Nutrient patterns and risk of esophageal squamous cell carcinoma: a case-control study

Although Iran is a high-risk country for esophageal squamous cell carcinoma (ESCC), the contribution of overall nutrient intakes to this high incidence rate is not yet clear. The aim of this study was to examine the association between nutrient patterns and risk of ESCC in Iran. Forty-seven patients with ESCC and 96 frequency-matched hospital controls underwent private interviews, and dietary habits were collected using a validated food-frequency questionnaire. Factor analysis was conducted and two major nutrient patterns were retained; factor 1 (high in pantothenic acid, vitamin C, potassium, vitamin B(6), magnesium, folate, thiamin, copper, carbohydrate, vitamin K, niacin, α-tocopherol, zinc, total fiber, fluoride, and polyunsaturated fatty acids) and factor 2 (high in saturated fatty acid, biotin, selenium, monounsaturated fatty acids, riboflavin, sodium, fat, cholesterol, calcium, phosphorus, protein, iron, vitamin E, manganese, vitamin D, and vitamin B(12)). Factor 2 was inversely associated with ESCC (OR = 0.06, 95% CI: 0.01-0.28; P = 0.008), whereas no significant association was found for factor 1 (OR = 0.45, 95% CI: 0.11-1.82). The results of the present study suggested a possible role for a nutrient pattern similar to factor 2 in reducing the risk of ESCC.     

Human papillomavirus detected in esophageal squamous cell carcinoma in Iran

IntroductionConsidering the different results obtained regarding the association of HPV with the development of esophageal squamous cell carcinoma (ESCC) in different populations, we aimed to determine the frequency of HPV infection and its subtypes in ESCC in Iranian patients.MethodA total of 100 paraffin-embedded tissue samples of ESCC diagnosed during 1991 and 2005 in the Institute of Cancer affiliated to Tehran University of Medical Sciences were selected. Seven out of 100 samples were excluded due to low quality of extracted DNA from paraffin-embedded specimens. Thus, 93 samples were included for HPV genotyping.ResultAll samples were examined using SPF10 primers for HPV detection. HPV DNA was positive in 8 out of 93 (8.6%) ESCC specimens. Using INNO-LiPA genotyping system we detected the genotypes of 5 out of 8 HPV-positive samples. Both HPV types 16 and 6 were detected in 3 specimens; one sample was positive for HPV type 18 and 2 samples were co-infected with two HPV types. There were no statistically significant differences between HPV-positive and HPV-negative cases with regard to clinical and pathologic findings. Three samples were positive for SPF10 indicating HPV infection; however, the exact HPV type could not be clarified using INNO-LiPA genotyping .ConclusionIn conclusion, the present study showed that a small proportion of ESCC specimens from Iran harbor HPV16, 18 genome using a highly sensitive method. As different rates have been reported from Iran, a more widespread study with more precise definition of geographical differences could delineate the potential involvement of HPV in the development of ESCC in Iranian population.     

Adherence to dietary recommendations and risk of metabolic syndrome: Tehran Lipid and Glucose Study

The “Dietary Guidelines for Americans Adherence Index (DGAI) 2005” was developed based on the latest dietary recommendations to assess the contribution of dietary patterns to chronic diseases. The objective of the study was to evaluate the association of dietary patterns as measured by the modified DGAI 2005 with both the prevalence of metabolic syndrome (MetS) and the MetS risk factors. In this population-based cross-sectional study, 2504 adults (1120 men and 1384 women), aged 19 to 70 years, were randomly selected from the third phase of the Tehran Lipid and Glucose Study. Usual dietary intake was assessed using a food frequency questionnaire, and the DGAI score was calculated for all participants. Metabolic syndrome was defined according to Adult Treatment Panel III diagnostic criteria. Generally, mean values for waist circumference, triglyceride, and blood pressure were significantly higher among male compared with female participants (P < .05). Low high-density lipoprotein cholesterol was the most prevalent MetS risk factor among both men (65.4%) and women (72.5%). After mutual adjustment for confounding variables, those in the highest quartile category of DGAI had a 21% lower prevalence of MetS risk factors clustering than those in the lowest quartile (odds ratio [OR], 0.79; confidence interval [CI], 0.63-0.92; P for trend = .02). Being in the highest quartile category of DGAI score was shown to significantly reduce the prevalence of hyperglycemia (OR, 0.64; CI, 0.47-0.86; P for trend < .001), hypertension (OR, 0.76; CI, 0.70-0.93; P for trend = .05), and low high-density lipoprotein cholesterol (OR, 0.69; CI, 0.54-0.94; P for trend < .001). Consuming a diet consistent with new dietary guidelines was associated with lower risk of MetS prevalence and some of its risk factors. Preventive interventions for MetS risk reduction should focus on the overall dietary pattern.     

Role of podoplanin expression in esophageal squamous cell carcinoma: a retrospective study

Lymphatic metastasis is the predominant cause of the low overall survival of patients with esophageal squamous cell carcinoma (ESCC), as there are no faithful methods available predicting early metastasis. Recent studies suggest an effect of podoplanin expression on metastatic spreading to lymph nodes. The purpose of this study was to investigate the influence of podoplanin expression on lymphatic metastasis and tumor cells, and to find the relationship between podoplanin expression and prognosis of patients with ESCC. We evaluated the level of podoplanin expression on tumor cells and the lymphatic vessel density change of tumor mass compared with normal tissue from the same patient through D2-40 immunohistochemistry staining, and analyzed associations between these two variables and various clinicopathologic parameters individually or conjunctively. There was an association between podoplanin expression and the frequency of lymph node metastases. In 45 patients (80%), podoplanin was expressed on the tumor cells. Twenty-one patients (37.5%) showed high levels of expression. The 5-year disease-free survival rate (5%) for patients with high levels of podoplanin expression was significantly lower (P < 0.001) than for patients with low and moderate expression of podoplanin (54% and 27%, respectively). We concluded that podoplanin is expressed frequently in ESCC, and that the expression of podoplanin on cancer cells, lymphatics, or both is correlated with lymphatic metastasis and clinical outcome.     

食管基底细胞样鳞状细胞癌免疫组化研究

目的了解食管基底细胞样鳞状细胞癌(BSC)的生物学特点.方法 BSC8例,用CK4,CK18,CK19,EMA,CEA,SMA,S100,LN,ColⅣ,NSE,PCNA,p53等12种抗体,进行免疫组化检测,用常规ABC法.结果 BSC的两种细胞成分,基底样细胞(BC)和鳞状细胞(SC)对上述抗体反应截然不同.BC绝大部分病例(7例)专一地对CK19抗体呈阳性反应,而对其他4种上皮性抗体呈阴性;BC有4例对α-SMA及S-100肌性抗体呈阳性;BC巢内玻璃样物对LN及ColⅣ呈阳性反应;BC有较高的PCNA指数,平均54%.相反,SC全部病例均对CK4,CEA,EMA等上皮性抗体呈阳性,而对CK19,SMA,S-100阴性.PCNA指数也较低,平均25%.结论食管BSC为多向分化的高度恶性肿瘤,BC代表向基底细胞和肌上皮方向分化,其增殖活性强,而SC代表向典型的鳞状细胞分化.     

A study on p53 gene alterations in esophageal squamous cell carcinoma and their correlation to common dietary risk factors among population of the Kashmir valley

AIM: To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma (ESCC) among the Kashmiri population of Northern India. METHODS: All cases (n=51) and controls (n = 150) were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases (n = 45) and inpatient controls (n = 150) with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient's age group. Correlation of genetic lesion in p53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls. RESULTS: Thirty-five of 45 (77.8%) histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed germline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 (77.7%), that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance (P<0.05) with familial history of cancer (CD=58), suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable "Hakh" (CD=19.5), red chillies (CD=20.2), hot salty soda tea (CD = 2.37) and local baked bread (CD=1.1). CONCLUSION: Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea, meat, baked bread and "Hakh", that are rich in nitrosoamines and familial cancer history.     

Clinicopathologic study of esophageal squamous cell carcinoma confined to the mucosa.

The authors studied patients with esophageal squamous cell carcinoma confined to the mucosa (ESCM) with respect to various clinicopathologic factors to investigate the course of invasion of very early-stage esophageal cancers. A total of 74 patients with ESCM were studied. Fifty of these patients had tumor invasion of the basement membrane confined to the lamina propria mucosae (m2 cancer), and 24 patients had tumor invasion of the muscularis mucosa (m3 cancer). All lesions were investigated with regard to clinicopathologic factors such as tumor differentiation, pattern of invasion, endoscopic morphology, and inflammatory response. The patients were divided into groups of 8 patients with positive lymphatic invasion, lymph node involvement, or both (Inv[+] group), and a group of 66 patients with no lymphatic invasion or lymph node involvement (Inv[-] group). The inflammatory response was evaluated on the basis of lymphocyte infiltration at the tumor invasion front and lymphocytic follicles beneath the tumor invasion front. Mean lesion size was significantly greater in the Inv(+) group than in the Inv(-) group (p < 0.05). However, there was no significant difference in the mean area of invasion of the lamina propria mucosae or deeper between the Inv(+) group and Inv(-) group. Patients with m2 cancer had a significantly higher rate of high-degree lymphocytic follicles than those with m3 cancer (p < 0.01). In patients with m2 cancer, the mean area of invasion of the lamina propria mucosae in patients with high-degree lymphocytic follicles was significantly greater than that in patients with low-degree lymphocytic follicles (p < 0.05), whereas there was no significant difference in mean lesion size between patients with high-degree and low-degree lymphocytic follicles. In patients with ESCM, lesion size was an important risk factor for lymphatic invasion and nodal involvement, lymphocytic follicles were prominent beneath the front of relatively broad cancer invasion, and lymphocytic follicles were less common with deeper cancer invasion.     

Expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 in esophageal squamous cell carcinoma

正Objective To analyze the expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 (ESCCAL-1) in esophageal squamous cell carcinoma (ESCC) tissues.Methods From August 2011 to May 2013, 73 patients with ESCC,who received radical resection in the First Affiliated Hospital of Zhengzhou University and Henan Cancer Hospi-     

P53 gene codon 72 polymorphism and risk of esophageal squamous cell carcinoma: a case/control study in a Chinese population

SUMMARY.  The aims of this study were to investigate whether p53 gene codon 72 polymorphism was a biomarker associated with esophageal squamous cell carcinoma (ESCC) and its relationship with smoking status in China. The p53 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism among 673 patients with ESCC and 694 healthy controls. The association between p53 genotypes and risk of developing ESCC was estimated by odds ratios (OR) and their 95% confidence intervals (CIs) computed by logistic regression. Compared with Arg/Arg homozygotes, Pro/Pro homozygotes had a nearly twofold increased risk (adjusted OR, 1.83; 95% CI, 1.35–2.48). For the Pro/Arg heterozygotes, there was no evident increased risk (adjusted OR, 1.01, 95% CI, 0.78–1.30). Furthermore, the risk associated with the Pro/Pro variant genotype was more pronounced in younger patients at diagnosis (= 45 years) (OR, 7.4; 95% CI, 1.44–37.89, P  = 0.02), in women (OR, 3.15; 95% CI, 1.52–4.53, P  = 0.02) and in non-smokers (OR, 2.49; 95% CI, 1.58–3.94) and light smokers (OR, 2.13; 95% CI, 1.15–3.93). But tests for homogeneity between smoking-related OR showed no significant differences ( P  = 0.4). The p53 gene codon 72 Pro/Pro genotype was significantly associated with the increased risk of ESCC in a Chinese mainland population and may be an independent factor in susceptibility to ESCC. The association was especially noteworthy in women and in younger patients.     

High prevalence of human papillomavirus in esophageal squamous cell carcinoma: a study in paired samples

Esophageal squamous cell carcinoma (ESCC) is one of the common cancers with a poor prognosis. Incidences of human papillomavirus (HPV) infection range from 0 to 67% in different parts of the world. It has been frequently associated with high‐risk HPV genotypes 16 and 18. The present study analyzes the prevalence of HPV infection in ESCC tumor and adjoining mucosa. Fresh tissue samples were obtained from ESCC tumor (group I) and adjoining mucosa (group II). Aliquots of DNA extracts were used. There were 23 patients with paired samples, 19 (83%) were male. HPV was positive in 20/23 (87%). Mean age of HPV positive in group I was 56.63 ± 6.96 and in group II 54.31 ± 7.13 years (P > 0.05). Majority had more than one viral type. HPV52 was the most common observed in 14 (61%) males and two (9%) females. Other common viruses were HPV55, 39, and 59. Smoking had a significant association with viral positivity. p63 and p16 oncoproteins correlated with degree of tumor differentiation but not with viral status. We documented high prevalence of high‐risk HPV in ESCC. Our observations support the concept of persistent infection by an oncogenic HPV in cancer development. Our study highlights importance of documenting viral genotype in a defined geographic area.     

Radiation-induced esophageal squamous cell carcinoma in situ

A report of radiation-induced squamous cell carcinoma in situ of the esophagus is presented. This report indicates that the patient developed the carcinoma in situ many years after chest wall irradiation for breast cancer treatment. A review of the literature with respect to carcinogenesis after radiotherapy is included and recommendations for the follow-up of patients having mediastinal radiation are suggested.     

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

AIM： TO determine whether -1195 A→G and/or -765 G→C polymorphisms in Cyclooxygenase-2 CCOX-2） may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS： Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios （OR） and 95% confidence intervals （CI） were estimated. RESULTS： The distribution of the -1195A→G polymorphism was significantly different in esophageal cancer patients compared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma （OR = 3.85, 95% CI： 1.45-10.3） compared with the -1195AA genotype as a reference. The -765 G→C genotype distribution was not different between the two groups. The GG/ GG haplotype was present more often in esophageal adenocarcinoma patients than in controls （OR = 3.45, 95% CI： 1.24-9.58; with AG/AG as a reference）. The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance. CONCLUSION： Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.     

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,E...     

Maté consumption and the risk of esophageal squamous cell carcinoma: a meta‐analysis

Maté, a tea‐like infusion of Ilex paraguariensis, is suspected to be a risk factor for esophageal squamous cell carcinoma; however, no meta‐analysis on the subject has been performed to date. A meta‐analysis of studies reporting the consumption of maté in patients with esophageal squamous cell carcinoma was conducted to provide a quantitative estimate of the risk of esophageal squamous cell carcinoma associated with maté consumption. A search was conducted through MEDLINE, PubMed, EMBASE, and Current Contents Connect to April 5, 2012. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using a random effects model for the risk of esophageal squamous cell carcinoma associated with exposure to maté (ever‐ vs. never‐drinkers), as well as for the dose‐dependent risk of esophageal squamous cell carcinoma associated with different levels of maté consumption (highest vs. lowest intake). Nine studies, with 1565 esophageal squamous cell carcinoma cases, met our inclusion criteria. Esophageal squamous cell carcinoma was associated with exposure to maté drink, with an OR of 2.57 and a 95% CI of 1.66–3.98. There was an increased risk of esophageal squamous cell carcinoma associated with a higher consumption of maté versus low consumption (OR 2.76, 95% CI 1.33–5.73 vs. OR 1.84, 95% CI 1.12–3.00). Heterogeneity was observed in the ever versus never and the high‐consumption analyses but not in the low‐consumption analysis. Publication bias was present. Maté consumption was associated with an increased risk of esophageal squamous cell carcinoma.     

Primary radiotherapy with or without chemotherapy in non-metastatic esophageal squamous cell carcinoma: a retrospective study

The purpose of this study was to report the outcome of radio(chemo)therapy in the curative management of esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed 163 patients with T1‐T4, N0‐1, M0 ESCC who were treated between January 1988 and December 2006 at the Technische Universität München. One hundred sixty patients were inoperable due to a poor performance status, comorbidities or locally advanced unresectable disease. External beam radiation therapy (EBRT) was performed with (n= 146) or without (n= 17) systemic chemotherapy. Fifty‐four patients received an additional boost with intraluminal brachytherapy (IBT). Surviving patients were followed for a median of 72 months (range 10–173 months). The estimated overall survival (OS) at 2 and 5 years was 27 ± 4% and 11 ± 3%, respectively. Loco‐regional recurrence at the primary site was observed in 29% of patients (n= 47). The recurrence‐free survival (RFS) at 2 and 5 years was 24 ± 3% and 9 ± 2%, respectively. In multivariate analyses, the ECOG performance status (P= 0.004), 3D conformal (vs conventional) radiotherapy (P= 0.031) and continuous standard fractionation (vs split‐course radiotherapy, P= 0.048) were associated with a better OS. Simultaneous chemotherapy (P= 0.49) or IBT (P= 0.31) had no significant impact on survival. Outcome for patients with ESCC is poor. Despite the very unfavorable patient selection (poor performance status, high rate of comorbidities, and advanced disease), long‐term survival with radio(chemo)therapy was achieved in about 10% of patients. The introduction of modern treatment techniques/modalities (3D conformal planning/ continuous standard fractionation) might be associated with better outcomes.