Carcinogenesis Advance Access originally published online on June 11, 2009
Carcinogenesis 2009 30(8):1363-1367; doi:10.1093/carcin/bgp126
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Epidermal growth factor A61G gene polymorphism, gastroesophageal reflux disease and esophageal adenocarcinoma risk
1 Division of Medial Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4E6
2 Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA
3 Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
4 Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
5 Division of Medical Oncology, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
6 Department of Medicine, University of Toronto, Toronto, Ontario, Canada M5G 2M9
* To whom correspondence should be addressed. Tel: +1 416 946 3428; Fax: +1 416 946 6529; Email: geoffrey.liu{at}uhn.on.ca
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.
Abbreviations: AOR, adjusted odds ratio; BE, Barrett's esophagus; BMI, body mass index; CI, confidence intervals; EAC, esophageal adenocarcinoma; EGF, epidermal growth factor; GERD, gastroesophageal reflux disease
Received February 8, 2009; revised May 13, 2009; accepted May 14, 2009.