期刊
CLINICAL CANCER RESEARCH
卷 14, 期 10, 页码 3216-3222出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-07-4932
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资金
- NCI NIH HHS [R01 CA109193-05, R01 CA092824, R03 CA110822-02, R01 CA074386-11, R01 CA090578, P50 CA090578, R01 CA074386, R03 CA110822, P20 CA090578, P50 CA090578-067601, R01 CA109193, R01 CA 092824, R01 CA092824-06] Funding Source: Medline
Purpose: The epidermal growth factor (EGF) pathway is important in esophageal adenocarcinoma (EAC) tumorigenesis. We hypothesized that the EGF A61G homozygous variant genotype (GG) is (a) both a risk and poor prognostic factor for EAC and (b) associated with higher EGF serum levels in individuals with gastroesophageal reflux disease (GERD). Experimental Design: Using unconditional logistic regression, we compared EGF A61G in 312 EAC cases and 447 GERD-free controls, adjusting for age, gender, smoking history, and healthy adult body mass index. Using the method of Kaplan and Meier, log-rank tests, and Cox proportional hazard models, we correlated EGF A61G with overall and failure-free survival in the EAC cases. Serum EGF levels and EGF genotype (GIG versus others) were correlated in 144 GERD patients using Wilcoxon rank sum tests. Results:The EGF A61G GIG genotype conferred increased EAC risk, with an adjusted odds ratio of 1.81 (95% confidence interval, 1.2-2.7), and was even higher in the subgroup of EAC patients with concurrent Barrett's esophagus (adjusted odds ratio, 2.18; 95% confidence interval, 1.3-3.7). However, EGF A61G was not associated with a more aggressive phenotype or prognosis in EAC patients. Higher serum EGF levels were found in GERD patients carrying GIG compared with A/A or A/G (P = 0.03, Wilcoxon rank sum test). Conclusion: The EGF A61G G/G genotype is associated with a near 2-fold greater risk of EAC. The GIG allele was also associated with higher EGF levels in tumor-free patients with GERD. EGF genotyping can potentially identify high-risk patients with GERD and Barrett's metaplasia who might benefit from increased surveillance.
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