title: A single nucleotide polymorphism in the transmembrane domain coding region of HER-2 is associated with development and malignant phenotype of gastric cancer.
abstract: Alterations of the HER-2 (erbB-2/neu) proto-oncogene have been associated with carcinogenesis and poor prognosis of certain cancers. A single nucleotide polymorphism (Ile/Val, A/G) in the transmembrane domain was reported to be associated with a risk of breast cancer. In our study, we examined the association between the HER-2 polymorphism and gastric carcinoma. The Ile/Ile, Ile/Val and Val/Val genotypes were found in 146 (68.9%), 56 (26.4%) and 10 (4.7%) of 212 gastric cancer patients and in 234 (81.5%), 48 (16.7%) and 5 (1.8%) of 287 control subjects, respectively. The Ile/Val or Val/Val genotype was significantly more frequent in patients than in controls (p = 0.005 and 0.033, respectively). The OR of Val/Val genotype then revealed a significantly enhanced risk of 3.25 (95% CI 1.09-9.70) compared to Ile/Ile genotype; heterozygous Ile/Val genotype showed an intermediate risk of 1.97 (1.27-3.06). In patients, carcinomas of advanced stage were significantly more frequent in patients with Ile/Val or Val/Val genotype than those with Ile/Ile genotype (p < 0.001). The logistic regression analysis for tumor invasion, lymph node metastasis and distant metastasis revealed that lymph node metastasis was most closely associated with the HER-2 genotype. These results suggest that this nucleotide polymorphism in the transmembrane domain-coding region of HER-2 could be associated with development of gastric carcinoma and may serve as a predictor of risk for a malignant phenotype of gastric cancer. The association of HER-2 genotype with clinicopathologic characteristics of gastric cancer was also suggested, which has to be confirmed with a larger sample size.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kuraoka
authors.forename: Shunji
authors.initials: S
authors.lastname: Matsumura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hamai
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Kazue
authors.initials: K
authors.lastname: Imai
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsusaki
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Reiko
authors.initials: R
authors.lastname: Ito
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000368:Aged; D016022:Case-Control Studies; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000502:physiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human