Single‑nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk

Enokida,Yasuaki; Shimizu,Kimihiro; Kakegawa,Seiichi; Atsumi,Jun; Takase,Yoshiaki; Miyamae,Yohei; Nagashima,Toshiteru; Ohtaki,Yoichi; Kaira,Kyoichi; Sunaga,Noriaki; Yanagitani,Noriko; Yoshino,Reiko; Tsunekawa,Katsuhiko; Igai,Hitoshi; Kamiyoshihara,Mitsuhiro; Usui,Kengo; Lezhava,Alexander; Tomizawa,Yoshio; Ishikawa,Toshihisa; Murakami,Masami; Hayashizaki,Yoshihide; Takeyoshi,Izumi

doi:10.3892/br.2014.305

Single‑nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk

Authors:
- Yasuaki Enokida
- Kimihiro Shimizu
- Seiichi Kakegawa
- Jun Atsumi
- Yoshiaki Takase
- Yohei Miyamae
- Toshiteru Nagashima
- Yoichi Ohtaki
- Kyoichi Kaira
- Noriaki Sunaga
- Noriko Yanagitani
- Reiko Yoshino
- Katsuhiko Tsunekawa
- Hitoshi Igai
- Mitsuhiro Kamiyoshihara
- Kengo Usui
- Alexander Lezhava
- Yoshio Tomizawa
- Toshihisa Ishikawa
- Masami Murakami
- Yoshihide Hayashizaki
- Izumi Takeyoshi
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Affiliations: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of Internal Medicine, National Hospital Organization Nishi‑Gunma Hospital, Shibukawa, Gunma 377‑8511, Japan, Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of General Thoracic Surgery, Maebashi Red Cross Hospital, Maebashi, Gunma 371‑0014, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230‑0045, Japan, NGO Personalized Medicine and Healthcare, Yokohama, Kanagawa 226‑0016, Japan, RIKEN Preventive Medicine and Diagnosis Innovation Program, Yokohama, Kanagawa 230‑0045, Japan
Published online on: June 26, 2014 https://doi.org/10.3892/br.2014.305
Pages: 719-724

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Abstract

Murine double minute 2 (MDM2) is a negative regulator of p53. A single‑nucleotide polymorphism (SNP) (rs2279744: c.309T>G) in the promoter region of the MDM2 gene has been shown to result in higher levels of MDM2 RNA and protein. Regarding the contribution of c.309T>G in the MDM2 gene to the lung cancer risk, previous studies are conflicting. In order to evaluate the association between c.309T>G and the lung cancer risk, a case‑control study was performed. The MDM2 genotypes were determined in 762 lung cancer patients and in 700 cancer‑free control subjects using the Smart Amplification Process. Statistical adjustment was performed for gender, age and pack‑years of smoking. The distributions of c.309T>G (T/T, T/G, G/G) were 20.1, 49.7, 30.2% in the case group and 21.7, 47.9, 30.4% in the healthy‑control group. There were no overall associations between the MDM2 genotypes and the risk of lung cancer [T/G genotype: Adjusted odds ratio (AOR), 1.30; 95% confidence interval (CI), 0.88‑1.93; and G/G genotype: AOR, 1.18; 95% CI, 0.78‑1.80]. The subgroup analysis of gender, histology, smoking status and epidermal growth factor receptor mutation status also indicated that there was no association with lung cancer. Additionally, the genotypes did not have an effect on the age at the time of diagnosis of lung cancer (P=0.25). In conclusion, the G allele frequency in the lung cancer cases was 0.551, which was similar to other studies. The results of the present study suggest that the c.309T>G is not significantly associated with lung cancer.

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