Prognostic impact of FOXF1 polymorphisms in gastric cancer patients

Matsusaka, S; Wu, A H; Cao, S; Hanna, D L; Chin, K; Yang, D; Zhang-Wu, Xiaxia; Ning, Y; Stintzing, S; Sebio, A; Sunakawa, Y; Stremitzer, S; Yamauchi, S; Okazaki, S; Berger, Martin Dave; Parekh, A; Miyamoto, Y; Mizunuma, N; Lenz, H-J (2018). Prognostic impact of FOXF1 polymorphisms in gastric cancer patients. Pharmacogenomics journal, 18(2), pp. 262-269. Nature Publishing Group 10.1038/tpj.2017.9

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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.The Pharmacogenomics Journal advance online publication, 11 April 2017; doi:10.1038/tpj.2017.9.

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