Prognostic impact of FOXF1 polymorphisms in gastric cancer patients

Pharmacogenomics J. 2018 Apr;18(2):262-269. doi: 10.1038/tpj.2017.9. Epub 2017 Apr 11.

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • California / epidemiology
  • Case-Control Studies
  • Female
  • Forkhead Transcription Factors / genetics*
  • Genome-Wide Association Study / methods
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Retrospective Studies
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / genetics*
  • Young Adult

Substances

  • FOXF1 protein, human
  • Forkhead Transcription Factors