Original Article | Published:

CXCR4 polymorphism predicts progression-free survival in metastatic colorectal cancer patients treated with first-line bevacizumab-based chemotherapy

The Pharmacogenomics Journal volume 17, pages 543550 (2017) | Download Citation

Abstract

We analyzed associations between CXCR4/CXCL12 single-nucleotide polymorphisms and outcomes in metastatic colorectal cancer (mCRC) patients who underwent first-line bevacizumab-based chemotherapy. A total of 874 patients were included in this study: 144 treated with bevacizumab and FOLFOX or XELOX (training cohort), 653 treated with bevacizumab and FOLFIRI or FOLFOXIRI (validation cohort A or B) and 77 treated with cetuximab- and oxaliplatin-based regimens (control cohort). One CXCR4 polymorphism (rs2228014) and two CXCL12 polymorphisms (rs1801157 and rs3740085) were analyzed by PCR-based direct sequencing. Patients with a C/C genotype had a prolonged progression-free survival (PFS) compared with those with any T allele (P=0.030) in the training cohort. Similarly, patients with the C/C genotype had a superior PFS in the validation cohorts, but not in the control cohort. Our findings suggest that a common genetic variant, CXCR4 rs2228014, could predict PFS and may guide therapeutic decisions in mCRC patients receiving first-line bevacizumab-based chemotherapy.

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Acknowledgements

S Matsusaka is a recipient of Takashi Tsuruo Memorial Fund. MD Berger received a grant from the Swiss Cancer League (BIL KLS-3334-02-2014). S Stremitzer is a recipient of an Erwin Schrödinger fellowship of the Austrian Science Fund (J3501-B13). This study was partly funded by NIH Grant P30CA14089-27S1 and Yvonne Bogdanovich. 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.

Author information

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
    • , Y Sunakawa
    • , W Zhang
    • , D Yang
    • , Y Ning
    • , S Stintzing
    • , A Sebio
    • , S Stremitzer
    • , S Yamauchi
    • , A Parekh
    • , S Okazaki
    • , M D Berger
    • , R El-Khoueiry
    • , A Mendez
    •  & H-J Lenz
  2. Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan

    • M Ueno
  3. Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan

    • N Mizunuma
  4. Division of Medical Oncology, Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan

    • W Ichikawa
  5. Azienda Ospedaliero-Universitaria Pisana, Institute Toscano Tumori, Pisa, Italy

    • F Loupakis

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The authors declare no conflict of interest.

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Correspondence to H-J Lenz.

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DOI

https://doi.org/10.1038/tpj.2016.59

Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj)

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