Helicobacter pylori is the primary cause of gastric cancer. However, monoclonal Epstein-Barr virus (EBV) nucleic acid is also present in up to 10% of these tumors worldwide. EBV prevalence is increased with male sex, nonantral localization and surgically disrupted anatomy. To further examine associations between EBV and gastric cancer, we organized an international consortium of 11 studies with tumor EBV status assessed by in situ hybridization. We pooled individual-level data on 2,648 gastric cancer patients, including 184 (7%) with EBV-positive cancers; all studies had information on cigarette use (64% smokers) and nine had data on alcohol (57% drinkers). We compared patients with EBV-positive and EBV-negative tumors to evaluate smoking and alcohol interactions with EBV status. To account for within-population clustering, multilevel logistic regression models were used to estimate interaction odds ratios (OR) adjusted for distributions of sex (72% male), age (mean 59 years), tumor histology (56% Lauren intestinal-type), anatomic subsite (61% noncardia) and year of diagnosis (1983-2012). In unadjusted analyses, the OR of EBV positivity with smoking was 2.2 [95% confidence interval (CI) 1.6-3.2]. The OR was attenuated to 1.5 (95% CI 1.01-2.3) by adjustment for the possible confounders. There was no significant interaction of EBV status with alcohol drinking (crude OR 1.4; adjusted OR 1.0). Our data indicate the smoking association with gastric cancer is stronger for EBV-positive than EBV-negative tumors. Conversely, the null association with alcohol does not vary by EBV status. Distinct epidemiologic characteristics of EBV-positive cancer further implicate the virus as a cofactor in gastric carcinogenesis.

Introducción. La metaplasia intestinal en la unión esofagogástrica puede originarse en el esófago distal por reflujo esofagogástrico o en el estómago proximal, esta lesión premaligna puede progresar a cáncer. Objetivo. Determinar la frecuencia de metaplasia intestinal de la unión esofagogástrica en pacientes con reflujo esofagogástrico clínico y su relación con la gastritis crónica y Helicobacter pylori. Material y Métodos. De marzo de 2001 a junio de 2001 todos los pacientes que fueron referidos al Servicio de Endoscopia sin diagnóstico de cáncer del tracto digestivo y que de acuerdo al cuestionario de Carlsson-Dent se clasificaron con reflujo esofagogástrico fueron incluidos. Se les realizó endoscopia convencional y se tomaron biopsias de la unión esofagogástrica (cardias); todas las muestras fueron revisadas por un patólogo que desconocía el diagnóstico y la metodología del estudio. Resultados. Se incluyeron 51 pacientes; 20 hombres y 31 mujeres, con edad promedio de 53,7 años; el tipo de unión escamo-columnar en 30 pacientes fue heterotópica y tipo"Z" en 21; 17 pacientes tuvieron hernia hiatal, 12 esofagitis aguda, se diagnosticó por endoscopia 6 pacientes con gastritis aguda, 19 con gastritis crónica y 5 casos de esófago de Barrett. Histológicamente se encontraron 3 pacientes con esófago de Barrett; 48 con gastritis crónica, 12 con metaplasia cardial y 34 con Helicobacter pylori. Conclusiones. Doce (23,5%) pacientes presentaron metaplasia intestinal. En el 66,6% de los pacientes se encontró H. pylori; Cuarenta y ocho pacientes tuvieron (94,1%) gastritis crónica y endoscópica-mente el tipo de unión escamo-columnar más frecuente observado fue tipo heterotópica en 58,8% y tipo "Z" en 41,2%. Palabras clave: metaplasia intestinal, reflujo esofagogástrico, Helicobacter pylori, carditis, gastritis. Farfán Hernández A, Hernández Guerrero A, Sobrino Cossío S, Frías Mendívil M, Herrera Goepfert R, Rosales Solís A, Córdova Pluma VH. La asociación entre metaplasia intestinal de la unión esofagogástrica y enfermedad por reflujo gastroesofágico en el Instituto Nacional de Cancerología. Rev Oncol 2003;5(7):390-6

Background: The definition of prognostic factors in gastric carcinoma (GC) remains controversial. The potential of serum albumin as a prognostic factor for GC is emphasized because the technique to measure it is simple as well as being cheap and widely available. Our aim was to define the prognostic role of serum albumin in GC.

Background DNA methylation is an important epigenetic process for transcriptional control of human genome including those genes involved in cancer initiation and progression. Clinical studies have suggested that biological explanation to the protective effect of some nutrients could be linked with the DNA methylation. Folate is a primary methyl donor nutrient; it has been shown to play a key role in DNA methylation, repair and synthesis, by acting as co-factors and/or substrates in this metabolic pathway. Likewise, activity of a key enzyme, the methylenetetrahydrofolate reductase (MTHFR) has also been shown to influence DNA methylation. Overall, these findings support the notion that dietary intake as well as genetic factors play a role in one-carbon metabolism.

To monitor changes along the entire Helicobacter pylori vac A gene we carried out full-length single-step PCR amplification in 21 gastritis and gastric cancer isolates. HindIII restriction analysis led us to detect a > 400-bp internal insertion in vacA subsequently shown to be a direct 451-bp gene duplication. We found HindIII profiles for 16 genes that allowed their grouping into two restriction patterns that were related to theoretical profiles for previously sequenced Western genes. Comparisons with theoretical HindIII patterns for Japanese isolates appear suggestive of geographical H. pylori clonality. Full-length single-step PCR amplification seems suitable for quick restriction pattern assignment and detection of gene size changes.

N-Nitroso compounds (NOC) are potent animal carcinogens and potential human carcinogens. The primary source of exposure for most individuals may be endogenous formation, a process that can be inhibited by dietary polyphenols. To estimate the risk of gastric cancer (GC) in relation to the individual and combined consumption of polyphenols and NOC precursors (nitrate and nitrite), a population-based case-control study was carried out in Mexico City from 2004 to 2005 including 257 histologically confirmed GC cases and 478 controls. Intake of polyphenols, nitrate and nitrite were estimated using a food frequency questionnaire. High intakes of cinnamic acids, secoisolariciresinol and coumestrol were associated with an ~50% reduction in GC risk. A high intake of total nitrite as well as nitrate and nitrite from animal sources doubled the GC risk. Odds ratios around 2-fold were observed among individuals with both low intake of cinnamic acids, secoisolariciresinol or coumestrol and high intake of animal-derived nitrate or nitrite, compared to high intake of the polyphenols and low animal nitrate or nitrite intake, respectively. Results were similar for both the intestinal and diffuse types of GC. Our results show, for the first time, a protective effect for GC because of higher intake of cinnamic acids, secoisolariciresinol and coumestrol, and suggest that these polyphenols reduce GC risk through inhibition of endogenous nitrosation. The main sources of these polyphenols were pears, mangos and beans for cinnamic acids; beans, carrots and squash for secoisolariciresinol and legumes for coumestrol.

Adjuvant chemotherapy is not indicated in lymph node-negative colorectal adenocarcinoma (CRC), even though some cases will present recurrent disease. It is important to identify a subgroup of patients with the highest risk of relapse because of the potential benefit of adjuvant chemotherapy. The objective of this study is to define the prognostic factors and describe a method for the selection of this subgroup. A retrospective cohort of 124 patients with lymph node-negative CRC with complete surgical resection was studied. Cox's proportional hazards model was used to define the prognostic factors associated with CRC-related survival and to develop a method for prediction of recurrence probability. The cohort included 62 women and 62 men with mean age 55.8 years. The mean follow-up period was 11.7 years. T classification of the primary tumor, differentiation grade, carcinoembryonic antigen level, gender and the presence of neural invasion were significant prognostic factors according to the multivariate analysis (final model P=0.00001). Using risk ratios for these prognostic factors, we defined a high-risk group of 78 patients and a low-risk group of 46 patients with 24 and 5 recurrences, respectively (recurrence rates of 30.8% and 10.9% respectively, P=0.011). Using these factors, a prognostic scale was developed to predict high risk of recurrence in cases of completely resected CRC and to identify them as a subgroup of patients with potential benefit of adjuvant chemotherapy.

Objective: To assess gastric cancer survival in relation to dietary intake of methyl donors and the methylenetetrahydrofolate reductase 677C > T (MTHFR 677C > T) polymorphism. Methods: A prospective cohort of 257 incidental, histologically confirmed gastric cancer cases was assembled in January 2004 and followed until June 2006. Patients were recruited from the main oncology and/or gastroenterology units in Mexico City and were queried regarding their sociodemographic information, clinical history, and dietary habits 3 y before the onset of their symptoms. The intake of methyl donors was estimated with a food-frequency questionnaire and the MTHFR 677C > T polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism analysis. Cox's multivariate regression models were used to estimate the mortality risk of gastric cancer. Results: MTHFR 677TT carriers with low folate and vitamin B12 intakes had the lowest survival rate in cases of gastric cancer. High intakes of folate and vitamin B12 before diagnosis was associated with decreased gastric cancer mortality risk in susceptible MTHFR 677TT carriers (mortality risk for folate 0.14, 95% confidence interval 0.04-0.46, P for trend ¼ 0.001; mortality risk for vitamin B12 0.23, 95% confidence interval 0.08-0.66, P for trend ¼ 0.008). Conclusion: Folate and related B vitamins may be used as an intervention strategy to improve the survival outcome of gastric cancer. Ó

It is known that cancer progresses by vertical gene transfer, but this paradigm ignores that DNA circulates in higher organisms and that it is biologically active upon its uptake by recipient cells. Here we confirm previous observations on the ability of cell-free DNA to induce in vitro cell transformation and tumorigenesis by treating NIH3T3 recipient murine cells with serum of colon cancer patients and supernatant of SW480 human cancer cells. Cell transformation and tumorigenesis of recipient cells did not occur if serum and supernatants were depleted of DNA. It is also demonstrated that horizontal cancer progression mediated by circulating DNA occurs via its uptake by recipient cells in an in vivo model where immunocompetent rats subjected to colon carcinogenesis with 1,2-dimethylhydrazine had increased rate of colonic tumors when injected in the dorsum with human SW480 colon carcinoma cells as a source of circulating oncogenic DNA, which could be offset by treating these animals with DNAse I and proteases. Though the contribution of biologically active molecules other than DNA for this phenomenon to occur cannot be ruled out, our results support the fact that cancer cells emit into the circulation biologically active DNA to foster tumor progression. Further exploration of the horizontal tumor progression phenomenon mediated by circulating DNA is clearly needed to determine whether its manipulation could have a role in cancer therapy.

Background. Indications for palliative surgery in gastric carcinoma (GC) are controversial. Our aim was to describe the results of palliative surgery in GC in terms of operative morbidity and survival. Methods. We conducted a retrospective cohort study of patients with GC, who were divided into three groups: resection with microscopic residual disease (R1), palliative resection with macroscopic residual disease (R2), and gastrojejunostomy. Comparisons were tested with analysis of variance (ANOVA) or c 2 test, and the Kaplan-Meier method was used for survival analysis. Results. One hundred and thirty-two patients were included in the study: 21 had R1, 71 had R2, and 40 had gastrojejunostomy. Surgical morbidity was recorded in 4 patients (19%), 23 patients (32.4%), and 1 patient (2.5%) in each of the three groups, respectively (P = 0.001). Operative mortality occurred in 6 patients (8.5%) from the R2 group and in 1 (2.5%) patient from the gastrojejunostomy group (P = 0.406). Median survivals of the R1, R2, and gastrojejunostomy groups were 22.8 months (95% confi dence interval [CI], 16.4-29.3), 12.4 (95% CI, 9.01-15.8) months, and 6.4 months (95% CI, 0-14.6), respectively (P = 0.078) Conclusion. R1 resections and gastrojejunostomy were associated with low surgical morbidity and mortality, unlike R2 resection; in this group, surgical morbidity and mortality was high. Therefore, the benefi t of palliative resection in the presence of extensive residual disease should be balanced against the risk of surgical morbidity.