Association between common genetic variant of HRH2 and gastric cancer risk

  • Authors:
    • 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
  • View Affiliations

  • Published online on: May 17, 2012     https://doi.org/10.3892/ijo.2012.1482
  • Pages: 497-503
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

August 2012
Volume 41 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Arisawa T, Tahara T, Ozaki K, Matsue Y, Minato T, Yamada H, Nomura T, Hayashi R, Matsunaga K, Fukumura A, Fukumura A, et al: Association between common genetic variant of HRH2 and gastric cancer risk. Int J Oncol 41: 497-503, 2012
APA
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, 497-503. https://doi.org/10.3892/ijo.2012.1482
MLA
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."Association between common genetic variant of HRH2 and gastric cancer risk". International Journal of Oncology 41.2 (2012): 497-503.
Chicago
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."Association between common genetic variant of HRH2 and gastric cancer risk". International Journal of Oncology 41, no. 2 (2012): 497-503. https://doi.org/10.3892/ijo.2012.1482