title: Prognostic role of lemur tyrosine kinase-3 germline polymorphisms in adjuvant gastric cancer in Japan and the United States.
abstract: Lemur tyrosine kinase-3 (LMTK3) was recently identified as an estrogen receptor (ER)-α modulator related to endocrine therapy resistance, and its polymorphisms rs9989661 (T>C) T/T genotype and rs8108419 (G>A) G/G or A/G genotype predicted improved outcomes in breast cancer. Because different predominant ER distributions link to breast and gastric cancer and little is known of the prognostic role of LMTK3 in gastric cancer, this study was carried out to clarify the prognostic role of these polymorphisms in gastric cancer. One-hundred and sixty-nine Japanese and 137 U.S. patients with localized gastric adenocarcinoma were enrolled. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA sequencing. Overall, these polymorphisms were not associated with survival in both cohorts. When gender was considered, in multivariate analysis, harboring rs9989661 T/T genotype was associated with disease-free survival [HR, 4.37; 95% confidence interval (CI), 2.08-9.18; P < 0.0001] and overall survival (OS; HR, 3.69; 95% CI, 1.65-8.24; P = 0.0014) in the Japanese males and time to recurrence (HR, 7.29; 95% CI, 1.07-49.80; P = 0.043) in the U.S. females. Meanwhile, harboring rs8108419 G/G genotype was associated with OS in the Japanese females (HR, 3.04; 95% CI, 1.08-8.56; P = 0.035) and the U.S. males (HR, 3.39; 95% CI, 1.31-8.80; P = 0.012). The prognostic role of these polymorphisms may be negative in gastric cancer. These findings suggest that the estrogen pathway may play a prognostic role in patients with gastric cancer but this may be dependent on the regional differences both in physiology and genetic alterations of gastric cancer.
authors.affiliation: Corresponding Author: Heinz-Josef Lenz, Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, 1441 Eastlake Avenue, Los Angeles, CA 90033. lenz@usc.edu.
authors.forename: Takeru
authors.initials: T
authors.lastname: Wakatsuki
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: LaBonte
authors.forename: Pierre O
authors.initials: PO
authors.lastname: Bohanes
authors.forename: Wu
authors.initials: W
authors.lastname: Zhang
authors.forename: Dongyun
authors.initials: D
authors.lastname: Yang
authors.forename: Mizutomo
authors.initials: M
authors.lastname: Azuma
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Barzi
authors.forename: Yan
authors.initials: Y
authors.lastname: Ning
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.forename: Siamak
authors.initials: S
authors.lastname: Saadat
authors.forename: Nico
authors.initials: N
authors.lastname: Volz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stintzing
authors.forename: Rita
authors.initials: R
authors.lastname: El-Khoueiry
authors.forename: Wasaburo
authors.initials: W
authors.lastname: Koizumi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Manish
authors.initials: M
authors.lastname: Shah
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Georgios
authors.initials: G
authors.lastname: Giamas
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; C560359:LMTK3 protein, human; D017346:Protein Serine-Threonine Kinases
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