In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. 600-600
Abstract:
600 Background: The molecular effects of obesity are mediated by alterations in the levels of adipokines, which are produced mainly by adipose tissue. Adipokines have multiple effects, including insulin sensitivity, cell proliferation, inflammation, and angiogenesis. We previously reported that single-nucleotide polymorphisms (SNPs) in obesity-related genes were associated with the recurrence probability of CRC treated with 5-FU based adjuvant chemotherapy. This study aimed to evaluate whether SNPs in adipokine-related genes may predict clinical outcomes in bevacizumab treated mCRC pts. Methods: Genomic DNA was obtained from mCRC pts receiving bevacizumab plus FOLFIRI as first-line treatment and analyzed by using PCR-based direct sequencing. Eleven functional SNPs in 7 genes ( LEP, LEPR, ADIPOQ, ADIPOR1, RETN, TNFa and NAMPT) were tested in 291 pts in FIRE3 trial bevacizumab cohort (NCT00433927). Main characteristics were the following: male/female = 193/98; median age = 65; High BMI pts (BMI ≥ 25 Kg/m 2 )/low BMI pts (BMI 〈 25 Kg/m 2 ) = 162/129; median PFS = 10.1 months; median OS = 24.2 months, median follow-up time = 40.8 months. Results: LEPR rs1137100 G/G variants (n = 24) showed worse PFS than any A variants (n = 246) in univariate (10.4 months (M) vs. 9.2 M, HR = 1.75, 95%CI = 1.12-2.74, P = 0.011) and multivariate analyses (HR = 1.75, 95%CI = 1.11-2.74, P = 0.016). NAMPT rs61330082 T/T (n = 24) showed worse PFS than any C variants (n = 243) in multivariate analysis (HR = 1.65, 95% = 1.02-2.67, P = 0.042). RETN rs1862513 C/C (n = 23) showed worse OS than any G variants (n = 246) in univariate analysis (14.1 m vs. 25.1 M, HR = 1.65, 95%CI = 1.04-2.60, P = 0.029). In subgroup analyses of high BMI pts, the prognostic effect of LEPR rs1137100 G/G and RETN rs1862513 C/C was confirmed and no association was observed among low BMI pts. Conclusions: Our study showed for the first time that genetic variations in adipokine-related genes are associated with prognosis of mCRC pts treated with bevacizumab based chemotherapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.4_suppl.600
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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