title: Pancreatic cancer: Helicobacter pylori colonization, N-nitrosamine exposures, and ABO blood group.
abstract: Thirty years of research with animal models has shown that pancreatic adenocarcinoma is induced by N-nitrosamine carcinogens, which damage DNA through adduct formation. Human risk factors for pancreatic cancer include gastric colonization by Helicobacter pylori, as well as dietary intake of those same N-nitrosamines or of nitrite which forms those N-nitrosamines in the stomach, and cigarette smoking which also contains those N-nitrosamines. Physiologic actions of H. pylori colonization enhance the carcinogenic effect of N-nitrosamines delivered by smoking or dietary sources. This effect is modulated by host inflammatory response to the organism, by various virulence and other properties of the Helicobacter itself, and by host-organism interactions. A recent genome-wide association study identified SNPs within the ABO 9q34 locus as statistically significantly associated with risk of pancreatic cancer. A number of recent and older studies going back 40 yr also support the ABO association. ABO-product antigens are expressed on gastrointestinal epithelium on which H. pylori binds, and ABO genotype is known to be associated with risks of duodenal and gastric ulcer and with risk of gastric cancer, conditions definitively related to Helicobacter colonization. We suspect that ABO genotype/phenotype status influences the behavior of H. pylori which in turn affects gastric and pancreatic secretory function, and these ultimately influence the pancreatic carcinogenicity of dietary- and smoking-related N-nitrosamine exposures, and thus risk of pancreatic cancer. Our study results on the interaction of ABO and H. pylori significantly confirm this hypothesis and together with other existing studies strongly implicate this organism in the disease etiology.
authors.affiliation: Department of Epidemiology and Public Health, Yale University, School of Public Health, School of Medicine, New Haven, Connecticut 06520-8034, USA.
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000230:Adenocarcinoma / Q000097:blood / Q000139:chemically induced / Q000209:etiology* / Q000382:microbiology; D005260:Female; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000139:chemically induced / Q000209:etiology* / Q000382:microbiology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013270:Stomach / Q000382:microbiology*
chemical_list: D000017:ABO Blood-Group System; D009602:Nitrosamines