PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (1100176)

Clipboard (0)
None

Related Articles

1.  Poor oral hygiene and risk of esophageal squamous cell carcinoma in Kashmir 
British Journal of Cancer  2013;109(5):1367-1372.
Background:
Several studies have suggested an association between poor oral health and esophageal squamous cell carcinoma (ESCC). We conducted a case-control study in Kashmir, a region with relatively high incidence of ESCC in north India, to investigate the association between oral hygiene and ESCC risk.
Methods:
We recruited 703 histologically confirmed ESCC cases, and 1664 controls individually matched to the cases for age, sex, and district of residence. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
Results:
We found an inverse association between teeth cleaning and ESCC risk. As compared with never cleaning teeth, the OR (95% CI) was 0.41 (0.28–0.62) for cleaning less than daily and 0.44 (0.25–0.77) for cleaning at least once a day (P for trend=0.026) in models adjusted for multiple potential confounders, including several indicators of socioeconomic status. This association persisted after we limited our analyses to never tobacco users. The inverse association between cleaning teeth and ESCC was stronger with using brushes than with using sticks/fingers. We also found an association between the number of decayed, filled, and missing teeth and ESCC risk, but the trend of the associations was not statistically significant. Avoiding solid food and cold beverages because of teeth and oral problems were also associated with ESCC risk.
Conclusion:
We found an association between poor oral hygiene indicators and ESCC risk, supporting the previous studies that showed the same associations.
doi:10.1038/bjc.2013.437
PMCID: PMC3778293  PMID: 23900216
esophageal cancer; oral health; dental hygiene; tooth loss; Kashmir
2.  Association of tooth loss and oral hygiene with risk of gastric adenocarcinoma 
Introduction
Poor oral health and tooth loss have been proposed as possible risk factors for some chronic diseases, including gastric cancer. However only a small number of studies have tested these associations.
Method
We conducted a case-control study in Golestan Province, Iran, that enrolled 309 cases diagnosed with gastric adenocarcinoma (118 noncardia, 161 cardia, and 30 mixed-locations) and 613 sex, age and neighborhood matched controls. Data on oral health were obtained through physical examination and questionnaire including tooth loss, the number of decayed, missing, and filled teeth, and frequency of tooth brushing. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models adjusted for potential confounders. Standard one degree-of-freedom linear trend test and a multiple degree of freedom global test of the effect of adding oral hygiene variables to the model were also calculated.
Results
Our results showed apparent associations between tooth loss and DMFT score with risk of gastric cancer, overall and at each anatomic subsite. However, these associations were not monotonic and were strongly confounded by age. The results also showed that subjects who brushed their teeth less than daily were at significantly higher risk for gastric cardia adenocarcinoma OR (95% CI) of 5.6 (1.6–19.3).
Discussion
We found evidence for an association between oral health and gastric cancer, but the non- monotonic association, the relatively strong effect of confounder adjustment, and inconsistent results across studies must temper the strength of any conclusions.
doi:10.1158/1940-6207.CAPR-12-0491
PMCID: PMC3644330  PMID: 23503651
Adenocarcinoma; Tooth loss; Oral health; Stomach
3.  Variations in the MHC Region Confer Risk to Esophageal Squamous Cell Carcinoma on the Subjects from High-Incidence Area in Northern China 
PLoS ONE  2014;9(3):e90438.
Background
The human major histocompatibility complex (MHC) is the most important region in vertebrate genome, and is crucial in innate immunity. Recent studies have demonstrated the possible role of polymorphisms in the MHC region to high risk for esophageal squamous cell carcinoma (ESCC). Our previous genome-wide association study (GWAS) has indicated that the MHC region may confer important risk loci for ESCC, but without further fine mapping. The aim of this study is to further identify the risk loci in the MHC region for ESCC in Chinese population.
Methods
Conditional logistic regression analysis (CLRA) was performed on 24 single nucleotide polymorphisms (SNPs) within the MHC region, which were obtained from the genetically matched 937 cases and 692 controls of Chinese Han population. The identified promising SNPs were further correlated with clinical and clinicopathology characteristics. Immunohistochemistry was performed to explore the protein expression pattern of the related genes in ESCC and neighboring normal tissues.
Results
Of the 24 promising SNPs analyzed, we identified three independent SNPs in the MHC region associated with ESCC: rs35399661 (P = 6.07E-06, OR = 1.71, 95%CI = 1.36–2.17), rs3763338 (P = 1.62E-05, OR = 0.63, 95%CI = 0.50–0.78) and rs2844695 (P = 7.60E-05, OR = 0.74, 95%CI = 0.64–0.86). These three SNPs were located at the genes of HLA-DQA1, TRIM27, and DPCR1, respectively. Further analyses showed that rs2844695 was preferentially associated with younger ESCC cases (P = 0.009). The positive immunostaining rates both for HLA-DQA1 and TRIM27 were much higher in ESCC tissues than in neighboring normal tissues (69.4% vs. 26.8% for HLA-DQA1 and 77.6% vs. 47.8% for TRIM27, P<0.001). Furthermore, the overexpression of HLA-DQA1 is correlated significantly with age (P = 0.001) and family history (P<0.001).
Conclusion
This study for the first time provides evidence that multiple genetic factors within the MHC region confer risk to ESCC on the subjects from high-risk area in northern China.
doi:10.1371/journal.pone.0090438
PMCID: PMC3942432  PMID: 24595008
4.  Predicting esophageal squamous cell carcinoma and squamous dysplasia: risk modeling in a high risk area in Iran 
Archives of Iranian Medicine  2012;15(1):18-21.
Background
Identifying people at higher risk of having squamous dysplasia, the precursor lesion for esophageal squamous cell carcinoma (ESCC), would allow targeted endoscopic screening.
Methods
We used multivariate logistic regression models to predict ESCC and dysplasia as outcomes. The ESCC model was based on data from the Golestan Case-Control Study (total n=871; cases=300), and the dysplasia model was based on data from a cohort of subjects from a GI clinic in Northeast Iran (total n=724; cases=26). In each of these analyses, we fit a model including all risk factors known in this region to be associated with ESCC. Individual risks were calculated using the linear combination of estimated regression coefficients and individual-specific values for covariates. We used cross-validation to determine the area under the curve (AUC) and to find the optimal cut points for each of the models.
Results
The model had an area under the curve of 0.77 (95% CI: 0.74–0.80) to predict ESCC with 74% sensitivity and 70.4% specificity for the optimum cut point. The area under the curve was 0.71 (95% CI: 0.64–0.79) for dysplasia diagnosis, and the classification table optimized at 61.5% sensitivity and 69.5% specificity. In this population, the positive and negative predictive values for diagnosis of dysplasia were 6.8% and 97.8%, respectively.
Conclusion
Our models were able to discriminate between ESCC cases and controls in about 77%, and between individuals with and without squamous dysplasia in about 70% of the cases. Using risk factors to predict individual risk of ESCC or squamous dysplasia still has limited application in clinical practice, but such models may be suitable for selecting high risk individuals in research studies, or increasing the pretest probability for other screening strategies.
PMCID: PMC3294378  PMID: 22208438
5.  Association of p53/p21 expression with cigarette smoking and prognosis in esophageal squamous cell carcinoma patients 
AIM: To investigate the expression of p53 and p21 and associations with possible risk factors, such as cigarette smoking, in esophageal squamous cell carcinoma (ESCC) in northeastern Iran, a region with a high incidence of ESCC.
METHODS: The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffin-embedded blocks of adjacent normal specimens from the cases, along with normal esophageal tissue from 80 healthy subjects.
RESULTS: Positive expression of p53 protein was detected in 56.2% (45/80) of ESCC cases, and in none of the normal esophageal tissue of the control group (P < 0.001). Furthermore, 73.8% (59/80) of ESCC cases and 43.8% (35/80) of controls had positive expression of p21 protein (P < 0.001). Cigarette smoking was significantly associated with p53 over-expression in ESCC cases (P = 0.010, OR = 3.64; 95% CI: 1.32-10.02). p21 over-expression was associated with poorer clinical outcome among the ESCC patients (P = 0.009).
CONCLUSION: Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran. Furthermore, p21 over-expression was found to be associated with poor prognosis, specifically in the operable ESCC patients.
doi:10.3748/wjg.v16.i39.4958
PMCID: PMC2957605  PMID: 20954283
Esophageal squamous cell carcinoma; p53; p21; Immunohistochemistry; Survival; Smoking
6.  The association between dental and periodontal diseases and sickle cell disease. A pilot case-control study 
The Saudi Dental Journal  2014;27(1):40-43.
Objective
This is a pilot case-control study conducted to investigate the prevalence of dental caries and periodontal disease and examine the possible association between oral health deterioration and SCD severity in a sample of Saudi SCD patients residing in the city of Al-Qatif, Eastern Province, Saudi Arabia.
Materials and methods
Dental examination to determine the Decayed, Missing and Filled Teeth index (DMFT), Community Periodontal Index (CPI), and plaque index system were recorded for 33 SCD patients and 33 age and sex-matched controls in the Al-Qatif Central Hospital, Qatif, Saudi Arabia. Self-administered surveys used to assess socio-economic status; oral health behaviors for both SCD patients and controls were recorded. In addition, the disease severity index was established for all patients with SCD. SPSS data analysis software package version 18.0 was used for statistical analysis. Numerical variables were described as mean with a standard deviation.
Results
Decayed teeth were significantly more in individuals with ages ranging from 18 to 38 years with SCD compared to the control group (p = 0.036) due to oral hygiene negligence. The mean number of filled teeth was significantly lower in individuals with SCD when compared to the control group (p = 0.015) due to the lack of appropriate and timely treatment reflected in the survey responses of SCD patients as 15.2% only taking oral care during hospitalization. There were differences between the cases and controls in the known caries risk factors such as income level, flossing, and brushing habit. The DMFT, CPI, and plaque index systems did not differ significantly between the SCD patients and the control group.
Conclusion
Data suggest that patients with SCD have increased susceptibility to dental caries, with a higher prevalence of tooth decay and lower prevalence of filled teeth. Known caries risk factors influenced oral health more markedly than did factors related to SCD.
doi:10.1016/j.sdentj.2014.08.003
PMCID: PMC4273253  PMID: 25544813
Sickle cell disease; Dental caries; Periodontal
7.  PAH exposure in esophageal tissue and risk of esophageal squamous cell carcinoma in northeastern Iran 
Gut  2010;59(9):1178-1183.
Objective
To evaluate the association of polycyclic aromatic hydrocarbon (PAH) exposure in esophageal epithelial tissue and esophageal squamous cell carcinoma (ESCC) case status in an ESCC case-control study in a high-risk population in northeastern Iran.
Design
Immunohistochemical staining of tissue microarrays (TMAs) of non-tumoral esophageal biopsies from ESCC cases and control subjects. Immunohistochemistry was performed using monoclonal antibodies 8E11 and 5D11, raised against benzo[a]pyrene (B[a]P) diol epoxide (BPDE)-I-modified guanosine and BPDE-I-modified DNA, respectively. Staining intensity was quantified by image analysis, and the average staining in three replicates was calculated.
Setting
Rural region in northeastern Iran.
Participants
Cases were patients with biopsy-proven ESCC. Controls were GI clinic patients with no endoscopic or biopsy evidence of ESCC.
Main outcome measure
Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between antibody staining intensity and ESCC case status.
Results
Cultured ESCC cells exposed to B[a]P in vitro showed dose-dependent staining with 8E11, but not with 5D11. With 8E11, sufficient epithelial tissue was available in the TMA cores to analyze 91 cases and 103 controls. Compared to the lowest quintile of 8E11 staining in the controls, adjusted ORs (95% CIs) for the 2nd to 5th quintiles were 2.42, 5.77, 11.3, and 26.6 (5.21–135), respectively (P for trend < 0.001). With 5D11, 89 cases and 101 controls were analyzed. No association between staining and case status was observed (ORs (95% CIs) for the 2nd to 5th quintiles were 1.26, 0.88, 1.06, and 1.63 (0.63–4.21), P for trend = 0.40).
Conclusions
Dramatically higher levels of 8E11 staining were observed in non-tumoral esophageal epithelium from ESCC patients than from control subjects. This finding strengthens the evidence for a causal role for PAHs in esophageal carcinogenesis in northeastern Iran.
doi:10.1136/gut.2010.210609
PMCID: PMC3505022  PMID: 20584779
esophageal squamous cell carcinoma; polycyclic aromatic hydrocarbons; immunohistochemistry; tissue microarray
8.  DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang, China 
AIM: To investigate the role of metabolic enzyme and DNA repair genes in susceptibility of esophageal squamous cell carcinoma (ESCC).
METHODS: A case-control study was designed with 454 samples from 128 ESCC patients and 326 gender, age and ethnicity-matched control subjects. Genotypes of 69 single nucleotide polymorphisms (SNPs) of metabolic enzyme (aldehyde dehydrogenase-2, ALDH2; alcohol dehydrogenase-1 B, ADHB1; Cytochrome P450 2A6, CYP2A6) and DNA repair capacity genes (excision repair cross complementing group 1, ERCC1; O6-methylguanine DNA methyltransferase, MGMT; xeroderma pigmentosum group A, XPA; xeroderma pigmentosum group A, XPD) were determined by the Sequenom MassARRAY system, and results were analyzed using unconditional logistic regression adjusted for age, gender.
RESULTS: There was no association between the variation in the ERCC1, XPA, ADHB1 genes and ESCC risk. Increased risk of ESCC was suggested in ALDH2 for frequency of presence C allele of SNP [Rs886205: 1.626 (1.158-2.284)], XPD for C allele [Rs50872: 1.482 (1.058-2.074)], and MGMT for A allele [Rs11016897: 1.666 (1.245-2.228)]. Five variants of MGMT were associated with a protective effect on ESCC carcinogenesis, including C allele [Rs7069143: 0.698 (0.518-0.939)], C allele [Rs3793909: 0.653 (0.429-0.995)], A allele [Rs12771882: 0.719 (0.524-0.986)], C allele [Rs551491: 0.707 (0.529-0.945)], and A allele [Rs7071825: 0.618 (0.506-0.910)]. At the genotype level, increased risk of ESCC carcinogenesis was found in homozygous carriers of the ALDH2 Rs886205 [CC vs TT, odds ratios (OR): 3.116, 95% CI: 1.179-8.234], MGMT Rs11016879 (AA vs GG, OR: 3.112, 95% CI: 1.565-6.181), Rs12771882 (AA vs GG, OR: 2.442, 95% CI: 1.204-4.595), and heterozygotes carriers of the ALDH2 Rs886205 (CT vs TT, OR: 3.930, 95% CI: 1.470-10.504), MGMT Rs11016879 (AG vs GG, OR: 3.933, 95% CI: 2.216-6.982) and Rs7075748 (CT vs CC, OR: 1.949, 95% CI: 1.134-3.350), respectively. Three variants were associated with a protective effect on ESCC carcinogenesis, carriers of the MGMT Rs11016878 (AG vs AA, OR: 0.388, 95% CI: 0.180-0.836), Rs7069143(CT vs CC, OR: 0.478, 95% CI: 0.303-0.754) and Rs7071825 (GG vs AA, OR: 0.493, 95% CI: 0.266-0.915). Increased risk of ESCC metastasis was indicated in MGMT for frequency of presence C allele [Rs7068306: 2.204 (1.244-3.906)], A allele [Rs10734088: 1.968 (1.111-3.484)] and C allele [Rs4751115: 2.178 (1.251-3.791)]. Two variants in frequency of presence C allele of CYP2A6 [Rs8192720: 0.290 (0.099-0.855)] and A allele of MGMT [Rs2053139: 0.511 (0.289-0.903)] were associated with a protective effect on ESCC progression. Increased risk of ESCC metastasis was found in heterozygote carriers of the MGMT Rs7068306 (CG vs CC, OR: 4.706, 95% CI: 1.872-11.833).
CONCLUSION: Polymorphic variation in ALDH2, XPD and MGMT genes may be of importance for ESCC susceptibility. Polymorphic variation in CYP2A6 and MGMT are associated with ESCC metastasis.
doi:10.3748/wjg.v16.i5.641
PMCID: PMC2816280  PMID: 20128036
Esophageal cancer; Metabolic enzyme gene; DNA repair gene; Carcinogenesis; Metastasis
9.  Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study 
BMC Cancer  2010;10:650.
Background
Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain.
Methods
Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining.
Results
The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 ± 3.19 vs. 361.29 ± 441.75, P = 0.002, respectively). The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022). HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027).
Conclusions
High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC.
doi:10.1186/1471-2407-10-650
PMCID: PMC3001448  PMID: 21108842
10.  Atrophic gastritis: Risk factor for esophageal squamous cell carcinoma in a Latin-American population 
AIM: To study the association between atrophic gastritis (AG) and esophageal squamous cell carcinoma (ESCC) in a Latin-America population.
METHODS: A case-control study was performed at two reference Brazilian hospitals including patients diagnosed with advanced ESCC and dyspeptic patients who had been subjected to upper gastrointestinal endoscopy, with biopsies of the gastric antrum and body. All cases with ESCC were reviewed by a single pathologist, who applied standard criteria for the diagnosis of mucosal atrophy, intestinal metaplasia, and dysplasia, all classified as AG. The data on the patients’ age, sex, smoking status, and alcohol consumption were collected from clinical records, and any missing information was completed by telephone interview. The association between AG and ESCC was assessed by means of univariate and multiple conditional logistic regressions.
RESULTS: Most patients were male, and the median age was 59 years (range: 37-79 years) in both the ESCC and control groups. Univariate analysis showed that an intake of ethanol greater than 32 g/d was an independent risk factor that increased the odds of ESCC 7.57 times (P = 0.014); upon multiple analysis, alcohol intake of ethanol greater than 32 g/d exhibited a risk of 4.54 (P = 0.081), as adjusted for AG and smoking. Smoking was shown to be an independent risk factor that increased the odds of ESCC 14.55 times (P = 0.011) for individuals who smoked 0 to 51 packs/year and 21.40 times (P = 0.006) for those who smoked more than 51 packs/year. Upon multiple analyses, those who smoked up to 51 packs/year exhibited a risk of 7.85 (P = 0.058), and those who smoked more than 51 packs/ year had a risk 11.57 times higher (P = 0.04), as adjusted for AG and alcohol consumption. AG proved to be a risk factor that increased the odds of ESCC 5.33 times (95%CI: 1.55-18.30, P = 0.008) according to the results of univariate conditional logistic regression.
CONCLUSION: There was an association by univariate conditional logistic regression between AG and ECSS in this sample of Latin-American population.
doi:10.3748/wjg.v19.i13.2060
PMCID: PMC3623983  PMID: 23599625
Atrophic gastritis; Esophagus; Squamous cell carcinoma; Risk factor; Alcohol; Tobacco
11.  Association of Common Polymorphisms in TNFA, NFkB1 and NFKBIA with Risk and Prognosis of Esophageal Squamous Cell Carcinoma 
PLoS ONE  2013;8(12):e81999.
Background
Tumour necrosis factor-alpha (TNF-α) and nuclear factor of kappa light chain gene enhancer in activated B cells (NF-κB) play critical role in carcinogenesis processes like tumour initiation, proliferation, migration and invasion. Single nucleotide polymorphisms in TNF-α, NF-κB and its inhibitor IκB genes were shown to be associated with susceptibility and prognosis of several cancers; however, their role in esophageal squamous cell carcinoma (ESCC) is not well recognised. Therefore, in present study, we aimed to investigate association of common polymorphisms in TNFA, NFkB1 and NFKBIA with risk and prognosis of ESCC in northern Indian population.
Methods
We genotyped 290 ESCC patients (including 162 followed up cases) and 311 mean age, gender and ethnicity matched controls for TNFA -308G>A, NFkB1 -94ATTG ins/del and NFKBIA (-826C>T and 3’UTRA>G) polymorphisms using PCR alone or followed by RFLP and TaqMan assay.
Results
TNFA -308GA genotype was associated with increased risk of ESCC specifically in females and in patients with regional lymph node involvement, while, NFKBIA -826CT+TT genotype conferred decreased risk of ESCC in females. Haplotypes of NFKBIA -826C>T and 3’UTRA>G polymorphisms, C-826G3’UTR and T-826A3’UTR, were associated with reduced risk of ESCC. No independent role of NFkB1 -94ATTG ins/del polymorphism in susceptibility of ESCC was found. Multi-dimensionality reduction analysis showed three factor model TNFA-308, NFKBIA-826, NFKBIA 3’UTR as better predictor for risk of ESCC. Furthermore, combined risk genotype analysis of all studied polymorphisms showed increased risk of ESCC in patients with 1-3 risk genotype compared to ‘0’ risk genotype. Survival analysis did not show any significant prognostic effect of studied polymorphisms. However, in stepwise multivariate analysis, metastasis was found to be independent prognostic predictor of ESCC patients.
Conclusion
TNFA-308 and NFKBIA (-826C>T and 3’UTRA>G) polymorphisms may play role in susceptibility but not in prognosis of ESCC patients in northern Indian population.
doi:10.1371/journal.pone.0081999
PMCID: PMC3852749  PMID: 24324738
12.  Dental Status and Associated Factors in a Dentate Adult Population in Bulgaria: A Cross-Sectional Survey 
This study aimed to determine variations in the dental status of a dentate adult population in terms of “decayed,” “missing,” and “filled” teeth in relation to several sociodemographic and behavioral factors. Quota sampling was used to draw 2531 subjects aged 20 years and over. Data were collected by means of a questionnaire and an oral examination. Multiple logistic regression analyses were performed to observe associations between “decayed,” “missing,” and “filled” teeth and the factors of interest. The mean numbers of “decayed,” “missing,” and “filled” teeth were 2.2, 6.7, and 4.9, respectively. Molar teeth were significantly more often “missing” than premolar and anterior teeth. Age, gender, education, and tooth brushing revealed most noticeable associations. Increasing age was associated with a lower chance of having “decayed” and “filled” teeth, but with a higher chance of having “missing” teeth. Females were more likely to have “missing” and “filled” teeth. Higher education was associated with a lower chance of having “missing” teeth. More frequent tooth brushing was associated with a lower chance of having “decayed” and “missing” teeth, but with a higher chance of having “filled” teeth. These risk indicators should be considered in prevention program planning if reduction of tooth loss is to be achieved.
doi:10.1155/2012/578401
PMCID: PMC3359670  PMID: 22654908
13.  Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China 
BMC Cancer  2006;6:287.
Background
Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China.
Methods
A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques.
Results
Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22–6.25; P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05).
Conclusion
Our results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of GSTT1 may play important roles in the development of ESCC in Huaian area, China.
doi:10.1186/1471-2407-6-287
PMCID: PMC1774575  PMID: 17173682
14.  Poor Dental Status and Oral Hygiene Practices in Institutionalized Older People in Northeast Brazil 
In this study we describe the dental status and oral hygiene practices in institutionalized older people and identify factors associated with poor dental status. A cross-sectional study was performed in a nursing home in Fortaleza, the capital of Ceará State (northeast Brazil). The number of decayed, missing, and filled teeth (DMFT) was assessed in the residents of the nursing home (n = 167; mean age = 76.6 years). The mean DMFT value was 29.7; the mean number of missing teeth was 28.4. Ninety-three (58.1%) were edentulous. Almost 90% practiced oral hygiene, but only about half used a toothbrush. Only 8% had visited a dentist in the preceding three months. Most of the variables regarding oral hygiene habits (such as the use of toothbrush, frequency of oral hygiene per day, regular tooth brushing after meals) did not show any significant association with the DMFT. In multivariate regression analysis, age, general literacy level, and practice of oral hygiene were independently associated with the DMFT (R2 = 0.13). Institutionalized older people in northeast Brazil have poor dental status, and oral hygiene practices are insufficient. Dental health education is needed focusing on the special needs of this neglected and socioeconomically deprived population to improve their quality of life.
doi:10.1155/2009/846081
PMCID: PMC2836820  PMID: 20339459
15.  Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma 
Carcinogenesis  2013;34(5):1062-1068.
In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal adenocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag single-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpathways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations.
doi:10.1093/carcin/bgt030
PMCID: PMC3643422  PMID: 23358850
16.  Candidate Gene Association Study of Esophageal Squamous Cell Carcinoma in a High-Risk Region in Iran 
Cancer research  2009;69(20):7994-8000.
A region with a high risk for esophageal squamous cell carcinoma (ESCC) in northeast of Iran was identified more than three decades ago. Previous studies suggest that hereditary factors play a role in the high incidence of cancer in the region. Polymorphisms of several genes have been associated with susceptibility to esophageal cancer in various populations, but these have not been studied in Iran. We selected 22 functional variants (and 130 related tagSNPs) from 15 genes which previously have been suggested to be associated with an increased risk of ESCC. We genotyped a primary set of samples from 451 Turkmen (197 cases and 254 controls). Seven of 152 variants were associated with ESCC at the P = 0.05 level; these SNPs were then studied in a validation set of 1668 cases and controls (Turkmen and non-Turkmen) under dominant and recessive models. In the joint sample set, five variants, from five different genes, showed significant associations with ESCC at the P = 0.05 level. For one variant, in ADH1B, the association was strong and was present in both Turkmen and non-Turkmen. The histidine allele at codon 48 of ADH1B gene was associated with a significantly decreased risk of ESCC under a recessive model (OR = 0.41, 95%, CI = 0.19 to 0.49; P = 4×10−4). For four additional variants, an association was present in the Turkmen subgroup, but the statistical significance of these was less compelling than for ADH1B. Two variants showed deleterious effects and two were protective. The G allele of the c.870A>G variant of CCND1 gene was associated with a 1.5-fold increased risk of ESCC under the recessive model (OR = 1.50, 95% CI = 1.14 to 2.16, P = 0.02) and the A allele of the rs1625895 variant of TP53 gene was associated with a 1.5-fold increased risk of ESCC under a dominant model (OR = 1.54, 95% CI = 1.21 to 4.07, P = 0.005). The C allele of the rs886205 variant of ALDH2 was associated with a decreased risk of ESCC under a recessive model (OR = 0.58, 95% CI = 0.34 to 0.87, P = 0.02) and the A allele of the rs7087131 variant of MGMT was associated with a decreased risk of ESCC under the recessive model (OR = 0.26, 95% CI = 0.05 to 0.49, P=0.01). These results confirm that genetic predisposition to ESCC plays a role in high incidence of this cancer among Turkmens who live in northeast of Iran.
doi:10.1158/0008-5472.CAN-09-1149
PMCID: PMC3505030  PMID: 19826048
Esophageal squamous cell carcinoma; Turkmen population; ADH1B; ALDH2; MGMT; TP53; CCND1
17.  Palmoplantar keratoderma is associated with esophagus squamous cell cancer in Van region of Turkey: a case control study 
BMC Cancer  2005;5:90.
Background
Esophagus squamous cell cancer (ESCC) is the most common cancer in women with 20.2% and second in men with 10.7% relative frequency among all cancer cases diagnosed in Van Region in the east of Turkey. Ninety percent of all esophageal cancer cases are ESCC and 20–30% of them have family history of esophageal cancer. The most clear defined hereditary predisposition associated with ESCC is palmoplantar keratoderma (PPK). To examine the relationship between ESCC and PPK, we have carried out this case control study.
Methods
The case group consisted of 48 subjects who had new diagnosis of ESCC and did not receive any chemo or radiotherapy. The control group consisted of 96 healthy individuals who were visitors of their relatives in the hospital. Two control persons who matched for age, gender, living place (urban /rural) and region were selected for each case. All subjects were evaluated for PPK by dermatologist. Evaluation was graded as none, mild, evident and severe. None and mild subjects were classified as negative for PPK; and others as positive. Relationship between ESCC and PPK was evaluated with odds ratios and confidence intervals for cases with or without family history of ESCC.
Results
The PPK frequencies were 92.3% in ESCC cases with family history, 62.5% in ESCC cases without family history, 70.8% in all ESCC cases, and 28.1% in the control group. Odds ratios for cases with or without family history of esophageal cancer, and for the whole case group were found as 30.7 (95%CI = 3.8–247.4), 4.3 (95%CI = 1.9–9.8) and 6.2 (95%CI = 2.9–13.3) respectively.
Conclusion
Presence of PPK lesions represents genetic susceptibility for ESCC. This susceptibility for ESCC is the highest among those who have PPK lesions and a positive family history of esophageal cancer. Furthermore, a PPK sufferer has an increased risk of developing ESCC even if there is no family history of esophageal cancer.
doi:10.1186/1471-2407-5-90
PMCID: PMC1187881  PMID: 16048655
18.  Do dentists have better oral health compared to general population: a study on oral health status and oral health behavior in Kathmandu, Nepal 
BMC Oral Health  2014;14:23.
Background
Dentists are considered role models by the general population in regards to oral hygiene and oral health behavior. This study aimed to access the oral health status of dentists and laypersons, and compare the dentists’ practice of preventive dentistry and oral self-care behaviors to that of the laypersons.
Methods
This cross-sectional study recruited 472 participants (195 dentists and 277 laypersons from the general population). Their oral health/hygiene behavior was assessed using a standardized close-ended multiple choice questionnaire. Oral examination was performed to assess caries using Decayed Missed Filled teeth (DMFT) index and periodontal status using Community Periodontal Index of Treatment Needs (CPITN).
Results
Ninety-six percent of dentists brushed their teeth at least once daily, using fluoridated toothpaste and 80.5% twice daily. Although 94% of laypersons brushed their teeth once daily, they seldom used fluoridated toothpaste. Ten percent of participants in each group were caries free. The mean number of teeth present in the oral cavity (27.4 versus 25.4), mean number of teeth with caries (1.8 versus 3.7) and fillings (2.5 versus 0.4) were significantly different (p < 0.0001) between dentists and laypersons, respectively. Regarding the periodontal status, 82% of dentists had CPITN score of 0 whereas 71% of laypersons had the highest score 3 (p = 0.007), and 81% of the laypersons reported tooth mobility compared to 1% of dentists (p < 0.0001).
Conclusions
The participating dentists had better periodontal status and better self-reported oral health behaviors than the laypersons. Despite similar prevalence of caries in the two groups, the prevalence of decayed and unfilled teeth was lower among the dentists.
doi:10.1186/1472-6831-14-23
PMCID: PMC3994336  PMID: 24655533
Dentist; Oral health behavior; Oral health status; Dental caries; DMFT; Periodontal status; CPITN
19.  Oral health status of adults in Southern Vietnam - a cross-sectional epidemiological study 
BMC Oral Health  2010;10:2.
Background
Before strategies or protocols for oral health care can be advised at population level, epidemiological information on tooth decay patterns and its effects on oral function are indispensable. The aim of this study was to investigate influences of socio-demographic variables on the prevalence of decayed, missing, filled (DMF) and sound teeth (St) and to determine the relative risk of teeth in different dental regions for D, M, and F, of adults living in urban and rural areas in Southern Vietnam.
Methods
Cross-sectional DMF and St data of 2965 dentate subjects aged 20 to 95 living in urban and rural areas in three provinces were collected by means of a self-administered questionnaire and an oral examination. The sample was stratified by age, gender, residence and province.
Results
The percentage of subjects having missing teeth was high for all ages while it was low for subjects with decayed and filled teeth. The mean number of missing teeth increased gradually by age from approximately 1 in each jaw at the age of 20 to 8 at the age of 80. The number of decayed teeth was relative low at all ages, being highest in molars at young ages. The mean number of filled teeth was extremely low at all ages in all dental regions. Every additional year of age gives a significantly lower chance for decay, a higher chance for missing, and a lower chance for filled teeth. Molars had a significantly higher risk for decay, missing and filled than premolars and anterior teeth. Females had significantly higher risk for decayed and filled teeth, and less chance for missing teeth than males. Urban subjects presented lower risk for decay, but approximately 4 times greater chance for having fillings than rural subjects. Low socio-economic status (SES) significantly increased the chance for missing anterior and molar teeth; subjects with high SES had more often fillings.
Conclusions
The majority of adults of Southern Vietnam presented a reduced dentition. The combination of low numbers of filled teeth and relative high numbers of decayed and missing teeth indicates that the main treatment for decay is extraction. Molars are more at risk for being decayed or missing than premolars and anterior teeth.
doi:10.1186/1472-6831-10-2
PMCID: PMC2841650  PMID: 20226082
20.  Relationship between the expression of hTERT and EYA4 mRNA in peripheral blood mononuclear cells with the progressive stages of carcinogenesis of the esophagus 
Objective
To establish a relationship between esophageal squamous cell diseases and the expression of human telomerase reverse transcriptase (hTERT) and Eyes absent 4 (EYA4) mRNA in peripheral blood mononuclear cells.
Methods
Subjects were 50 patients with esophageal squamous cell carcinoma (ESCC), 50 with dysplasia (ESCD), 50 with basal cell hyperplasia (BCH) and 50 controls. All subjects were residents of Feicheng County, Shandong Province, China , diagnosed by histopathology. Expression of hTERT and EYA4 mRNA in peripheral blood was determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).
Results
The hTERT and EYA4 mRNA positive expression increased according to disease severity. At the cut-off value of ≥ 0.2, the positive expression rates of EYA4 were 14% for controls, 20.0% for BCH, 26% for ESCD and 52% for ESCC, respectively. At the cut-off value of ≥ 0.8, the positive expression rates of hTERT in the four groups were 24%, 30.0%, 52% and 80%, respectively. Using a positive value of 0.47 for EYA4, the testing sensitivities in the ESCD and ESCC groups were 4% and 16%, respectively, and the testing specificity increased to 100%. Using a positive value of 1.0 for hTERT, the testing sensitivities in the ESCD and ESCC groups were 48% and 60%, respectively, and the testing specificity increased to 72%. The testing sensitivities in the predicting ESCD and ESCC in the discriminant model including EYA4 and hTERT and the five traditional risk factors (sex, age, smoking, alcohol drinking, and family history of esophageal cancer) were 70% and 80%, and testing specificities were 76% and 88% respectively. However, the testing sensitivities and specificities in the predicting ESCD and ESCC in the model only including the above five traditional risk factors were lower than that in the former case.
Conclusion
EYA4 and hTERT mRNA expression increased with the severity of esophageal pathological changes and may be useful for identifying high-risk endoscopy candidates or for monitoring changes in premalignant esophageal lesions.
doi:10.1186/1756-9966-28-145
PMCID: PMC2789727  PMID: 19939248
21.  Comparative genomic hybridization analysis of genetic aberrations associated with development of esophageal squamous cell carcinoma in Henan, China 
AIM: To characterize cytogenetic alterations in esophageal squamous cell carcinoma (ESCC) and its metastasis.
METHODS: A total of 37 cases of primary ESCC and 15 pairs of primary ESCC tumors and their matched metastatic lymph nodes cases were enrolled from Linzhou, the high incidence area for ESCC in Henan, northern China. The comparative genomic hybridization (CGH) was applied to determine the chromosomal aberrations on the DNA extracted from the frozen ESCC and metastatic lymph node samples from these patients.
RESULTS: CGH showed chromosomal aberrations in all the cases. In 37 cases of primary ESCC, chromosomal profile of DNA copy number was characterized by frequently detected gains at 8q (29/37, 78%), 3q (24/37, 65%), 5p (19/37, 51%); and frequently detected losses at 3p (21/37, 57%), 8p and 9q (14/37, 38%). In 15 pairs of primary ESCC tumors and their matched metastatic lymph node cases, the majority of the chromosomal aberrations in both primary tumor and metastatic lymph node lesions were consistent with the primary ESCC cases, but new candidate regions of interest were also detected. The most significant finding is the gains of chromosome 6p with a minimum high-level amplification region at 6p12-6q12 in 7 metastatic lymph nodes but only in 2 corresponding primary tumors (P = 0.05) and 20p with a minimum high-level amplification region at 20p12 in 11 metastatic lymph nodes but only in 5 corresponding primary tumors (P < 0.05). Another interesting finding is the loss of chromosome 10p and 10q in 8 and 7 metastatic lymph nodes but only in 2 corresponding primary tumors (P < 0.05).
CONCLUSION: Using the CGH technique to detect chromosomal aberrations in both the primary tumor and its metastatic lymph nodes of ESCC, gains of 8q, 3q and 5p and loss of 3p, 8p, 9q and 13q were specifically implicated in ESCC in Linzhou population. Gains of 6p and 20p and loss of 10pq may contribute to the lymph node metastasis of ESCC. These findings suggest that the gains and losses of chromosomal regions may contain ESCC-related oncogenes and tumor suppressor genes and provide important theoretic information for identifying and cloning novel ESCC-related oncogenes and tumor suppressor genes.
doi:10.3748/wjg.14.1828
PMCID: PMC2700406  PMID: 18350619
Comparative genomic hybridization; Genetic alterations; Esophageal squamous cell carcinoma; Metastatic lymph nodes
22.  Hygiene Self-Care of Older Adults in West Virginia: Effects of Gender 
Purpose
This study investigated whether oral hygiene self-care behavior differs between genders in older adults in Appalachia, a geographic area with significant oral health concerns. Identifying the practices of older adults may provide valuable information for designing interventions, and improving overall oral health outcomes.
Methods
As part of a larger, on-going study on cognition and oral health in later life in Appalachia, a sample of dentate, older adults without dementia aged 70 and above (n =245, 86 men and 159 women) received an oral assessment by either a dentist or dental hygienist. Psychometricians assessed cognition using a standardized battery of neuropsychological tests. They also administered the General Oral Health Assessment Index and conducted structured interviews concerning diet, oral hygiene practices, oral health, social support, income, and years of education.
Results
Over 80% of women (n = 128) and 52.3% of men (n = 45) reported brushing their teeth twice daily. Multivariate logistic regression analysis was conducted, controlling for socioeconomic status, social support (i.e., frequency of contacting friends and relatives), general oral health assessment items, number of decayed, missing, and filled surfaces, plaque index, and having regular dental visits. The results showed that women reported more frequent toothbrushing than their male counterparts (OR=4.04, 95% CI:1.93,8.42).
Conclusion
Older women in West Virginia had significantly better oral hygiene practices than older men, particularly regarding toothbrushing. Interventions are needed to improve older men’s dental hygiene behaviors to improve overall oral health outcomes.
PMCID: PMC3607540  PMID: 22947846
aged; self-care; gender differences; preventive behavior; Appalachia; oral hygiene
23.  Epigenetic inactivation of secreted frizzled-related protein 2 in esophageal squamous cell carcinoma 
AIM: To investigate the expression and methylation status of the secreted frizzled-related protein 2 (SFRP2) in esophageal squamous cell carcinoma (ESCC) and explore its role in ESCC carcinogenesis.
METHODS: Seven ESCC cell lines (KYSE 30, KYSE150, KYSE410, KYSE510, EC109, EC9706 and TE-1) and one immortalized human esophageal epithelial cell line (Het-1A), 20 ESCC tissue samples and 20 paired adjacent non-tumor esophageal epithelial tissues were analyzed in this study. Reverse-transcription polymerase chain reaction (RT-PCR) was employed to investigate the expression of SFRP2 in cell lines, primary ESCC tumor tissue, and paired adjacent normal tissue. Methylation status was evaluated by methylation-specific PCR and bisulfite sequencing. The correlation between expression and promoter methylation of the SFRP2 gene was confirmed with treatment of 5-aza-2’-deoxycytidine. To assess the potential role of SFRP2 in ESCC, we established stable SFRP2-transfected cells and examined them with regard to cell proliferation, colony formation, apoptosis and cell cycle in vivo and in vitro.
RESULTS: SFRP2 mRNA was expressed in the immortalized normal esophageal epithelial cell line but not in seven ESCC cell lines. By methylation-specific PCR, complete methylation was detected in three cell lines with silenced SFRP2 expression, and extensive methylation was observed in the other four ESCC cell lines. 5-aza-2’-deoxycytidine could restore the expression of SFRP2 mRNA in the three ESCC cell lines lacking SFRP2 expression. SFRP2 mRNA expression was obviously lower in primary ESCC tissue than in adjacent normal tissue (0.939 ± 0.398 vs 1.51 ± 0.399, P < 0.01). SFRP2 methylation was higher in tumor tissue than in paired normal tissue (95% vs 65%, P < 0.05). The DNA methylation status of the SFRP2 correlated inversely with the SFRP2 expression. To assess the potential role of SFRP2 in ESCC, we established stable SFRP2 transfectants and control counterparts by introducing pcDNA3.1/v5 hisA -SFRP2 or pcDNA3.1/v5 hisA -empty vector into KYSE30 cells lacking SFRP2 expression. After transfection, the forced-expression of SFRP2 was confirmed by the RT-PCR. In comparison with the control groups, stably-expressed SFRP2 in KYSE 30 cells significantly reduced colony formation in vitro (47.17% ± 15.61% vs 17% ± 3.6%, P = 0.031) and tumor growth in nude mice (917.86 ± 249.35 mm3 vs 337.23 ± 124.43 mm3, P < 0.05). Using flow cytometry analysis, we found a significantly higher number of early apoptotic cells in SFRP2-transfected cells than in the control cells (P = 0.025). The mean cell number in the S and G2-M phases of the cell cycle was also significantly lower in SFRP2-transfected KYSE30 cells compared with mock transfected counterparts.
CONCLUSION: Silencing of SFRP2 expression through promoter hypermethylation may be a factor in ESCC carcinogenesis through loss of its tumor-suppressive activity.
doi:10.3748/wjg.v18.i6.532
PMCID: PMC3280398  PMID: 22363119
Esophageal squamous cell carcinoma; Secreted frizzled-related protein 2; Methylation; Tumor suppressor gene; Wnt signaling pathway
24.  Macronutrients, vitamins and minerals intake and risk of esophageal squamous cell carcinoma: a case-control study in Iran 
Nutrition Journal  2011;10:137.
Background
Although Iran is a high-risk region for esophageal squamous cell carcinoma (ESCC), dietary factors that may contribute to this high incidence have not been thoroughly studied. The aim of this study was to evaluate the effect of macronutrients, vitamins and minerals on the risk of ESCC.
Methods
In this hospital-based case-control study, 47 cases with incident ESCC and 96 controls were interviewed and usual dietary intakes were collected using a validated food frequency questionnaire. Data were modeled through unconditional multiple logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), controlling for age, sex, gastrointestinal reflux, body mass index, smoking history (status, intensity and duration), physical activity, and education.
Results
ESCC cases consumed significantly more hot foods and beverages and fried and barbecued meals, compared to the controls (p < 0.05). After adjusting for potential confounders, the risk of ESCC increased significantly in the highest tertiles of saturated fat [OR:2.88,95%CI:1.15-3.08], cholesterol [OR:1.53, 95%CI: 1.41-4.13], discretionary calorie [OR:1.51, 95%CI: 1.06-3.84], sodium [OR:1.49,95%CI:1.12-2.89] and total fat intakes [OR:1.48, 95%CI:1.09-3.04]. In contrast, being in the highest tertile of carbohydrate, dietary fiber and (n-3) fatty acid intake reduced the ESCC risk by 78%, 71% and 68%, respectively. The most cancer-protective effect was observed for the combination of high folate and vitamin E intakes (OR: 0.02, 95%CI: 0.00-0.87; p < 0.001). Controls consumed 623.5 times higher selenium, 5.48 times as much β-carotene and 1.98 times as much α-tocopherol as the amount ESCC cases consumed.
Conclusion
This study suggests that high intake of nutrients primarily found in plant-based foods is associated with a reduced esophageal cancer risk. Some nutrients such as folate, vitamin E and selenium might play major roles in the etiology of ESCC and their status may eventually be used as an epidemiological marker for esophageal cancer in Iran, and perhaps other high-risk regions.
doi:10.1186/1475-2891-10-137
PMCID: PMC3260093  PMID: 22185224
Esophageal squamous cell carcinoma; macronutrients; vitamins; minerals; Iran
25.  Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma 
PLoS ONE  2014;9(4):e95386.
Aims
The asymptomatic nature of early-stage esophageal squamous cell carcinoma (ESCC) results in late presentation and consequent dismal prognosis This study characterized 14-3-3σ protein expression in the multi-stage development of ESCC and determined its correlation with clinical features and prognosis.
Materials and Methods
Western blot was used to examine 14-3-3σ protein expression in normal esophageal epithelium (NEE), low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), ESCC of TNM I to IV stage and various esophageal epithelial cell lines with different biological behavior. Immunohistochemistry was used to estimate 14-3-3σ protein in 110 biopsy samples of NEE, LGIN or HGIN and in 168 ESCC samples all of whom had follow-up data. Support vector machine (SVM) was used to develop a classifier for prognosis.
Results
14-3-3σ decreased progressively from NEE to LGIN, to HGIN, and to ESCC. Chemoresistant sub-lines of EC9706/PTX and EC9706/CDDP showed high expression of 14-3-3σ protein compared with non-chemoresistant ESCC cell lines and immortalized NEC. Furthermore, the downregulation of 14-3-3σ correlated significantly with histological grade (P = 0.000) and worse prognosis (P = 0.004). Multivariate Cox regression analysis indicated that 14-3-3σ protein (P = 0.016) and T stage (P = 0.000) were independent prognostic factors for ESCC. The SVM ESCC classifier comprising sex, age, T stage, histological grade, lymph node metastasis, clinical stage and 14-3-3σ, distinguished significantly lower- and higher-risk ESCC patients (91.67% vs. 3.62%, P = 0.000).
Conclusions
Downregulation of 14-3-3σ arises early in the development of ESCC and predicts poor survival, suggesting that 14-3-3σ may be a biomarker for early detection of high-risk subjects and diagnosis of ESCC. Our seven-feature SVM classifier for ESCC prognosis may help to inform clinical decisions and tailor individual therapy.
doi:10.1371/journal.pone.0095386
PMCID: PMC3990633  PMID: 24743601

Results 1-25 (1100176)