title: Prognostic impact of FOXF1 polymorphisms in gastric cancer patients.
abstract: A recent genome-wide association study identified seven single-nucleotide polymorphisms (SNPs) in region 16q24, near the Forkhead box-F1 (FOXF1) gene, which confer susceptibility to esophageal adenocarcinoma. We examined whether these SNPs are associated with clinical outcomes in gastric cancer (GC) patients in Japan and the United States. A total of 362 patients were included in this study: 151 Japanese GC patients treated with first-line S1 plus CDDP (training cohort) and 211 GC patients from Los Angeles County (LAC; validation cohort). Genomic DNA was isolated from whole blood or tumor tissue and analyzed by PCR-based direct DNA sequencing. Cox proportional hazard regression analyses were used to assess relationships between FOXF1 SNPs and progression-free survival (PFS) and overall survival (OS). FOXF1 rs3950627 was significantly associated with survival in both the training and validation cohorts. Japanese patients with the C/C genotype had a longer PFS (median 8.2 vs 5.3 months, hazard ratio (HR) 1.44, P=0.037) and OS (median 16.4 vs 12.2 months, HR 1.44, P=0.043) compared to patients with any A allele. Similarly, LAC patients with the C/C genotype had improved OS (3.9 vs 2.3 years, HR 1.5, P=0.022). Subgroup analyses showed these associations were specific to male patients and primary tumor subsite. Our findings suggest that FOXF1 rs3950627 might be a promising prognostic marker in GC patients.
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Matsusaka
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Wu
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cao
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Hanna
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Chin
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Stintzing
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sebio
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sunakawa
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Stremitzer
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yamauchi
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Okazaki
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Berger
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Parekh
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Mizunuma
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: C098521:FOXF1 protein, human; D051858:Forkhead Transcription Factors