Gladys Lopez

A case‐control study of gastric cancer in Venezuela

A case‐control study to evaluate risk factors for gastric cancer was carried out among 292 cases of gastric cancer and 485 controls in a high‐risk area of Venezuela. Subjects were interviewed using a structured questionnaire, which elicited information on residential history, socio‐economic status, family history of gastric diseases, smoking, drinking and dietary habits. Habitual diet was estimated from a meal‐structured food frequency questionnaire on 75 food items. There was a strong inverse association with social class, as measured by education and by indicators of poverty. The results of the dietary analysis suggest that a diet high in starch and low in meat, fish and fresh vegetables increases risk of gastric cancer. A protective effect was observed for frequent consumption of allium vegetables. Inverse associations were found with height, which may reflect nutritional status in childhood, and with refrigerator use in the first two decades of life. Alcohol and tobacco consumption was investigated among males only, since the prevalence of alcohol and tobacco use was very low in females. Alcohol drinkers were at higher risk than non‐drinkers and there was a small excess risk for current smokers compared with never smokers. There was some evidence of familial aggregation of gastric cancer. These findings will have important implications in planning preventive strategies for gastric cancer in Venezuela.

Polymorphisms in Genes Related to Bacterial Lipopolysaccharide/Peptidoglycan Signaling and Gastric Precancerous Lesions in a Population at High Risk for Gastric Cancer

As Helicobacter pylori (HP) is a Gram-negative bacterium, we investigated the associations between several functional polymorphisms in genes involved in lipopolysaccharide (LPS) signaling and the prevalence of various stages of gastric premalignant lesions in a Venezuelan population. The two NOD2 polymorphisms, del3020insC and Gly908Arg, were too infrequent to study their associations with gastric lesions. The risk of intestinal metaplasia (IM) was significantly increased among subjects with the CD14 T-260 allele compared to those without this allele. A similar, but nonsignificant increase in risk for dysplasia was observed among homozygotes of this allele. There was no association between TLR4 Asp299Gly polymorphism and any type of lesions, except for a slight nonsignificant increase in risk of IM associated with the AA genotype among subjects with a higher histological HP score. These results suggest that genetic polymorphisms in HP LPS signaling may be implicated in the development of intermediate stages of gastric premalignant lesions.

Host-bacterial interaction in the development of gastric precancerous lesions in a high risk population for gastric cancer in Venezuela.

Helicobacter pylori (HP) infection affects over 50% of the worlds population. The prevalence is over 90% in populations at high risk for gastric cancer, but clinical outcomes of the infection are highly variable and thus host genetic factors have been suggested to play a role in its outcomes in addition to bacterial factors. In this study, we examined the effects of common functional genetic polymorphisms of several proinflammatory cytokines known to be overexpressed in HP‐infected gastric mucosa on the risk of various stages of gastric premalignant lesions. The odds ratios (ORs) and 95% confidence intervals (CI) for atrophic gastritis, intestinal metaplasia and dysplasia were estimated by multinominal logistic regression analysis among 2,033 Venezuelan subjects. There was a significant effect of IL8 ‐251A allele on the prevalence of dysplasia (p = 0.021). The OR associated with the A‐allele was 1.34 (95% CI: 0.82–2.18) for heterozygotes and 2.00 (95% CI: 1.13–3.56) for homozygotes, compared with the TT genotype. Furthermore, there was a statistically significant interaction between the number of A‐alleles and HP cag A genotype (p = 0.009), suggesting that the A‐allele increased the risk of dysplasia only when cag A was present. The OR for the AA compared with TT genotype was 3.22 (95% CI: 1.60–6.52) in this group. There were no associations with other proinflammatory cytokines studied, i.e., IL1β, IL6, monocyte chemoattractant protein 1 (MCP1) and TNFα, or with other stages of premalignant lesions. The present study provides important evidence suggesting host–bacterial interactions in the development of gastric precancerous lesions.

Genetic polymorphisms in mediators of inflammation and gastric precancerous lesions

Chronic inflammation induced by Helicobacter pylori is a key process in gastric carcinogenesis. We hypothesized that genetic polymorphisms in important mediators of H. pylori-induced inflammation may influence the risk of developing various grades of precancerous lesions. We studied the associations between single nucleotide polymorphisms (SNPs) in cyclooxygenase 1 and 2 (PTGS1 and PTGS2), inducible nitric oxide synthase (NOS2A), interferon &ggr; (IFNG) and its receptor (IFNGR1), and risk of gastric precancerous lesions in a Venezuelan population characterized by high rates of H. pylori infection. We found no association of precancerous lesions with SNPs in PTGS1 and in IFNG. A nonsynonymous SNP of NOS2A (Ser608Leu) and an SNP located in the promoter of IFNGR1 (C-56T) were associated with higher risk of atrophic gastritis [odds ratio (OR)=1.37, 95% confidence interval (CI)=1.01–1.86, and OR=1.49, 95% CI=1.01–2.19, respectively]. Two SNPs of PTGS2 were associated with risk of dysplasia (OR=1.60, 95% CI=1.01–2.54, and OR=0.66, 95% CI=0.43–0.99). We conclude that genetic variability in the genes we studied does not play a major role in the early stages of gastric carcinogenesis.

Comparison of polymerase chain reaction and histopathology for the detection of Helicobacter pylori in gastric biopsies.

Using data from a Venezuelan cohort of 1,948 adults, the gastric detection of Helicobacter pylori (H. pylori) by polymerase chain reaction (PCR) of the vacA gene in 1 antral biopsy was compared to the detection of H. pylori by histopathology (hematoxylin–eosin and Giemsa staining) in 5 biopsies (antrum and corpus). Overall, H. pylori was detected in 85% and 95% of the subjects by PCR and histopathology, respectively. When results were analyzed by severity of precancerous lesions, PCR on 1 biopsy detected the bacteria less often than histopathology on 5 biopsies in subjects with normal gastric mucosa and non‐atrophic gastritis. However, in subjects with the most severe lesions (intestinal metaplasia type III and dysplasia), PCR on 1 biopsy detected H. pylori as often as histopathology on 5 biopsies, and significantly more often than histopathology on a single biopsy. In conclusion, these findings confirm that histopathology on 5 biopsies is an accurate tool for H. pylori detection in most subjects, compared to the PCR method on 1 biopsy. Nevertheless, the elevated sensitivity of PCR for detecting the bacteria in advanced precancerous lesions, and the possibility to use PCR to distinguish between cagA‐positive and cagA‐negative strains, makes the PCR technique especially useful in studies of stomach cancer.