title: Association between common genetic variant of HRH2 and gastric cancer             risk.
abstract: Histamine plays important physiological roles in the upper gastrointestinal             tract and acts via the H2 receptor. The -1018 G>A (rs2067474) in an enhancer             element of the promoter and non-synonymous rs79385261 (Asn46Thr) were identified             in HRH2. We attempted to clarify the associations of these polymorphisms with             gastric carcinogenesis. The study was performed in 321 patients with gastric cancer             and 599 subjects with no evidence of gastric malignancies on upper gastroduodenal             endoscopy. The genotypes were determined using a one-tube multiplex PCR-SSCP method.             The degree of gastritis was assessed in 496 subjects and serum pepsinogen (PG)             I/II levels were measured in 124 subjects without gastric cancer. The minor allele             of Asn46Thr could not be detected. The frequencies of the -1018 A allele in the             non-GC and GC groups were 13.5% and 8.26%, respectively (p=0.00077). Overall,             -1018 GG homozygotes had an increased risk for developing gastric cancer (OR 1.68;             95% CI 1.17-2.42; p=0.0052), especially intestinal type cancer (OR 1.94; 95% CI             1.23-3.08; p=0.0047). In subjects aged >60 years, the adjusted risk for gastric             cancer among individuals who were -1018 GG homozygotes was 1.87 (range 1.19-2.93;             p=0.0065) compared with A carriers. In the gastric cancer cases located in the             antrum and at comparative advanced stage, -1018 GG homozygosity was a significantly             increased risk factor. In subjects >60 years, the metaplasia score was significantly             higher in -1018 GG homozygotes than A carriers. Both atrophy and metaplasia scores             were significantly increased with age only in -1018 GG homozygotes. The PG I/II             ratio was significantly decreased in H. pylori positive GG homozygotes than negative             GG homozygotes and positive A carriers. Our results suggest that -1018 GG homozygosity             of HRH2 may be associated with the severity of gastric mucosal atrophy. This genotype             has an increased risk for the subsequent development of gastric cancer, especially             intestinal type, at advanced age.
authors.affiliation: Department of Gastroenterology, Kanazawa Medical University, Uchinada-machi, Ishikawa, Japan. tarisawa@kanazawa-med.ac.jp
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ozaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsue
authors.forename: Takahiro
authors.initials: T
authors.lastname: Minato
authors.forename: Hideto
authors.initials: H
authors.lastname: Yamada
authors.forename: Tomoe
authors.initials: T
authors.lastname: Nomura
authors.forename: Ranji
authors.initials: R
authors.lastname: Hayashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukumura
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Toshikuni
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Shiroeda
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
mesh_terms: D000368:Aged; D005260:Female; D005756:Gastritis / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D011970:Receptors, Histamine H2 / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics* / Q000382:microbiology
chemical_list: D011970:Receptors, Histamine H2; D020116:Pepsinogen A