Association between common genetic variant of HRH2 and gastric cancer risk

Tomiyasu Arisawa, Tomomitsu Tahara, Kazuaki Ozaki, Yasuhiro Matsue, Takahiro Minato, Hideto Yamada, Tomoe Nomura, Ranji Hayashi, Kazuhiro Matsunaga, Atsushi Fukumura, Masakatsu Nakamura, Nobuyuki Toshikuni, Hisakazu Shiroeda, Tomoyuki Shibata

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)497-503
Number of pages7
JournalInternational Journal of Oncology
Volume41
Issue number2
DOIs
Publication statusPublished - 01-08-2012

Fingerprint

Homozygote
Stomach Neoplasms
Pepsinogen C
Pepsinogen A
Stomach
Metaplasia
Atrophy
Alleles
Genotype
Intestinal Neoplasms
Single-Stranded Conformational Polymorphism
Histamine H2 Receptors
Upper Gastrointestinal Tract
Multiplex Polymerase Chain Reaction
Pylorus
Gastritis
Histamine
Endoscopy
Carcinogenesis
Serum

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Arisawa, T., Tahara, T., Ozaki, K., Matsue, Y., Minato, T., Yamada, H., ... Shibata, T. (2012). Association between common genetic variant of HRH2 and gastric cancer risk. International Journal of Oncology, 41(2), 497-503. https://doi.org/10.3892/ijo.2012.1482
Arisawa, Tomiyasu ; Tahara, Tomomitsu ; Ozaki, Kazuaki ; Matsue, Yasuhiro ; Minato, Takahiro ; Yamada, Hideto ; Nomura, Tomoe ; Hayashi, Ranji ; Matsunaga, Kazuhiro ; Fukumura, Atsushi ; Nakamura, Masakatsu ; Toshikuni, Nobuyuki ; Shiroeda, Hisakazu ; Shibata, Tomoyuki. / Association between common genetic variant of HRH2 and gastric cancer risk. In: International Journal of Oncology. 2012 ; Vol. 41, No. 2. pp. 497-503.
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author = "Tomiyasu Arisawa and Tomomitsu Tahara and Kazuaki Ozaki and Yasuhiro Matsue and Takahiro Minato and Hideto Yamada and Tomoe Nomura and Ranji Hayashi and Kazuhiro Matsunaga and Atsushi Fukumura and Masakatsu Nakamura and Nobuyuki Toshikuni and Hisakazu Shiroeda and Tomoyuki Shibata",
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Arisawa, T, Tahara, T, Ozaki, K, Matsue, Y, Minato, T, Yamada, H, Nomura, T, Hayashi, R, Matsunaga, K, Fukumura, A, Nakamura, M, Toshikuni, N, Shiroeda, H & Shibata, T 2012, 'Association between common genetic variant of HRH2 and gastric cancer risk', International Journal of Oncology, vol. 41, no. 2, pp. 497-503. https://doi.org/10.3892/ijo.2012.1482

Association between common genetic variant of HRH2 and gastric cancer risk. / Arisawa, Tomiyasu; Tahara, Tomomitsu; Ozaki, Kazuaki; Matsue, Yasuhiro; Minato, Takahiro; Yamada, Hideto; Nomura, Tomoe; Hayashi, Ranji; Matsunaga, Kazuhiro; Fukumura, Atsushi; Nakamura, Masakatsu; Toshikuni, Nobuyuki; Shiroeda, Hisakazu; Shibata, Tomoyuki.

In: International Journal of Oncology, Vol. 41, No. 2, 01.08.2012, p. 497-503.

Research output: Contribution to journalArticle

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T1 - Association between common genetic variant of HRH2 and gastric cancer risk

AU - Arisawa, Tomiyasu

AU - Tahara, Tomomitsu

AU - Ozaki, Kazuaki

AU - Matsue, Yasuhiro

AU - Minato, Takahiro

AU - Yamada, Hideto

AU - Nomura, Tomoe

AU - Hayashi, Ranji

AU - Matsunaga, Kazuhiro

AU - Fukumura, Atsushi

AU - Nakamura, Masakatsu

AU - Toshikuni, Nobuyuki

AU - Shiroeda, Hisakazu

AU - Shibata, Tomoyuki

PY - 2012/8/1

Y1 - 2012/8/1

N2 - 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.

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