Gastric cancer risk in relation to tobacco use and alcohol drinking in Kerala, India-Karunagappally cohort study

AIM: To assess the risk of gastric cancer(GC) in relation to tobacco use and alcohol drinking in the Karunagappally cohort in Kerala, South India.METHODS: This study examined the association of tobacco use and alcohol drinking with GC incidence among 65553 men aged 30-84 in the Karunagappally cohort. During the period from 1990-2009, 116 GC cases in the cohort were identified as incident cancers. These cases were identified from the populationbased cancer registry. Information regarding risk factors such as socioeconomic factors and tobacco and alcohol habits of cohort members were collected from the database of the baseline survey conducted during 1990-1997. The relative risks(RRs) and the corresponding 95% confidence intervals(95%CIs) fortobacco use were obtained from Poisson regression analysis of grouped survival data, considering age, follow-up period, occupation and education.RESULTS: Bidi smoking was associated with GC risk(P = 0.042). The RR comparing current versus never smokers was 1.6(95%CI: 1.0-2.5). GC risk was associated with the number of bidis smoked daily(P = 0.012) and with the duration of bidi smoking(P = 0.036). Those who started bidi smoking at younger ages were at an elevated GC risk; the RRs for those starting bidi smoking under the age of 18 and ages 18-22 were 2.0(95%CI: 1.0-3.9) and 1.8(95%CI: 1.1-2.9), respectively, when their risks were compared with lifetime non-smokers of bidis. Bidi smoking increased the risk of GC among never cigarette smokers more evidently(RR = 2.2; 95%CI: 1.3-4.0). GC risk increased with the cumulative amount of bidi smoking, which was calculated as the number of bidis smoked per day x years of smoking(bidi-year; P = 0.017). Cigarette smoking, tobacco chewing or alcohol drinking was not significantly associated with GC risk. CONCLUSION: Among a male cohort in South India, gastric cancer risk increased with the number and duration of bidi smoking.

Epstein-Barr virus-associated gastric carcinoma: Evidence of age-dependence among a Mexican population

AIM： To investigate features of Epstein-Barr virus （EBV）associated gastric carcinoma （EBVaGC） among a Mexican population. METHODS： Cases of primary gastric adenocarcinoma were retrieved from the files of the Departments of Pathology at the Instituto Nacional de Cancerologia and the Instituto Nacional de la Nutrición in Mexico City. The anatomic site of the gastric neoplasia was identified, and carcinomas were histologically classified as intestinal and diffuse types and subclassified as proposed by the Japanese Research Society for Gastric Cancer. EBV-encoded small non-polyadenylated RNA-1 （EBER-1） in situ hybridization was conducted to determine the presence of EBV in neoplastic cells. RESULTS： We studied 330 consecutive, non-selected, primary gastric carcinomas. Among these, there were 173 male and 157 female patients （male/female ratio 1.1/1）. EBER-1 was detected in 24 （7.3%） cases （male/ female ratio： 1.2/1）. The mean age for the entire group was 58.1 years （range： 20-88 years）, whereas the mean age for patients harboring EBER-1-positive gastric carcinomas was 65.3 years （range： 50-84 years）. Age and histological type showed statistically significant differences, when EBER-1-positive and -negative gastric carcinomas were compared. EBER-1 was detected in hyperplastic- and dysplastic-gastric mucosa surrounding two EBER-1-negative carcinomas, respectively. CONCLUSION： Among Latin-American countries, Mexico has the lowest frequency of EBVaGC. Indeed, the Mexican population 〉50 years of age was selectively affected. Ethnic variations are responsible for the epidemiologic behavior of EBVaGC among the worldwide population.

Risk factors of gastric cancer specific for tumor location and histology in Cali,Colombia

AIM- To examine histology- and tumor-location specific risk factors of gastric cancer （GC）.METHODS： This was subjects were 216 GC the period 2000-2002 non-cancer patients hospital. We obtained habits, and others by a a case-control study. The study patients newly diagnosed during and 431 controls selected from matching in age, gender, and information on lifestyles, dietary questionnaire.RESULTS： The subjects who were not eldest among his/her siblings were at a slightly elevated GC risk （OR 1.3; 95% CI 0.8-2.0）. Salting meals before tasting was related to an increased GC risk （OR 3.5; 95% CI 1.6- 7.3）. Frequent consumptions of fruits （OR 0.3; 95% CI 0.1-1.0） and vegetables （OR 0.3; 95% CI 0.1-1.0） were related to decreased GC risks. On the other hand, frying foods （OR 1.9; 95% CI 1.0-3.6） and cooking with coal （OR 1.8; 95% CI 1.3-2.6） were related to increased GC risks. Neither Lauren＇s histological classification （intestinal and diffuse types） nor tumor location significantly affected those associations except birth order. The subjects who were not eldest among his/her siblings had an increased risk of GCs in the distal and middle thirds, and their ORs were 1.7 （95% CI 1.0-2.8） and 1.9 （95% CI 0.8-4.3）, respectively. The corresponding OR in the upper third stomach was 0.3 （95% CI 0.1-0.9）. The differences of those three ORs were statistically significant （P = 0.010）.CONCLUSION： The present study shows that birth order, salt intake, consumption of fruits and vegetables, the type of cooking, and cigarette smoking are related to GC risk. In histology and tumor-location specific analyses, non-eldest person among their siblings is related to an increased GC risk in the distal and middle thirds of the stomach, and is related to a decreased GC risk in the cardia.

Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile

AIM： To examine the presence of human papillomavirus （HPV） in esophageal squamous cell carcinoma （ESCC） specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively.METHODS： We examined 47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and Chile, respectively. HPV was detected using GP5＋/GP6＋ primer pair for PCR, and confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment was used to identify HPV genotype. In addition, P16^INK4A protein immunostaining of all the specimens was conducted.RESULTS： HPV was detected in 21 ESCC specimens （29%）. Sequencing analysis of L1 region fragment identified HPV-16 genome in 6 Colombian cases （13%） and in 5 Chilean cases （19%）. HPV-18 was detected in i0 cases （21%） in Colombia but not in any Chilean case. Since Chilean ESCC cases had a higher prevalence of HPV-16 （without statistical significance）, but a significantly lower prevalence of HPV-18 than in Colombian cases （P = 0.011） even though the two countries have similar ESCC incidence rates, the frequency of HPV-related ESCC may not be strongly affected by risk factors affecting the incidence of ESCC. HPV-16 genome was more frequently detected in p16 positive carcinomas, although the difference was not statistically significant. HPV-18 detection rate did not show any association with p16 expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but the association was not statistically significant. HPV genotypes other than HPV-16 or 18 were not detected in either country.CONCLUSION： HPV-16 and HPV-18 genotypes can be found in ESCC specimens collected from two South American countries. Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC.

E-cadherin and beta-catenin expression in Epstein-Barr virus-associated gastric carcinoma and their prognostic significance

AIM： To examine the role of E-cadherin and betacatenin in carcinogenesis and to assess their prognostic implication in Epstein-Barr virus-associated gastric carcinomas （EBV-GCs）. METHODS： We compared the frequency of E-cadherin and beta-catenin expression in 59 EBV-GCs and 120 non-EBV-GCs, and examined the association between patients＇ prognosis and the expressions of these proteins. RESULTS： Neither the cellular-membranous nor the cytoplasmic E-cadherin expression showed any difference between EBV-GCs and non-EBV-GCs. On the other hand, loss of membranous expression of beta- catenin occurred more frequently in non-EBV-GCs than EBV-GCs [odds ratio = 0.41; 950 confidence interval （CI）, 0.19-0.90]. Furthermore, the nuclear and/or cytoplosmic expression of beta-catenin was seen more frequently in EBV-GCs than non-EBV-GCs （odds ratio = 2.23; 95% CI, 0.97-5.09）, and was observed in a larger proportion of carcinoma cells of EBV-GCs than non-EBV-GCs （P = 0.024）. Survival analysis for non-EBV-GC revealed that lymph node metastasis was significantly associated with poor prognosis （P 〈 0.001）. Among EBV- GCs, the depth of invasion （P = 0.005）, lymph node metastasis （P = 0.004） and an intestinal type by Lauren classification （hazard ratio = 9.47; 95% CI, 2.67-33.6） were significantly associated with poor prognosis. On the other hand, nuclear and/or cytoplasmic expression of beta-catenin was associated with a better prognosis in patients with EBV-GC （hazard ratio = 0.32; 95% CI, 0.11-0.93）. CONCLUSION： We observed more frequent preservation of beta-catenin in cell membrane and accumulation in nuclei and/or cytoplasm in EBV-GCs than in non-EBV- GCs. Factors involved in the prognosis of EBV-GCs and non-EBV-GCs are different in the two conditions.

Human papilloma virus and esophageal carcinoma in a Latin-American region

AIM:To investigate the presence of high-risk human papilloma virus (HPV) in esophageal squamous cell carcinomas (ESCCs) in a non-selected Mexican population.METHODS: Cases with a pathological diagnosis of squamous cell carcinoma of the esophagus were obtained from Department of Pathology files, at the National Cancer Institute in Mexico City during the period between 2000 and 2008. Slides from each case were reviewed and cases with sufficient neoplastic tissue were selected for molecular analysis. DNA was extracted from paraffin-embedded tissue samples for polymerase chain reaction analysis to detect HPV DNA sequences. Demographic and clinical data of each patient were retrieved from corresponding clinical records.RESULTS: HPV was detected in 15 (25%) of ESCCs. HPV-16 was the most frequently observed genotype, followed by HPV-18; HPV-59 was also detected in one case. Unfortunately, HPV genotype could not be established in three cases due to lack of material for direct sequencing, although universal primers detected the presence of HPV generic sequences. No low-risk HPV genotypes were found nor was HPV-16/18 co-infection. HPV presence in ESCC was not significantly associated with gender, age, alcohol consumption, smoking, anatomic location, or histologic grade. All patients belonged to low and very low socioeconomic strata, and were diagnosed at advanced disease stage. Male patients were most commonly affected and the male:female ratio in HPV-positive ESCC increased two- fold in comparison with HPV-negative cases (6.5:1 vs 3.1:1).CONCLUSION: High prevalence of high-risk HPV in ESCC in Mexico does not support the hypothesis that HPV-associated ESCC is more common in areas with higher ESCC incidence rates.

Human papillomavirus in upper digestive tract tumors from three countries

AIM: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses. METHODS: The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16INK4a expression in HPV-positive and HPV-negative cases was also made. RESULTS: HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16INK4a proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and-negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs. CONCLUSION: Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.