Re: Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions.
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Antioxidants↗
Biomedical subjects
Pelayo Correa
Publications and source records attributed to Pelayo Correa.
Incidence of esophageal and gastric carcinomas among American Asians/Pacific Islanders, whites, and blacks: subsite and histology differences.
BACKGROUND: The authors examined subsite-specific and histology-specific esophageal and gastric carcinoma incidence patterns among the Asians/Pacific Islander (API) population in the United States and compared them with those among whites and blacks. METHODS: Data on newly diagnosed esophageal and gastric carcinomas during 1996-2000 were obtained from 24 population-based central cancer registries, representing approximately 80% of the API population in the United States. Age-adjusted rates, using the 2000 United States standard population, and age-specific rates were computed by anatomic subsite, histology, race, and gender. The difference in the age-adjusted rates between APIs and other races were examined using the two-tailed z statistic. RESULTS: Greater than 75% of esophageal carcinomas among APIs, both males and females, were squamous cell carcinoma. Adenocarcinoma accounted for <20% of all esophageal carcinomas. This pattern was similar to that among blacks but was completely opposite to that among whites. The rate of esophageal squamous cell carcinoma was 81% higher among API males compared with white males, but it was 64% less compared with black males. The rates of esophageal adenocarcinoma were significantly lower among APIs than among both whites and blacks both males and females. The majority of gastric carcinomas among APIs were noncardia adenocarcinoma, whereas cardia adenocarcinoma accounted for only 11% of gastric carcinomas among API males and 6% of gastric carcinomas among API females. The age-adjusted incidence rate of cardia adenocarcinoma was 23% lower among API males compared with white males, but it was 26% higher compared with black males. In contrast, the rates of noncardia adenocarcinoma among APIs were approximately 3.7 times the rate among whites for both males and females and 33% higher than the rate among blacks. CONCLUSIONS: Subsite-specific and histology-specific incidence patterns of esophagogastric carcinoma among APIs differ from those among whites and blacks. The reasons for significantly higher rates of noncardia adenocarcinoma among APIs compared with whites and blacks need further investigation.
Adenocarcinoma↗
Gastric cancer risk in a Mexican population: role of Helicobacter pylori CagA positive infection and polymorphisms in interleukin-1 and -10 genes.
Several polymorphisms of the IL1B and IL10 gene promoters have been reported to be associated with gastric cancer risk in Caucasians. However, studies in other populations have shown differing results. We aimed to test for associations between polymorphisms in IL1B (-31 and +3954), IL10-592 and IL1RN variable number of tandem repeats (VNTR) and risk of gastric cancer in a Mexican population. DNA was extracted from sera of 183 gastric adenocarcinoma patients and 377 controls. The IL1B-31, IL1B+3954 and IL10-592 biallelic polymorphisms were discriminated using 5' Nuclease (TaqMan) assays and Pyrosequencing. The IL1RN penta-allelic VNTR polymorphism was genotyped using PCR followed by GeneScan analysis. A significant interaction was found between IL1B-31 and CagA status for the risk of intestinal-type gastric cancer (p = 0.023). Among CagA positive subjects, those with IL1B-31CC genotype had an increased risk of intestinal-type gastric cancer (OR 3.19, 95%CI = 1.05-9.68), compared to carriers of IL1B-31TT genotype. In contrast, among CagA negative subjects, no significant association of IL1B-31CC genotype with gastric cancer was observed. The IL10-592CC genotype was associated with more than doubling of the risk of the intestinal-type gastric cancer (OR, 2.20, 95%CI = 1.04-4.65). A nonsignificantly increased risk for intestinal-type gastric cancer was found in IL1RN*2 carriers (OR 1.49, 95%CI = 0.89-2.50). None of these polymorphisms was significantly related to the risk of diffuse-type gastric cancer. No significant association was found between risk of gastric cancer and the IL1B+3954 polymorphism. Individuals carrying 2 or more of the risk-associated alleles (IL1B-31C, IL1RN *2 and IL10-592C) were at increased risk for intestinal-type gastric cancer, compared to those with 0 or 1 risk-associated allele. The risk from multiple risk-associated alleles was especially high in subjects infected with CagA positive H. pylori. Our results support the identification of the IL1B-31 promoter polymorphism as a useful marker for risk of intestinal type gastric cancer in persons with CagA positive H. pylori infections.
Adenocarcinoma↗
Association of interleukin-1beta gene polymorphisms with precancerous gastric lesions in African Americans and Caucasians.
OBJECTIVE: Interleukin-1beta plays an important role in inflammation and gastric physiology. Polymorphisms of the IL1B gene have been associated with gastric atrophy and increased cancer risk, especially in Helicobacter pylori-infected subjects. The aim of this study was to evaluate the relationship between IL1B and IL1 receptor antagonist gene polymorphisms and the risk of multifocal atrophic gastritis in African Americans and Caucasians. METHODS: Genomic DNA was extracted from gastric biopsies of 269 adult outpatients (172 African Americans and 97 Caucasians) undergoing diagnostic upper gastrointestinal endoscopy. Histological diagnosis was evaluated according to the updated Sydney System and H. pylori status was assessed by Steiner silver stain. Polymorphisms of the IL1B gene (-511, -31, and +3954) and the IL1 receptor antagonist were investigated by PCR-RFLP. Logistic regression models were used to identify variables associated with multifocal atrophic gastritis in terms of odds ratios and 95% confidence intervals. RESULTS: Considering subjects with normal histology and nonatrophic gastritis as controls, a significant association was found between IL1B+3954T carrier and multiatrophic gastritis (OR 2.23, 95% CI 1.28, 3.88). Analyses stratified by ethnic group demonstrated similar associations in both African Americans (OR 2.23, 95% CI 1.14, 4.37) and Caucasians (OR 2.04, 95% CI 0.74, 5.65). A positive but not significant association was found between the allele 2 of the IL1RN and the presence of multifocal atrophic gastritis. The remaining proinflammatory polymorphisms were not associated with this precancerous lesion. CONCLUSIONS: Our results suggest that the presence of IL1B+3954T allele is a risk marker for multifocal atrophic gastritis in the population studied.
Adult↗
Genomic changes during chronic Helicobacter pylori infection.
The gastric pathogen Helicobacter pylori shows tremendous genetic variability within human populations, both in gene content and at the sequence level. We investigated how this variability arises by comparing the genome content of 21 closely related pairs of isolates taken from the same patient at different time points. The comparisons were performed by hybridization with whole-genome DNA microarrays. All loci where microarrays indicated a genomic change were sequenced to confirm the events. The number of genomic changes was compared to the number of homologous replacement events without loss or gain of genes that we had previously determined by multilocus sequence analysis and mathematical modeling based on the sequence data. Our analysis showed that the great majority of genetic changes were due to homologous recombination, with 1/650 events leading to a net gain or loss of genes. These results suggest that adaptation of H. pylori to the host individual may principally occur through sequence changes rather than loss or gain of genes.
Adult↗
Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms and gastric cancer: a meta-analysis.
BACKGROUND: Polymorphisms of interleukin-1B (IL1B) and its receptor antagonist (IL1RN) genes have been inconsistently associated with gastric cancer risk. We examined these associations by performing meta-analyses. MATERIALS AND METHODS: Twenty-five studies testing the association between IL1B and/or IL1RN gene polymorphisms and gastric cancer were examined: 14 studies of IL1B-511, 14 studies of IL1B-31, 8 studies of IL1B+3954, and 23 studies of IL1RN. Overall and ethnicity-specific summary odds ratios and corresponding 95% confidence intervals for gastric cancer associated with these polymorphisms were estimated using fixed- and random-effects models. Heterogeneity and publication bias were evaluated. RESULTS: IL1B-511T and IL1RN*2 were associated with gastric cancer risk in Caucasians, but not in Asians. For IL1B-511T, the association in Caucasians was stronger when intestinal-subtype and noncardia gastric cancer cases were examined. A nonsignificant trend was observed between IL1B-31C and gastric cancer in Caucasians. No significant association of IL1B+3954T and gastric cancer risk was detected. Studies with better methodologic characteristics reported stronger effects. There was no evidence of publication bias. CONCLUSION: IL1B-511T is associated with gastric cancer susceptibility in Caucasians. The meta-analyses suggest that the conflicting results among studies may be explained by variation in allele frequencies among the ethnic groups and variation in tumor types, as well as by the methodologic quality of the studies.
Gene Frequency↗
Does Helicobacter pylori cause gastric cancer via oxidative stress?
Epidemiologic evidence strongly supports a causal role for Helicobacter pylori in gastric carcinogenesis. The infection was recognized as a Class I human carcinogen by the International Agency for Research on Cancer in 1994. The bacterium does not induce carcinogenesis by itself. The present scientific consensus is that the bacterial oncogenic role is mediated by the chronic active inflammation it elicits in the gastric mucosa. Although the ultimate basic mechanism of carcinogenesis is unknown, strongly suggestive evidence points to oxidative stress as having a pivotal role in the process. This review discusses some of the evidence accumulated so far to support such a role. Numerous avenues of research are open and represent an intriguing challenge to the scientific community.
Helicobacter Infections↗
Effects of a new Helicobacter pylori infection on height and weight in Colombian children.
PURPOSE: The aim of the study is to investigate whether a new infection caused by Helicobacter pylori in preschool children transiently or permanently affects height and weight. METHODS: A cohort of 347 children from three day care centers was followed up for a median of 494 days. Breath tests and anthropometric measurements were performed every 2 to 4 months. The lag effect of a new infection on linear growth during a period of 8 months was analyzed by using mixed-effects models. RESULTS: One hundred five children (30.3%) became infected during the follow-up period and accumulated 92 person-years of follow-up. A significant decrease in growth velocity was observed during the first 4 months after infection. There was no height catch-up in infected children, and after 8 months, an infected child had a cumulative difference of 0.24 cm (growth velocity; 95% confidence interval, 0.22-0.26) compared with an uninfected child. Newly infected children experienced a small decrease in weight at the first visit compared with uninfected children, which became nonsignificant after the second visit without catch-up. CONCLUSIONS: This study shows a significant and nontransient effect of infection caused by H. pylori on height and weight. Potential interventions that target infected preschool children are likely to prevent growth retardation.
Body Height↗
The role of vegetable and fruit consumption in the aetiology of squamous cell carcinoma of the oesophagus: a case-control study in Uruguay.
There is strong evidence of a protection of high consumption of plant foods against squamous cell carcinoma of the oesophagus, but the respective role of fruits and vegetables is not well elucidated. In the time period 1996-2003, a case-control study designed in order to address this question was conducted in Uruguay. The study included 200 cases and 400 age- and sex-matched controls. High total vegetable and total fruit consumption was the strongest protective food group for this malignancy (OR 0.31, 95% CI 0.18-0.51). When this food group was dissected in total vegetables and total fruits, the latter item was more protective than the former one (OR for total fruits 0.48, 95% CI 0.35-0.66) (p-value for difference between both variables 0.04). Finally, when total fruits were dissected in citrus fruits and other fruits, citrus fruits were strongly associated with a reduction in risk (OR 0.47, 95% CI 0.34-0.67). The results of our study point towards an important role of fruits in the prevention of squamous cell carcinoma of the oesophagus.
Adult↗
New strategies for the prevention of gastric cancer: Helicobacter pylori and genetic susceptibility.
Recently acquired knowledge points to the potential of markedly improved strategies for the prevention of gastric cancer. The International Agency for Cancer Research has reached the conclusion that infection with Helicobacter pylori (H. pylori) is carcinogenic to humans (Group I). The bacterium displays marked genetic heterogeneity. Virulence related genes, especially cag A and vac A s1 m1 are associated with an increased cancer risk. Genetic susceptibility, especially polymorphisms of the cytokine genes may increase cancer risk. Highly susceptible individuals infected with high virulence bacterial genotypes have a markedly increased gastric cancer risk. They should be targeted for endoscopic monitoring to detect advanced precancerous lesions. The state of the art is briefly reviewed and the needed research identified.
Anti-Bacterial Agents↗
Commentary: Is prostate cancer an infectious disease?
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Humans↗
Microsatellite instability in preneoplastic and neoplastic lesions of the gallbladder.
BACKGROUND: Gallbladder cancer is very common in Chile and is the leading cause of cancer deaths in women aged over 40 years. However, there is limited information about the molecular changes involved in its pathogenesis. Microsatellite analysis was performed using polymerase chain reaction (PCR)-based assays to identify genetic loci that were altered in neoplastic and preneoplastic conditions of early and advanced gallbladder cancer. Our findings were then correlated with clinicopathological variables and survival time. METHODS: We selected 59 surgical specimens of gallbladder adenocarcinomas (29 early cancers and 30 advanced cancers) and 22 surgical specimens from patients with chronic cholecystitis from a high-risk area for gallbladder cancer (Temuco, Chile). Laser capture microdissection (LCM) was used to harvest tumor cells and preneoplastic lesions. Microsatellite analysis was performed using 13 different markers. The tumors and preneoplastic lesions were also examined with immunohistochemistry for hMLH1, hMSH2, and hMSH6. RESULTS: We found that 10% (6/59) of gallbladder cancers showed high-frequency microsatellite instability (MSI-H), with identical proportions in both early and advanced cancers. In premalignant lesions adjacent to the six MSI-H tumors, we detected instability in two of six examples of intestinal metaplasia (33%) and five of six examples of dysplasia (83%). All MSI-H cases showed an altered pattern with the antibodies studied. MSI status was not associated with survival or other clinicopathological features. No MSI or immunohistochemical alterations were found in the chronic cholecystitis group. CONCLUSIONS: Microsatellite instability was observed in equal proportions in early and late cancers, and it was also found in premalignant lesions, indicating that inactivation of mismatch repair genes occurs early in gallbladder carcinogenesis.
Adenocarcinoma↗
Squamous and small cell carcinomas of the lung: similarities and differences concerning the role of tobacco smoking.
In the time period 1988-2000, a case-case study on environmental factors and lung cancer risk was conducted in Montevideo, Uruguay. This study was designed in order the establish possible differences between squamous cell carcinomas (SCC) and small cell carcinomas (SCLC) of the lung in relation to tobacco smoking. Three hundred and ninety one (391) patients with small cell carcinoma were compared with 1187 patients with squamous cell carcinoma. Regarding sex, the study included a small number of women (26 with SCLC and 20 with SCC). SCLC was associated with higher risks for smoking status, smoking intensity and cumulative exposure to tobacco smoking when compared with SCC. These three tobacco variables were significantly different between both cell types in men. Smoking duration was significantly higher among SCLC compared with SCC only in women. With decreasing age at starting to smoke, the proportion of SCLC increases at the expense of SCC. Finally, types of tobacco and cigarette were not different between cell types in both sexes. It should be noted that these tobacco variables were not associated with increased risks among SCC, when this cell type was compared with SCLC. These results suggests that SCLC display the strongest relation with tobacco smoking than SCC.
Adult↗
Etiology of gastric cancer: what is new?
Recent advances in understanding of risk factors for gastric cancer have focused attention on genetic polymorphisms in both the human host and in Helicobacter pylori. Variation in genes for cytokines such as interleukin-1beta and its receptor antagonist may allow identification of those individuals predisposed to mount an immune response that puts them at elevated risk for gastric cancer. Likewise, analysis of how genetic variation in the genome of H. pylori may modulate the action of virulence factors like CagA may prove useful in identification of persons for whom H. pylori eradication efforts would be most important. This review examines recent studies on interleukin-1beta polymorphisms and H. pylori CagA variation with respect to their modulation of risk for gastric cancer.
Antigens, Bacterial↗
Intestinal helminthiasis in Colombian children promotes a Th2 response to Helicobacter pylori: possible implications for gastric carcinogenesis.
BACKGROUND: Colombians living in coastal Tumaco have a lower incidence of Helicobacter pylori-associated gastric cancer compared with residents of Pasto in the high Andes. Considering the risk for H. pylori disease seems affected by features of bacterial virulence and host polymorphisms, other poorly understood influences, such as concurrent helminthiasis, may also be important. METHODS: Fecal samples from 211 children were tested for parasites and sera from another cohort of 159 children and 92 adults were tested for IgE and H. pylori-specific IgG. RESULTS: Most individuals (95%) from both areas were H. pylori seropositive, with a predominant response of IgG1 followed by IgG2 and low IgG3 and IgG4 antibodies. Compared with Pasto children, Tumaco children were more commonly infected with helminths (P = 0.000), had higher serum IgE levels (P < 0.03), and had higher Th2-associated IgG1 responses to H. pylori (P < 0.0002). Other IgG isotype responses all increased with age but were not significantly different between children and adults from either area. CONCLUSIONS: These results suggest that intestinal helminthiasis in children promotes Th2-polarizing responses to H. pylori and may decrease gastric cancer risk in these individuals later in life. Concurrent helminthiasis may alter inflammatory responses to H. pylori and thus affect the progression of gastritis to gastric atrophy, dysplasia, and cancer.
Child↗
Duration of exposure, a neglected factor in chemoprevention trials.
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Chemoprevention↗
Dietary patterns and risk of cancer of the oral cavity and pharynx in Uruguay.
From 1995 to 2002, a case-control study on food groups and risk of cancer of the oral cavity and pharynx was conducted in Montevideo, Uruguay. Two hundred thirty cases were frequency-matched to 460 controls on age, residence, and urban/rural status. The study was restricted to men. The relationship between foods and risk of oral and pharyngeal squamous cell carcinoma was examined through: 1) individual food group analysis, 2) factor analysis, and 3) determination of empirical scores. The results were similar. Factor analysis generated 2 patterns, which were labeled as "stew" and "vegetables and fruits." The stew pattern loaded positively on boiled meat, cooked vegetables, potato, and sweet potato. This pattern was directly associated with risk of oral and pharyngeal cancer [odds ratio (OR), 3.75; 95% confidence interval (CI), 1.99-7.06; P value for trend=0.0002]. The vegetables and fruits factor loaded positively on raw vegetables, citrus fruits, other fruits, liver, fish, and desserts. This pattern was inversely associated with risk of oropharyngeal carcinoma (OR, 0.34; 95% CI, 0.18-0.64; P value for trend=0.0008). Joint effects of high intake of risk foods and low intake of protective foods were associated with a risk of 12.0 (95% CI, 4.1-34.6). Our study confirms the important role of dietary factors in oral and pharyngeal cancer risk and suggests that the analysis of dietary patterns is a powerful tool to investigate the links between nutrition and cancer.
Adult↗