Association between salt intake and gastric atrophy by Helicobacter pylori infection: first results from the Epidemiological Investigation of Gastric Malignancy (ENIGMA).

PURPOSE: Gastric atrophy (GA), usually linked to chronic infection with Helicobacter pylori (H. pylori), may over time evolve into gastric malignancy. Besides H. pylori, high salt intake may play a role in GA development. This study evaluates cross sectionally the association between salt intake and GA in Chilean adults. METHODS: Population-based samples were recruited from two sites, Antofagasta and Valdivia, partaking in the Epidemiological Investigation of Gastric Malignancies. At recruitment, participants answered questionnaires and provided biospecimens. Salt intake (g/day) was estimated from casual spot urine samples using the Tanaka equation. GA was determined by serum pepsinogen levels. Only participants ≥ 40 to 70 years of age were considered in this analysis, n = 565. For the association between salt intake (as sex-specific quartiles) and GA, odds ratios (ORs) and the corresponding 95% confidence intervals (CI) were estimated through multivariable logistic regression. RESULTS: In women, the multivariable-adjusted OR for GA comparing quartile 4 of the estimated salt intake (12.8 g/day) to quartile 1 (6.6 g/day) was 1.18 (95% CI 0.52-2.68, P-trend = 0.87). The corresponding OR in men was 0.49 (95% CI 0.19-1.27, P-trend = 0.17) with salt intakes of 12.8 g/day and 7.1 g/day for quartiles 4 and 1, respectively. CONCLUSION: There was little evidence for an association between salt intake estimated from spot urine and GA risk in our cross-sectional analysis of middle aged and older adults in Chile. Reverse causation bias cannot be ruled out and the sample size was limited to provide more precise estimates.

Gallbladder cancer: incidence and survival in a high-risk area of Chile.

We assessed population incidence rates 1998-2002 and 5-year survival rates of 317 primary gallbladder cancer (GBC) entered in the population-based cancer registry in Valdivia. We analyzed GBC incidence (Poisson regression) and GBC survival (Cox regression). Cases were identified by histology (69.4%), clinical work-up (21.8%), or death certificate only (8.8%). Main symptoms were abdominal pain (82.8%), jaundice (53.6%) nausea (42.6%), and weight loss (38.2%); at diagnosis, 64% had Stage TNM IV. In the period, 4% of histopathological studies from presumptively benign cholecystectomies presented GBC. GBC cases were mainly females (76.0%), urban residents (70.3%), Hispanic (83.7%) of low schooling <4 years (64.0%). GBC standardized incidence rate per 100,000 (SIR) were all 17.5 (95%CI: 15.5-19.4), women 24.3, and men 8.6 (p < 0.00001); Mapuche 25.0, Hispanic 16.2 (p = 0.09). The highest SIRs were in Mapuche (269.2) and Hispanic women (199.6) with <4 years of schooling. Lowest SIRs were among Hispanic men (19.8) and women (21.9) with >8 years of schooling. Low schooling, female and urban residence were independent risk factors. By December 31, 2007, 6 (1.9%) cases were living, 280 (88.3%) died from GBC, 32 (10.1%) were lost of follow-up. Kaplan Meier Global 5-year survival was: 10.3%, 85% at stage I and 1.9% at stage IV; median survival: 3.4 months. Independent poor prognostic factors were TNM IV, jaundice and nonincidental diagnoses. Our results suggest that women of Mapuche ancestry with low schooling (>50 years) are at the highest risk of presenting and dying from GBC and should be the target for early detection programs.

Regional variations in Helicobacter pylori infection, gastric atrophy and gastric cancer risk: The ENIGMA study in Chile.

BACKGROUND: Regional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk. METHODS: We selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1-69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens). RESULTS: H. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children <10 years old, 40% among 10-19 year olds, 60% in the 20-29 year olds and close to or above 80% in those 30+ years. The comparison of the prevalence of known and potential H. pylori cofactors in gastric carcinogenesis between the high and the low risk area showed that consumption of chili products was significantly higher in Valdivia and daily non-green vegetable consumption was more common in Antofagasta. Pepsinogen levels suggestive of gastric atrophy were significantly more common and occurred at earlier ages in Valdivia, the higher risk area. In a multivariate model combining both study sites, age, chili consumption and CagA were the main risk factors for gastric atrophy. CONCLUSIONS: The prevalence of H. pylori infection and its virulence factors was similar in the high and the low risk area, but atrophy was more common and occurred at younger ages in the higher risk area. Dietary factors could partly explain higher rates of atrophy and gastric cancer in Valdivia. IMPACT: The ENIGMA study in Chile contributes to better understanding regional variations in gastric cancer incidence and provides essential information for public health interventions.

Incidence and survival of stomach cancer in a high-risk population of Chile.

AIM: To study the incidence and survival rate of stomach cancer (SC) and its associated factors in a high risk population in Chile. METHODS: The population-based cancer registry of Valdivia, included in the International Agency for Research on Cancer system, covers 356 396 residents of Valdivia Province, Southern Chile. We studied all SC cases entered in this Registry during 1998-2002 (529 cases). Population data came from the Chilean census (2002). Standardized incidence rates per 100 000 inhabitants (SIR) using the world population, cumulative risk of developing cancer before age 75, and rate ratios by sex, age, ethnicity and social factors were estimated. Relative survival (Ederer II method) and age-standardized estimates (Brenner method) were calculated. Specific survival rates (Kaplan-Meier) were measured at 3 and 5 years and survival curves were analyzed with the Logrank and Breslow tests. Survival was studied in relation to demographics, clinical presentation, laboratory results and medical management of the cases. Those variables significantly associated with survival were later included in a Cox multivariate model. RESULTS: Between 1998 and 2002, 529 primary gastric cancers occurred in Valdivia (crude incidence rate 29.2 per 100 000 inhabitants). Most cases were male (69.0%), residents of urban areas (57.5%) and Hispanic (83.2%), with a low education level (84.5% < 8 school years). SC SIR was higher in men than women (40.8 and 14.8 respectively, P < 0.001), risk factors were low education RR 4.4 (95% CI: 2.9-6.8) and 1.6, (95% CI: 1.1-2.1) for women and men respectively and Mapuche ethnicity only significant for women (RR 2.2, 95% CI: 1.2-3.7). Of all cases, 76.4% were histologically confirmed, 11.5% had a death certificate only (DCO), 56.1% were TNM stage IV; 445 cases (84.1%) were eligible for survival analysis, all completed five years follow-up; 42 remained alive, 392 died of SC and 11 died from other causes. Specific 5-year survival, excluding cases with DCO, was 10.6% (95% CI: 7.7-13.5); 5-year relative survival rate was 12.3% (95% CI: 9.1-16.1), men 10.9% (95% CI: 7.4-15.2) and women 16.1% (95% CI: 9.5-24.5). Five-year specific survival was higher for patients aged < 55 years (17.3%), with intestinal type of cancer (14.6%), without metastasis (22.2%), tumor size < 4 cm (60.0%), without lymphatic invasion (77.1%), only involvement of the mucous membrane (100%). Statistically significant independent prognostic factors were: TNM staging, diffuse type, metastasis, supraclavicular adenopathy, palpable tumor, and hepatitis or ascites. CONCLUSION: Social determinants are the main risk factors for SC, but not for survival. An advanced clinical stage at consultation is the main cause of poor SC survival.