Literature DB >> 27503580

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

S Matsusaka1, S Cao1, D L Hanna1, Y Sunakawa1, M Ueno2, N Mizunuma3, W Zhang1, D Yang1, Y Ning1, S Stintzing1, A Sebio1, S Stremitzer1, S Yamauchi1, A Parekh1, S Okazaki1, M D Berger1, R El-Khoueiry1, A Mendez1, W Ichikawa4, F Loupakis5, H-J Lenz1.   

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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Year:  2016        PMID: 27503580      PMCID: PMC7496215          DOI: 10.1038/tpj.2016.59

Source DB:  PubMed          Journal:  Pharmacogenomics J        ISSN: 1470-269X            Impact factor:   3.550


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