A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome.
OBJECTIVE
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).


METHODS
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 (G/G versus others) were correlated in 144 GERD patients using Wilcoxon rank sum tests.


RESULTS
The EGF A61G G/G 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 G/G compared with A/A or A/G (P = 0.03, Wilcoxon rank sum test).


CONCLUSIONS
The EGF A61G G/G genotype is associated with a near 2-fold greater risk of EAC. The G/G 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.
Lanuti
Michael
M
Division of Thoracic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Mlanuti@partners.org
Liu
Geoffrey
G
Goodwin
Jonathan M
JM
Zhai
Rihong
R
Fuchs
Bryan C
BC
Asomaning
Kofi
K
Su
Li
L
Nishioka
Norman S
NS
Tanabe
Kenneth K
KK
Christiani
David C
DC
D000230:Adenocarcinoma / Q000097:blood* / Q000235:genetics* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000097:blood* / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000097:blood* / Q000235:genetics* / Q000401:mortality; D005260:Female; D005764:Gastroesophageal Reflux / Q000097:blood / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000097:blood / Q000235:genetics; D012307:Risk Factors; D016896:Treatment Outcome
D004815:Epidermal Growth Factor