Epidermal growth factor A61G gene polymorphism, gastroesophageal reflux disease and esophageal adenocarcinoma risk.
BACKGROUND
Single-nucleotide polymorphisms of key cancer genes, such as EGF A61G, are associated with an elevated risk of esophageal adenocarcinoma (EAC). As gastroesophageal reflux disease (GERD) is an established risk factor for EAC, we evaluated whether the association between epidermal growth factor (EGF) polymorphism and EAC development is altered by the presence of GERD.


METHODS
EGF genotyping of DNA samples was performed and GERD history was collected for 309 EAC patients and 275 matched healthy controls. Associations between genotypes and EAC risk were evaluated using adjusted logistic regression. Genotype-GERD relationships were explored using analyses stratified by GERD history and joint effects models that considered severity and duration of GERD symptoms.


RESULTS
EGF variants (A/G or G/G) were more common (P = 0.02) and GERD was more prevalent (P < 0.001) in cases than in controls. When compared with the EGF wild-type A/A genotype, the G/G variant was associated with a substantial increase in EAC risk among individuals with GERD [Odds ratio 9.7; 95% confidence interval (CI), 3.8-25.0; P < 0.001] and a slight decrease in risk for GERD-free individuals (odds ratio 0.4; 95% CI = 0.22-0.90; P = 0.02). In the joint effects models, the odds of EAC was also highest for G/G patients (when compared with A/A) who either experienced frequent GERD of more than once per week (odds ratio 21.8; 95% CI = 5.1-94.0; P < 0.001) or suffered GERD for longer than 15 years (odds ratio 22.4; 95% CI = 6.5-77.6; P < 0.001). There was a highly significant interaction between the G/G genotype and the presence of GERD (P < 0.001).


CONCLUSIONS
EGF A61G polymorphism may alter EAC susceptibility through an interaction with GERD.
Cheung
Winson Y
WY
Division of Medial Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4E6.
Zhai
Rihong
R
Kulke
Matthew H
MH
Heist
Rebecca S
RS
Asomaning
Kofi
K
Ma
Clement
C
Wang
Zhaoxi
Z
Su
Li
L
Lanuti
Michael
M
Tanabe
Kenneth K
KK
Christiani
David C
DC
Liu
Geoffrey
G
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004815:Epidermal Growth Factor / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
D004815:Epidermal Growth Factor