Serologic Profile of Antiparietal Cell Antibodies, Pepsinogens, and H. pylori and Risk of Upper Gastrointestinal Cancer: A Nested Case-Control Study in China.

BACKGROUND: Autoimmune gastritis is understudied and possibly associated with gastric noncardia adenocarcinoma (GNCA) and esophageal squamous cell carcinoma (ESCC) in Western populations when it presents as pernicious anemia. METHODS: A nested case-control study within a Chinese cohort included 100 ESCC, 200 gastric cardia adenocarcinoma (GCA), and 200 GNCA cases diagnosed between 1986 and 2001 and 400 controls. Serostatus of antiparietal cell antibodies (APCA), Helicobacter pylori antibodies, and pepsinogens were measured using commercial kits and serum collected at baseline. We used logistic regression to calculate odds ratios (OR) and 95% confidence interval (CI) for associations between serologic biomarkers and cancer risk adjusted for numerous potential confounders. RESULTS: There was an average interval of 8 years between baseline blood draw and cancer diagnosis. The baseline prevalence of APCA seropositivity was 10.0% and 14.5% in subjects who developed GCA and GNCA, respectively. APCA seropositivity was inversely associated with later development of GCA (OR = 0.42; 95% CI, 0.24-0.75), but not significantly associated with later development of GNCA (OR = 0.82; 95% CI, 0.50-1.36) or ESCC (OR = 1.05; 95% CI, 0.58-1.88). APCA seropositivity was significantly associated with low pepsinogen I/II ratios (OR = 3.69; 95% CI, 1.66-8.21), and individuals with low pepsinogen I/II ratios who were seronegative for APCA had the highest risk of both GCA and GNCA. CONCLUSIONS: APCA seropositivity measured years prior to diagnosis was associated with prevalent atrophic gastritis but inversely associated with incident GCA in this Chinese population. IMPACT: APCA may contribute to a growing list of serologic markers that can improve risk stratification for gastric cancer.

Effects of Nutrition Intervention on Total and Cancer Mortality: 25-Year Post-trial Follow-up of the 5.25-Year Linxian Nutrition Intervention Trial.

Background: A beneficial effect of supplementation with selenium, vitamin E, and beta-carotene was observed on total and cancer mortality in a Chinese population, and it endured for 10 years postintervention, but longer durability is unknown. Methods: A randomized, double-blind, placebo-controlled trial was conducted in Linxian, China, from 1986 to 1991; 29 584 residents age 40 to 69 years received daily supplementations based on a factorial design: Factors A (retinol/zinc), B (riboflavin/niacin), C (vitamin C/molybdenum), and/or D (selenium/vitamin E/beta-carotene), or placebo for 5.25 years, and followed for up 25 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the intervention effects on mortalities were estimated using Cox proportional hazards models. Results: Through 2016, the interventions showed no effect on total mortality. The previously reported protective effect of Factor D against total mortality was lost 10 years postintervention. The protective effect of Factor D for gastric cancer was attenuated (HR = 0.93, 95% CI = 0.85 to 1.01), but a newly apparent protective effect against esophageal cancer was found for Factor B (HR = 0.92, 95% CI = 0.85 to 1.00, two-sided P = .04). Other protective/adverse associations were observed for cause-specific mortalities. Protective effects were found in people younger than age 55 years at baseline against non-upper gastrointestinal cancer death for Factor A (HR = 0.80, 95% CI = 0.69 to 0.92) and against death from stroke for Factor C (HR = 0.89, 95% CI = 0.82 to 0.96). In contrast, increased risk of esophageal cancer was found when the intervention began after age 55 years for Factors C (HR = 1.16, 95% CI = 1.04 to 1.30) and D (HR = 1.20, 95% CI = 1.07 to 1.34). Conclusions: Multiyear nutrition intervention is unlikely to have a meaningful effect on mortality more than a decade after supplementation ends, even in a nutritionally deprived population. Whether sustained or repeat intervention would provide longer effects needs further investigation.

Cross sectional study of serum selenium concentration and esophageal squamous dysplasia in western Kenya.

BACKGROUND: Low serum selenium status has been associated with increased risk of esophageal squamous cell carcinoma (ESCC). East Africa is a region of high ESCC incidence and is known to have low soil selenium levels, but this association has not previously been evaluated. In this study we assessed the association of serum selenium concentration and the prevalence of esophageal squamous dysplasia (ESD), the precursor lesion of ESCC, in a cross-sectional study of subjects from Bomet, Kenya. METHODS: 294 asymptomatic adult residents of Bomet, Kenya completed questionnaires and underwent endoscopy with Lugol's iodine staining and biopsy for detection of ESD. Serum selenium concentrations were measured by instrumental neutron activation analysis. Odds ratios (OR) and confidence intervals (95% CI) for associations between serum selenium and ESD were calculated using unconditional logistic regression. RESULTS: The mean serum selenium concentration was 85.5 (±28.3) µg/L. Forty-two ESD cases were identified (14% of those screened), including 5 (12%) in selenium quartile 1 (Q1), 5 (12%) in Q2, 15 (36%) in Q3, and 17 (40%) in Q4. Higher serum selenium was associated with prevalence of ESD (Q4 vs Q1: OR: 3.03; 95% CI: 1.05-8.74) and this association remained after adjusting for potential confounders (Q4 vs Q1: OR: 3.87; 95% CI: 1.06-14.19). CONCLUSION: This is the first study to evaluate the association of serum selenium concentration and esophageal squamous dysplasia in an African population at high risk for ESCC. We found a positive association between higher serum selenium concentration and prevalence of ESD, an association contrary to our original hypothesis. Further work is needed to better understand the role of selenium in the etiology of ESCC in this region, and to develop effective ESCC prevention and control strategies.