RESUMO
Evidence is required to evaluate the effectiveness of population-level endoscopic screening for esophageal cancer (EC). In this study, 5,632 permanent residents aged 25-65 years from 6 villages in Hua County, Henan Province, China, were defined as the screening cohort and were offered intensive endoscopic screening. Residents of all 914 remaining villages in Hua County were included as the control cohort, and age-sex standardization was used to calculate the expected numbers of EC and upper gastrointestinal (GI) tract cancer cases and deaths in the screening cohort. The effectiveness of screening was assessed by comparing observed numbers of cases and deaths with expected numbers after 9-year follow-up of these screened subjects (2007-2016). In the screening cohort, 23 upper GI cancers (including 16 ECs) and 10 upper GI cancer deaths (including 5 EC deaths) were identified, and 47% (standardized incidence ratio = 0.53, 95% confidence interval (CI): 0.33, 0.87) and 66% (standardized mortality ratio = 0.34, 95% CI: 0.14, 0.81) reductions in cumulative EC incidence and mortality were found. For upper GI cancers, incidence and mortality were lowered by 43% (standardized incidence ratio = 0.57, 95% CI: 0.38, 0.86) and 53% (standardized mortality ratio = 0.47, 95% CI: 0.25, 0.88), respectively. This study showed that upper GI tract endoscopy is an effective population-level screening test for EC in high-risk regions.
Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Endoscopia Gastrointestinal/estatística & dados numéricos , Neoplasias Esofágicas/epidemiologia , Adulto , Idoso , China/epidemiologia , Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/prevenção & controle , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
Results of previous serologic studies on the association of human papillomavirus (HPV) with esophageal squamous cell carcinoma (ESCC) have been inconsistent. From 2007 to 2010, the authors collected blood samples and relevant demographic data from 1435 patients with ESCC and 2071 age- and sex-matched normal controls from Anyang, China. HPV-16, 18 and 57 E7 antibodies were evaluated with the glutathione-S-transferase capture ELISA. The proportions of subjects who were positive for antibodies against these three HPV antigens in the case group were all significantly higher than those in the control group. In multivariate analysis, the presence of HPV-16 E7 antibody was associated with an increased risk of ESCC [odds ratio (OR) = 3.6, 95% confidence interval (CI): 2.5-5.0], whereas the presence of HPV-18 (OR = 1.1, 95% CI: 0.7-1.7) and HPV-57 (OR = 1.3, 95% CI: 0.9-1.9) antibodies were not significant after adjustment for HPV-16. In multiple cutoff value analysis, the lowest OR for HPV-16 was obtained with the standard cut point mean + 3 SD. This study provides serological evidence in support of HPV-16 infection playing a role in the occurrence of ESCC in a high-incidence area of China.
Assuntos
Alphapapillomavirus/isolamento & purificação , Carcinoma de Células Escamosas/virologia , Neoplasias Esofágicas/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Nine novel human papillomavirus (HPV) types were isolated from healthy skin of individuals in rural Anyang, China. All of these isolates belong to the genus Gammapapillomavirus. These data will provide us with useful information for a better understanding of PV evolution and the relationship of PV with the host.
Assuntos
DNA Viral/química , DNA Viral/genética , Gammapapillomavirus/genética , Genoma Viral , China , Gammapapillomavirus/classificação , Gammapapillomavirus/isolamento & purificação , Genótipo , Humanos , Dados de Sequência Molecular , População Rural , Análise de Sequência de DNA , Pele/virologiaRESUMO
The genomic characteristics during the carcinogenic process of esophageal squamous cell carcinoma (ESCC) remain largely unknown. We report here the genomic characteristics of 106 esophageal tissues of various stages from a population-based screening cohort in China ("Endoscopic Screening for Esophageal Cancer in China" trial) and 57 ESCC tissues from a local hospital. A significant increase in somatic mutation and copy number alterations is observed in the non-dysplastic Lugol unstaining lesions (ND-LULs). Extensive clonal expansion has emerged in the ND-LULs to an extent similar to that in higher-stage lesions. The burden of genomic alterations correlates with the size of LULs in the ND-LULs. 8-year follow-up shows that ND-LULs harbor an increased risk of progression to ESCC (adjusted IRR6-10 mm vs. none = 4.66, adjusted IRR>10 mm vs. none = 40.70), and the risk is correlated with LUL size for both non-dysplastic and dysplastic lesions. Lugol unstaining can be the initial stage in the carcinogenic process of ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Genômica , Estudos Epidemiológicos , Carcinógenos , Coloração e RotulagemRESUMO
Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors. Here, we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals. In blood, sperm, and muscle cells, we resolved three common types of mutational signatures. Signatures A and B represent clock-like mutational processes, and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles. Notably, signature C, characterized by C>T transitions at GpCpN sites, tends to be a feature of diverse normal tissues. Mutations of this type are likely to occur early during embryonic development, supported by their relatively high allelic frequencies, presence in multiple tissues, and decrease in occurrence with age. Almost none of the public datasets for tumors feature this signature, except for 19.6% of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Moreover, the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α. Thus, embryonic hypoxia may explain this novel signature across multiple normal tissues. Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites; and individuals' genetic background may also influence their postzygotic mutation profiles.
Assuntos
Epigênese Genética , Sêmen , Adulto , Humanos , Hipóxia , Fator 1 Induzível por Hipóxia , Masculino , MutaçãoRESUMO
Skin infections with cutaneous human papillomavirus (HPV) have been linked to the development of non-melanoma skin cancer, in which mucosal HPV may also play a crucial role. However, systematic investigations of the distribution and associated factors of HPV infection in healthy skin of the general population are scarce. HPV DNA from palmar exfoliated cells of 2,087 individuals was detected by FAP6085/64 and SPF1/GP6+ primers followed by sequencing. A total of 338 papillomavirus types were detected, with HPV-3, HPV-57, and HPV-49 being the most dominant types. The overall prevalence for HPV DNA on skin was 79.92% and for alpha-, beta-, and gamma-HPV were 27.07%, 38.76%, and 29.56%, respectively. Having multiple lifetime sexual partners (adjusted odds ratio 1.60), being a migrant worker (adjusted odds ratio 2.05, reference: farmers), and frequent bathing (Ptrend = 0.001) were associated with alpha-HPV DNA presence. Advancing age increased the detection risk of beta-HPV (Ptrend = 0.001). Higher education (Ptrend = 0.017) and frequent bathing (Ptrend = 0.001) were positively related to gamma-HPV positivity. This study demonstrates that alpha-HPV commonly exists on healthy skin of the general population in rural China, and alpha- and gamma-HPV infections are related to certain behaviors, different from beta-HPV infection. These findings are crucial to better understanding the biology of HPV infection and may be suggestive of the potential transmission of these viruses.
Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Adulto , Distribuição por Idade , Idoso , Biópsia por Agulha , China/epidemiologia , Intervalos de Confiança , DNA Viral/análise , Feminino , Voluntários Saudáveis , Humanos , Imuno-Histoquímica , Modelos Logísticos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Papillomaviridae/genética , Prevalência , Estudos Retrospectivos , Medição de Risco , População Rural , Distribuição por SexoRESUMO
Esophageal squamous cell carcinoma (ESCC) has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional samples using Sanger sequencing. Whole-genome SNP arrays were employed to detect copy number alteration (CNA) and loss of heterozygosity (LOH) in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations (NSSMs) in 102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology (GO) analysis. Tumor genomes with TP53 mutations were significantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B (30.9%), amplification of 11q13.3 covering CCND1 (30.9%), and TP53 point mutation (50.9%) occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC. Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p11.2, and 3p12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes. These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting.
Assuntos
Carcinoma de Células Escamosas/genética , Ciclina D1/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias Esofágicas/genética , Perda de Heterozigosidade , Proteína Supressora de Tumor p53/genética , Adulto , Ciclo Celular , Carcinoma de Células Escamosas do Esôfago , Esôfago/patologia , Exoma/genética , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Dosagem de Genes/genética , Instabilidade Genômica/genética , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genéticaRESUMO
FAP59/64, FAP6085/6319, and CUT primer sets were designed for detecting cutaneous HPV and have been used in many clinical and epidemiology studies. The FAP6085/64 primer set was first evaluated in this study and the FAP6085/64 combination was found to be much more sensitive than all three original primer sets by using HPV plasmids as a template. To confirm further the effectiveness of the FAP6085/64 primer set in human DNA templates, 90 palmar exfoliated cell DNA samples were used to detect the cutaneous HPV by both the FAP59/64 and FAP6085/64 primer sets. The overall proportion of HPV detection in those skin samples was 77.8% (70/90) using FAP6085/64, as compared to 55.6% (50/90) using FAP59/64. The FAP6085/64 primer set was also applied in a population based study. The proportion of HPV detection was 73.96% (2076/2807) in skin samples collected from healthy individuals, and a total of 336 different PV types were found. Sixty (17.9%) of them were fully characterized HPV types, 127 (37.8%) were putative HPV types which had been described previously, 149 (44.3%) were novel putative HPV types, and two animal PVs were also detected. These results suggest that the FAP6085/64 primer set was sensitive and effective for detection of cutaneous HPV in healthy skin samples.