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

Matsusaka, S; Cao, S; Hanna, D L; Sunakawa, Y; Ueno, M; Mizunuma, N; Zhang-Wu, Xiaxia; Yang, D; Ning, Y; Stintzing, S; Sebio, A; Stremitzer, S; Yamauchi, S; Parekh, A; Okazaki, S; Berger, Martin Dave; El-Khoueiry, R; Mendez, A; Ichikawa, W; Loupakis, F; ... (2017). CXCR4 polymorphism predicts progression-free survival in metastatic colorectal cancer patients treated with first-line bevacizumab-based chemotherapy. Pharmacogenomics journal, 17(6), pp. 543-550. Nature Publishing Group 10.1038/tpj.2016.59

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Berger, Martin Dave

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1470-269X

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Nicole Corminboeuf

Date Deposited:

07 Mar 2018 18:07

Last Modified:

22 Oct 2019 19:04

Publisher DOI:

10.1038/tpj.2016.59

PubMed ID:

27503580

BORIS DOI:

10.7892/boris.111414

URI:

https://boris.unibe.ch/id/eprint/111414

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