Functional promoter polymorphisms of NFKB1 influence susceptibility to the diffuse type of gastric cancer

Arisawa,Tomiyasu; Tahara,Tomomitsu; Shiroeda,Hisakazu; Yamada,Kaho; Nomura,Tomoe; Yamada,Hideto; Hayashi,Ranji; Matsunaga,Kazuhiro; Otsuka,Toshimi; Nakamura,Masakatsu; Shimasaki,Takeo; Toshikuni,Nobuyuki; Kawada,Natsuko; Shibata,Tomoyuki

doi:10.3892/or.2013.2768

Functional promoter polymorphisms of NFKB1 influence susceptibility to the diffuse type of gastric cancer

Authors:
- Tomiyasu Arisawa
- Tomomitsu Tahara
- Hisakazu Shiroeda
- Kaho Yamada
- Tomoe Nomura
- Hideto Yamada
- Ranji Hayashi
- Kazuhiro Matsunaga
- Toshimi Otsuka
- Masakatsu Nakamura
- Takeo Shimasaki
- Nobuyuki Toshikuni
- Natsuko Kawada
- Tomoyuki Shibata
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Affiliations: Department of Gastroenterology, Kanazawa Medical University, Uchinada-machi, Ishikawa 920-029, Japan, Department of Gastroenterology, Fujita Health University, Kutsukake-cho, Toyoake 470-1192, Japan
Published online on: October 1, 2013 https://doi.org/10.3892/or.2013.2768
Pages: 3013-3019

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Abstract

In the present study, we report an association between gastric cancer and polymorphisms in NFKB1 (rs28362941 and rs78696119). We employed the PCR-SSCP method to detect gene polymorphisms in 479 gastric cancer cases and 880 controls. The rs28362941 del/del homozygote was significantly associated with gastric cancer development; in particular it was closely associated with diffuse type gastric cancer. The rs78696119 GG homozygote was also associated with the diffuse type of gastric cancer. In young subjects, both polymorphisms were significantly associated with the development of gastric cancer. In addition, both polymorphisms were related to tumor progression such as tumor invasion and lymph node metastasis. The inflammatory cell infiltration into non-cancerous gastric mucosa was greater in the subjects with the rs28362491 del/del or rs78696119 GG genotype when compared to those with the other genotypes. In conclusion, functional polymorphisms of NFKB1 are associated with an increased risk of gastric cancer; in particular they are closely associated with the development of diffuse type of gastric cancer via severe gastric inflammation. These polymorphisms also appear to be associated with gastric cancer progression.

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