Association between receptor interacting serine/threonine kinase 2 polymorphisms and gastric cancer susceptibility

Masafumi Ota, Tomomitsu Tahara, Toshimi Otsuka, Wu Jing, Tomoe Nomura, Ranji Hayashi, Takeo Shimasaki, Masakatsu Nakamura, Tomoyuki Shibata, Tomiyasu Arisawa

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The present study aimed to investigate whether single nucleotide polymorphisms in receptor interacting serine/threonine kinase 2 (RIPK2), which encodes a component of the nucleotide binding oligomerization domain containing 2-RIP2 pathway, may compromise the innate immune response to Helicobacter pylori infection, leading to increased susceptibility to gastric cancer in the Japanese population. The present case control study investigated the associations between RIPK2 single nucleotide polymorphisms and gastric mucosal inflammation, atrophy and cancer susceptibility in 528 patients with gastric cancer and 697 patients without gastric malignancies on upper gastro-duodenal endoscopy. Overall, the RIPK2 rs16900627 minor allele was significantly associated with the susceptibility to gastric cancer [OR, 1.37; 95% confidence interval (CI), 1.06-1.77; P=0.016], particularly of the intestinal type (OR, 1.53; 95% CI, 1.13-2.07; P=0.0062). It was also significantly associated with gastric mucosal atrophy (OR, 1.83; 95% CI, 1.14-2.93; P=0.011). When assessing the severity of chronic gastritis using the updated Sydney system, the activity and inflammation scores, as well as atrophy and metaplasia scores, were significantly higher in rs16900627 minor allele carriers compared with wild-type homozygotes. In patients younger than 60 years old, the pepsinogen I/II ratio was significantly lower in rs16900627 minor allele carriers compared with wild-type homozygotes (P=0.037). The rs16900627 minor allele is associated with the severity of gastric mucosal inflammation and the development of gastric mucosal atrophy. Carriers of this allele may have an increased risk for the development of gastric cancer, particularly of the intestinal type.

Original languageEnglish
Pages (from-to)3772-3778
Number of pages7
JournalOncology Letters
Volume15
Issue number3
DOIs
Publication statusPublished - 03-2018

Fingerprint

Receptor-Interacting Protein Serine-Threonine Kinase 2
Stomach Neoplasms
Stomach
Alleles
Atrophy
Homozygote
Confidence Intervals
Inflammation
Single Nucleotide Polymorphism
Pepsinogen C
Pepsinogen A
Metaplasia
Helicobacter Infections
Gastritis
Innate Immunity
Helicobacter pylori
Endoscopy
Case-Control Studies
Neoplasms
Nucleotides

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ota, Masafumi ; Tahara, Tomomitsu ; Otsuka, Toshimi ; Jing, Wu ; Nomura, Tomoe ; Hayashi, Ranji ; Shimasaki, Takeo ; Nakamura, Masakatsu ; Shibata, Tomoyuki ; Arisawa, Tomiyasu. / Association between receptor interacting serine/threonine kinase 2 polymorphisms and gastric cancer susceptibility. In: Oncology Letters. 2018 ; Vol. 15, No. 3. pp. 3772-3778.
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abstract = "The present study aimed to investigate whether single nucleotide polymorphisms in receptor interacting serine/threonine kinase 2 (RIPK2), which encodes a component of the nucleotide binding oligomerization domain containing 2-RIP2 pathway, may compromise the innate immune response to Helicobacter pylori infection, leading to increased susceptibility to gastric cancer in the Japanese population. The present case control study investigated the associations between RIPK2 single nucleotide polymorphisms and gastric mucosal inflammation, atrophy and cancer susceptibility in 528 patients with gastric cancer and 697 patients without gastric malignancies on upper gastro-duodenal endoscopy. Overall, the RIPK2 rs16900627 minor allele was significantly associated with the susceptibility to gastric cancer [OR, 1.37; 95{\%} confidence interval (CI), 1.06-1.77; P=0.016], particularly of the intestinal type (OR, 1.53; 95{\%} CI, 1.13-2.07; P=0.0062). It was also significantly associated with gastric mucosal atrophy (OR, 1.83; 95{\%} CI, 1.14-2.93; P=0.011). When assessing the severity of chronic gastritis using the updated Sydney system, the activity and inflammation scores, as well as atrophy and metaplasia scores, were significantly higher in rs16900627 minor allele carriers compared with wild-type homozygotes. In patients younger than 60 years old, the pepsinogen I/II ratio was significantly lower in rs16900627 minor allele carriers compared with wild-type homozygotes (P=0.037). The rs16900627 minor allele is associated with the severity of gastric mucosal inflammation and the development of gastric mucosal atrophy. Carriers of this allele may have an increased risk for the development of gastric cancer, particularly of the intestinal type.",
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Ota, M, Tahara, T, Otsuka, T, Jing, W, Nomura, T, Hayashi, R, Shimasaki, T, Nakamura, M, Shibata, T & Arisawa, T 2018, 'Association between receptor interacting serine/threonine kinase 2 polymorphisms and gastric cancer susceptibility', Oncology Letters, vol. 15, no. 3, pp. 3772-3778. https://doi.org/10.3892/ol.2018.7785

Association between receptor interacting serine/threonine kinase 2 polymorphisms and gastric cancer susceptibility. / Ota, Masafumi; Tahara, Tomomitsu; Otsuka, Toshimi; Jing, Wu; Nomura, Tomoe; Hayashi, Ranji; Shimasaki, Takeo; Nakamura, Masakatsu; Shibata, Tomoyuki; Arisawa, Tomiyasu.

In: Oncology Letters, Vol. 15, No. 3, 03.2018, p. 3772-3778.

Research output: Contribution to journalArticle

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AU - Ota, Masafumi

AU - Tahara, Tomomitsu

AU - Otsuka, Toshimi

AU - Jing, Wu

AU - Nomura, Tomoe

AU - Hayashi, Ranji

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AU - Arisawa, Tomiyasu

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