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A Single Nucleotide Polymorphism in the 5′ Untranslated Region of the EGF Gene Is Associated with Occurrence and Malignant Progression of Gastric CancerHamai Y.a, c · Matsumura S.a · Matsusaki K.e · Kitadai Y.b · Yoshida K.c · Yamaguchi Y.c · Imai K.d · Nakachi K.d · Toge T.c · Yasui W.a
Departments of aMolecular Pathology and bMedicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, cDepartment of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, and dDepartment of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima; eDepartment of Surgery, Hofu Institute of Gastroenterology, Yamaguchi, Japan
Objective: Epidermal growth factor (EGF) has many biological functions and plays an important role in the progression of various tumors including gastric cancer. An A-G single nucleotide polymorphism (SNP) at position 61 in the 5′-untranslated region (UTR) of the EGF gene has recently been reported to be associated with different levels of EGF production. We examined whether this polymorphism is correlated with the development and malignant phenotypes of gastric cancer. Methods: The study population included 200 gastric cancer patients and 230 healthy control subjects. The SNP in the 5′-UTR of the EGF gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results: The A allele was significantly less frequent in patients than in controls (p = 0.01). Individuals with the A/A or A/G genotype showed a significantly lower risk of gastric cancer than those with the G/G genotype [adjusted odds ratio (OR) = 0.56], whereas the same genotypes were associated with malignant progression of this cancer, e.g. deeper tumor invasion, increased lymph node metastasis and advanced clinical stage, and histological classification in gastric cancer patients (adjusted OR = 1.80, 1.98, 2.26 and 1.89, respectively). Conclusions: Our findings suggest that the A-G polymorphism of EGF is involved not only in the occurrence but also in the malignant progression of gastric cancer.
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