Abstract:
BACKGROUND:The fibroblast growth factor (FGF) and FGF receptor (FGFR) axis plays a critical role in tumorigenesis, but little is known of its influence in ovarian cancer. We sought to determine the association of genetic variants in the FGF pathway with risk, therapeutic response, and survival of patients with ovarian cancer. METHODS:We matched 339 non-Hispanic white ovarian cancer cases with 349 healthy controls and genotyped them for 183 single-nucleotide polymorphisms (SNPs) from 24 FGF (fibroblast growth factor) and FGFR (fibroblast growth factor receptor) genes. Genetic associations for the main effect, gene-gene interactions, and the cumulative effect were determined. RESULTS:Multiple SNPs in the FGF-FGFR axis were associated with an increased risk of ovarian cancer. In particular, FGF1 [fibroblast growth factor 1 (acidic)] SNP rs7727832 showed the most significant association with ovarian cancer (odds ratio, 2.27; 95% CI, 1.31-3.95). Ten SNPs were associated with a reduced risk of ovarian cancer. FGF18 (fibroblast growth factor 18) SNP rs3806929, FGF7 (fibroblast growth factor 7) SNP rs9920722, FGF23 (fibroblast growth factor 23) SNP rs12812339, and FGF5 (fibroblast growth factor 5) SNP rs3733336 were significantly associated with a favorable treatment response, with a reduction of risk of nonresponse of 40% to 60%. Eleven SNPs were significantly associated with overall survival. Of these SNPs, FGF23 rs7961824 was the most significantly associated with improved prognosis (hazard ratio, 0.55; 95% CI, 0.39-0.78) and was associated with significantly longer survival durations, compared with individuals with the common genotype at this locus (58.1 months vs. 38.0 months, P = 0.005). Survival tree analysis revealed FGF2 rs167428 as the primary factor contributing to overall survival. CONCLUSIONS:Significant associations of genetic variants in the FGF pathway were associated with ovarian cancer risk, therapeutic response, and survival. The discovery of multiple SNPs in the FGF-FGFR pathway provides a molecular approach for risk assessment, monitoring therapeutic response, and prognosis.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Meng QH,Xu E,Hildebrandt MA,Liang D,Lu K,Ye Y,Wagar EA,Wu Xdoi
10.1373/clinchem.2013.211490subject
Has Abstractpub_date
2014-01-01 00:00:00pages
222-32issue
1eissn
0009-9147issn
1530-8561pii
clinchem.2013.211490journal_volume
60pub_type
杂志文章abstract::A continuous-monitoring method for measuring acid phosphatase activity with alpha-naphthyl phosphate as the substrate was critically evaluated and modified. Using partially purified prostatic acid phosphatase, we show that certain conditions for the assay must be satisfied to ensure linearity. These conditions include...
journal_title:Clinical chemistry
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journal_title:Clinical chemistry
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abstract:BACKGROUND:In the workup of patients with suspected hereditary nonpolyposis colorectal cancer (HNPCC), detection of loss of heterozygosity (LOH) could help pinpoint the mismatch-repair (MMR) gene carrying the germline mutation, but analysis of microsatellite markers has proved unreliable for this purpose. We developed ...
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journal_title:Clinical chemistry
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更新日期:1977-07-01 00:00:00
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journal_title:Clinical chemistry
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abstract::Autocorrelation of clinical chemistry quality-control (Q/C) measurements causes one of the basic assumptions underlying the use of Levey-Jennings control charts to be violated and performance to be degraded. This is the requirement that the observations be statistically independent. We present a proposal for a new app...
journal_title:Clinical chemistry
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journal_title:Clinical chemistry
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更新日期:1998-03-01 00:00:00
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journal_title:Clinical chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1994-07-01 00:00:00
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更新日期:1995-09-01 00:00:00
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journal_title:Clinical chemistry
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更新日期:1983-02-01 00:00:00
abstract::We compare measurement of total fast hemoglobin (HbA1) by "high-performance" liquid chromatography and by electrophoresis on agar gel. Blood samples were obtained from a diverse population (n = 222): offspring of two diabetic parents, diabetic patients with and without retinopathy, diabetic and non-diabetic pregnant w...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1981-03-01 00:00:00
abstract::We describe a mechanized method for centrifugal analyzer determination of sorbitol dehydrogenase in serum, based on conversion of D-fructose to sorbitol with simultaneous oxidation of NADH, in triethanolamine buffer at pH 7.4 and 30 degrees C. The standard curve for this assay is linear to 200 U of activity per liter ...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1979-12-01 00:00:00
abstract::We directly compared the reliability of a single-isotope enzymatic derivative technique for measurement of plasma catecholamines with that of the well-established double-isotope method. A significant (p less than 0.001) correlation was observed between measurements (n = 52) in the two assays, both for norepinephrine (...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1978-04-01 00:00:00
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journal_title:Clinical chemistry
pub_type: 临床试验,杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::Assays with different specificity are used for cyclosporin monitoring in clinical transplantation. A recent survey of 35 centers showed that 86% used immunoassays for cyclosporin A (CsA). In consensus documents the following performance criteria were recommended: (a) imprecision < or = 10% at 50 microg/L and < or = 5%...
journal_title:Clinical chemistry
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doi:
更新日期:1998-10-01 00:00:00
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doi:10.1373/clinchem.2016.261495
更新日期:2017-01-01 00:00:00
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journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1988-11-01 00:00:00
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journal_title:Clinical chemistry
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doi:
更新日期:1987-09-01 00:00:00
abstract::Major depression is one of the most common clinical problems seen by primary-care physicians. The prevalence is 5% to 10% in primary-care outpatients and 15% in medically ill inpatients. Despite this high prevalence rate, depression is frequently not accurately diagnosed. Evidence suggests that misdiagnosis often occu...
journal_title:Clinical chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1988-05-01 00:00:00
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doi:
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND:A substantial proportion of the variability in the absorption and clearance of cyclosporin A (CsA) after oral administration has been attributed to variability in liver cytochrome P-450 3A4 (CYP3A4) activity and intestinal P-glycoprotein (P-gp) concentration. A polymorphism in the CYP3A4 promoter region, ter...
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更新日期:2001-06-01 00:00:00
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journal_title:Clinical chemistry
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doi:
更新日期:1978-11-01 00:00:00
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更新日期:1976-11-01 00:00:00
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journal_title:Clinical chemistry
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doi:
更新日期:1983-07-01 00:00:00
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journal_title:Clinical chemistry
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journal_title:Clinical chemistry
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更新日期:1975-09-01 00:00:00
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journal_title:Clinical chemistry
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doi:
更新日期:1988-04-01 00:00:00
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journal_title:Clinical chemistry
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doi:
更新日期:1978-02-01 00:00:00
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