Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study.
ABSTRACT BACKGROUND: Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer. OBJECTIVE: We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study. DESIGN: A total of 120,852 men and women aged 55-69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adenocarcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis. RESULTS: Positive associations were observed between N-nitrosodimethylamine intake and ESCC risk (HR for 0.1-μg/d increase in intake: 1.15; 95% CI: 1.05, 1.25; P-trend = 0.01 based on tertiles of intake) and GNCA risk (1.06; 95% CI: 1.01, 1.10; P-trend = 0.09) in men. ESCC risk was associated with nitrite intake (HR for 0.1-mg/d increase: 1.19; 95% CI: 1.05, 1.36; P-trend = 0.06) and heme-iron intake (HR for 1-mg/d increase: 1.83; 95% CI: 0.98, 3.39; P-trend = 0.03). Among women, exposure levels were lower, and we found no convincing positive associations. CONCLUSION: These results suggest that N-nitroso compounds may influence the risk of ESCC in men, but there are no clear associations for other esophageal and gastric subtypes.
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ABSTRACT: Over the last 3 decades, the incidence of esophageal adenocarcinoma has dramatically increased in Western countries; a similar increase may be observed in Asian countries in the near future. Esophageal adenocarcinoma arises from a sequential gastroesophageal reflux disease (GERD) spectrum from reflux erosive esophagitis, to Barrett's esophagus, and finally to esophageal adenocarcinoma. At present, gastric acid and bile are assumed to be primarily involved in the etiology of the GERD spectrum. We reported in 2002 that, at the gastroesophageal junction in humans, abundant amounts of nitric oxide (NO) are generated luminally through the entero-salivary re-circulation of dietary nitrate. Since then, we have carried out a series of experiments to demonstrate that NO diffuses into the adjacent epithelium at cytotoxic levels. This diffusion results in disruption of the epithelial barrier function, exacerbation of inflammation, acceleration of columnar transformation in the esophagus (Barrett's esophagus) via the induction of caudal-type homeobox 2, and the shifting of carcinogenic N-nitroso compound formation from the luminal to epithelial compartment. These results suggest that, in addition to conventionally recognized causative factors, luminal NO could also be involved in the pathogenesis of the GERD spectrum. In addition, we recently showed that there is a prominent gender-related difference in NO-related cytotoxicity in the esophagus and that estrogen attenuated the esophageal tissue damage via the estrogen receptor in female rats. The role of estrogen in attenuating the esophageal tissue damage in NO-related esophageal damage could explain the well-recognized male predominance in the GERD spectrum in humans.Journal of Gastroenterology and Hepatology 05/2014; 29(5):898-905. · 3.33 Impact Factor
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ABSTRACT: Humans depend on our commensal bacteria for nutritive, immune-modulating, and metabolic contributions to maintenance of health. However, this commensal community exists in careful balance that, if disrupted, enters dysbiosis; this has been shown to contribute to the pathogenesis of colon, gastric, esophageal, pancreatic, laryngeal, breast, and gallbladder carcinomas. This development is closely tied to host inflammation, which causes and is aggravated by microbial dysbiosis and increases vulnerability to pathogens. Advances in sequencing technology have increased our ability to catalog microbial species associated with various cancer types across the body. However, defining microbial biomarkers as cancer predictors presents multiple challenges, and existing studies identifying cancer-associated bacteria have reported inconsistent outcomes. Combining metabolites and microbiome analyses can help elucidate interactions between gut microbiota, metabolism, and the host. Ultimately, understanding how gut dysbiosis impacts host response and inflammation will be critical to creating an accurate picture of the role of the microbiome in cancer.Current Oncology Reports 10/2014; 16(10):406. · 3.33 Impact Factor
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ABSTRACT: A multifactorial and multistep model of gastric cancer (GC) is currently accepted, according to which different environmental and genetic factors are involved at different stages in the cancer process. The aim of this article is to review the most relevant information published on the relative contribution of genetic and environmental factors. Large meta-analyses confirmed the association between IL8, IL10, TNF-b, TP53 and PSCA, while genetic variation at different genes such as XPG, PLCE1, HFE, ERCC5, EZH2, DOC2, CYP19A1, ALDH2, and CDH1 have been reported to be associated with GC risk. Several microRNAs have also been associated with GC and their prognosis. Cohort studies have shown the association between GC and fruit, flavonoid, total antioxidant capacity, and green tea intake. Obesity was associated with cardia GC, heme iron intake from meat with GC risk. Several large meta-analyses have confirmed the positive association of GC with salt intake and pickled foods and the negative association with aspirin use.Helicobacter 09/2013; 18(s1). · 3.51 Impact Factor