frutas e Vegetais , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Melanoma Maligno CutâneoRESUMO
Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P < 1.0 × 10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P = 1.13 × 10-62) and CYP1B1 (P < 2.49 × 10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis.
Assuntos
Ilhas de CpG/genética , Neoplasias Pulmonares/genética , Fumar/efeitos adversos , Células A549/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores Tumorais/sangue , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Metilação de DNA/genética , Elementos Facilitadores Genéticos/genética , Epigênese Genética/genética , Epigenômica/métodos , Estudo de Associação Genômica Ampla , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Sequências Reguladoras de Ácido Nucleico/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fumar/genética , NicotianaRESUMO
BACKGROUND: It was unclear whether an increased number of common nevi (moles) predicts melanoma death. OBJECTIVE: We prospectively examined the association between number of common nevi and risk of melanoma death. METHODS: Our study used data from the Nurses' Health Study (n = 77,288 women) and Health Professionals Follow-up Study (n = 32,455 men). In 1986, participants were asked about the number of moles they had with a ≥3-mm diameter on the upper extremity, and we stratified their answers into 3 categories (none, 1-2, or ≥3) on the basis of data distribution. RESULTS: During follow-up (1986-2012), 2452 melanoma cases were pathologically confirmed; among these, we identified 196 deaths due to melanoma. Increased number of nevi was associated with melanoma death; the hazard ratio (HR) for ≥3 nevi compared with no nevi was 2.49 (95% confidence interval [CI] 1.50-4.12) for women and 3.97 (95% CI 2.54-6.22) for men. Among melanoma cases, increased number of nevi was associated with melanoma death in men (≥3 nevi, HR 1.89, 95% CI 1.17-3.05) but not in women. Similarly, the number of nevi was positively associated with Breslow thickness in men only (Ptrend = .01). LIMITATIONS: This is an epidemiologic study without examination into mechanisms. CONCLUSION: Increased number of cutaneous nevi was significantly associated with melanoma death. High nevus count might serve as an independent prognostic factor to predict the risk of melanoma death particularly among male melanoma patients.
Assuntos
Melanoma/mortalidade , Melanoma/patologia , Nevo/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nevo/epidemiologia , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Neoplasias Cutâneas/epidemiologia , Carga Tumoral , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Tetracycline is a photosensitising medication that increases skin vulnerability to UV-related damage. METHODS: We prospectively examined tetracycline use and risk of incident melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) based on 213 536 participants from the Nurses' Health Study (NHS), NHS2, and Health Professionals Follow-up Study. Information on ever use of tetracycline was asked via questionnaire. Diagnoses of melanoma and SCC were pathologically confirmed. RESULTS: Tetracycline use was associated with a modestly increased risk of BCC (ncase=36 377), with a pooled hazard ratio (HR) of 1.11 (95% confidence interval (CI)=1.02-1.21, P-trend=0.05 by duration of use). Tetracycline use was not significantly associated with melanoma (ncase=1831, HR=1.09, 95% CI=0.94-1.27) or SCC (ncase=3332, HR=1.04, 95% CI=0.91-1.18) risk overall. However, we observed positive interactions between tetracycline use and adulthood UV exposure on SCC risk (P-interaction=0.05). CONCLUSION: Tetracycline use was associated with a modestly increased risk of BCC, but was not associated with melanoma or SCC.
Assuntos
Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias Cutâneas/epidemiologia , Tetraciclina/administração & dosagem , Adulto , Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Feminino , Humanos , Incidência , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Red and processed meat consumption has been associated with increased risk for several cancers, but the association with cutaneous melanoma risk has been inconclusive. OBJECTIVE: To investigate the association between red and processed meat intake and melanoma risk. METHODS: Dietary information was assessed by using food frequency questionnaires in 2 prospective cohorts: 75,263 women from the Nurses' Health Study (1984-2010) and 48,523 men from the Health Professionals Follow-up Study (1986-2010). Melanoma cases were confirmed by reviewing pathology records. Pooled multivariable hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models. RESULTS: A total of 679 female and 639 male melanoma cases were documented during follow-up. Red and processed meat intake was inversely associated with melanoma risk (P = .002 for trend); the pooled hazard ratios (95% confidence intervals) of the 2 cohorts were 1.00 (reference), 1.00 (0.87-1.14), 0.98 (0.86-1.13), 0.89 (0.77-1.02), and 0.81 (0.70-0.95) for increasing quintiles of intake. LIMITATIONS: Findings might have limited generalizability, considering that the cohorts were limited to white health professionals. CONCLUSION: Red and processed meat intake was inversely associated with melanoma risk in these 2 cohorts.
Assuntos
Dieta/efeitos adversos , Produtos da Carne/efeitos adversos , Melanoma/epidemiologia , Carne Vermelha/efeitos adversos , Neoplasias Cutâneas/epidemiologia , População Branca/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Melanoma/etnologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Neoplasias Cutâneas/etnologia , Inquéritos e Questionários , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Statins are among the most commonly used medications in the United States, and statin use is associated with increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). However, previous studies are limited by lack of adjustment for important confounders. OBJECTIVE: Examine the relation between statins and skin cancer risk in the Nurses' Health Study and Health Professionals Follow-up Study. METHODS: Cox proportional hazards regression was used to evaluate associations. RESULTS: During follow-up (2000-2010), we documented 10,201 BCC, 1393 SCC, and 333 melanoma cases. History of high cholesterol level was not associated with risk of BCC (pooled multivariable-adjusted hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.09), SCC (HR, 0.95; 95% CI, 0.85-1.06), or melanoma (HR, 0.87; 95% CI, 0.64-1.19). Statin use was not associated with risk of BCC (HR, 1.04; 95% CI, 0.99-1.09]), SCC (HR, 1.08; 95% CI, 0.94-1.24), or melanoma (HR, 1.04; 95% CI, 0.78-1.38). There was a trend toward higher BCC risk with longer duration of statin use in men (P trend = .003) but not in women (P trend = .86). LIMITATIONS: Lack of treatment data. CONCLUSION: History of high cholesterol level was not associated with skin cancer risk. Longer duration of statin use was associated with a trend toward higher BCC risk in men.
Assuntos
Carcinoma Basocelular/induzido quimicamente , Carcinoma Basocelular/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de RiscoRESUMO
The expression of fibroblast growth factor 9 (FGF9) recombinant fusion protein in Carthamus tinctorius was used to identify its effect on hair regrowth and wound repair system in mice, providing a basis for C. tinctorius as a plant bioreactor, and establishing a foundation for commercial applications of FGF9 fusion protein in hair regrowth and wound repair. The identified pOTBar-oleosin-rhFGF9 plasmid was transformed into Agrobacterium tumefaciens EHA105 by freeze-thaw method, and the oleosin-rhFGF9 gene was transformed into safflower leaves by A. tumefaciens mediated method. Transgenic safflower seedlings were then obtained by tissue culture. After basta screening, transgenic T3 safflower seeds were obtained by grafting method, PCR verification and propagation. The expression of oleosin-rhFGF9 was detected by Western blot, and the content of oleosin-rhFGF9 fusion protein was 0.09% by using ELISA quantitative method. It was observed that 60 µg·L⻹ transgenic safflower oil had better effect on promoting NIH/3T3 cells proliferation in a certain dose-dependent manner. Sixty C57BL/6 mice were used to establish alopecia model and wound model respectively, and then were randomly divided into control group (treated with PBS or saline), negative group (treated with wild type safflower seed oil bodies, 60 g·L⻹), positive group (treated with FGF9, 0.054 g·L⻹), low dose group (treated with transgenic safflower oil bodies, 10 g·L⻹) and high dose group (treated with transgenic safflower oil bodies, 60 g·L⻹). The skin of all above-mentioned mice models were coated with soft adhesive manner every other day, 100 µL/time. After 15 days, the mice skin was cut and embedded for histological analysis. The hair regrowth experimental results showed that the hair of mice grew well, and the mice in high dose group had bushy hair, with significant effect on regeneration hair number as compared with the positive group. The healing was obvious in wound experiment, with significant healing effect in positive group, high dose group and low dose group as compared to blank control group. Furthermore, high dose group remarkably showed a better and higher healing effect than the positive group at day 5. Oleosin-rhFGF9 was successfully transformed into safflower, and T3 transgenic safflower oil bodies expressed oleosin-rhFGF9 fusion protein were obtained, with the role of promoting hair regeneration and wound repair in mice.
Assuntos
Carthamus tinctorius , Animais , Fator 9 de Crescimento de Fibroblastos , Cabelo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Regeneração , SementesRESUMO
A recent clinical trial found a protective role of niacinamide, a derivative of niacin, against skin cancer recurrence. However, there is no epidemiologic study to assess the association between niacin intake and risk of skin cancer [basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma]. We prospectively evaluated whether total, dietary and supplemental niacin intake was associated with skin cancer risk based on 72,308 women in the Nurses' Health Study (1984-2010) and 41,808 men in the Health Professionals Follow-up Study (1986-2010). Niacin intake was assessed every 2 to 4 years during follow-up and cumulative averaged intake. Cox proportional hazard models were used to compute the hazard ratios (HR) and 95% confidence intervals (CI) and cohort-specific results were pooled using a random-effects model. During the follow-up, we documented 23,256 BCC, 2,530 SCC and 887 melanoma cases. Total niacin intake was inversely associated with SCC risk; the pooled HR for top vs. bottom quintiles was 0.84 (95% CI = 0.74-0.95; ptrend = 0.08). However, there were a marginally positive association between total niacin intake and BCC risk; the pooled HR for top versus bottom quintiles was 1.05 (95% CI = 1.01-1.10; ptrend < 0.01). Higher total niacin intake was also marginally positively associated with melanoma risk in men, but not in women. The results were similar in stratified analyses according to sun exposure related factors and by body location of melanoma and SCC. Our study supports a potential beneficial role of niacin intake in relation to SCC but not of BCC or melanoma.
Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Melanoma/epidemiologia , Niacina/uso terapêutico , Neoplasias Cutâneas/epidemiologia , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Dieta , Feminino , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Niacina/efeitos adversos , Modelos de Riscos Proporcionais , Fatores de Risco , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Estados Unidos/epidemiologiaRESUMO
The relationship between smoking and rosacea is poorly understood. We aimed to conduct the first cohort study to determine the association between smoking and risk of incident rosacea. We included 95,809 women from Nurses' Health Study II (1991-2005). Information on smoking was collected biennially during follow-up. Information on history of clinician-diagnosed rosacea and year of diagnosis was collected in 2005. We used Cox proportional hazards models to estimate age- and multivariable-adjusted hazard ratios and 95% confidence intervals for the association between different measures of smoking and risk of rosacea. During follow-up, we identified 5,462 incident cases of rosacea. Compared with never smoking, we observed an increased risk of rosacea associated with past smoking (multivariable-adjusted hazard ratio = 1.09, 95% confidence interval: 1.03, 1.16) but a decreased risk associated with current smoking (hazard ratio = 0.65, 95% confidence interval: 0.58, 0.72). We further found that increasing pack-years of smoking was associated with an elevated risk of rosacea among past smokers (P for trend = 0.003) and with a decreased risk of rosacea among current smokers (P for trend < 0.0001). The risk of rosacea was significantly increased within 3-9 years since smoking cessation, and the significant association persisted among past smokers who had quit over 30 years before.