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Prognostic impact of FOXF1 polymorphisms in gastric cancer patients

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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.

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Acknowledgements

Satoshi Matsusaka is a recipient of Takashi Tsuruo Memorial Fund. Stefan Stremitzer is a recipient of an Erwin Schrödinger fellowship of the Austrian Science Fund (J3501-B13). Martin D. Berger received a grant from the Swiss Cancer League (BIL KLS-3334-02-2014). The project described was supported in part by Award Number P30CA014089 from the National Cancer Institute.

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The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. This project was also supported in part by the San Pedro Guild Foundation.

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Authors and Affiliations

  1. Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    S Matsusaka, S Cao, D L Hanna, D Yang, W Zhang, Y Ning, S Stintzing, A Sebio, Y Sunakawa, S Stremitzer, S Yamauchi, S Okazaki, M D Berger, A Parekh, Y Miyamoto & H-J Lenz

  2. Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    A H Wu

  3. Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan

    K Chin & N Mizunuma

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  1. S Matsusaka
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  2. A H Wu
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  3. S Cao
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  4. D L Hanna
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  5. K Chin
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  6. D Yang
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  7. W Zhang
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  8. Y Ning
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  9. S Stintzing
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  10. A Sebio
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  11. Y Sunakawa
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  12. S Stremitzer
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  13. S Yamauchi
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  14. S Okazaki
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  15. M D Berger
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  16. A Parekh
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  17. Y Miyamoto
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  18. N Mizunuma
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  19. H-J Lenz
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Correspondence to H-J Lenz.

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Additional information

Presented in part at the American Society of Clinical Oncology Annual Meeting, 29 May–2 June, 2015, Chicago, IL, USA.

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Cite this article

Matsusaka, S., Wu, A., Cao, S. et al. Prognostic impact of FOXF1 polymorphisms in gastric cancer patients. Pharmacogenomics J 18, 262–269 (2018). https://doi.org/10.1038/tpj.2017.9

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