Carcinogenesis Advance Access published online on June 11, 2009
Carcinogenesis, doi:10.1093/carcin/bgp126
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Epidermal Growth Factor A61G Gene Polymorphism, Gastroesophageal Reflux Disease, and Esophageal Adenocarcinoma Risk
1 British Columbia Cancer Agency, Vancouver, BC, Canada
2 Harvard School of Public Health, Boston, MA
3 Dana Farber Cancer Institute, Boston, MA
4 Massachusetts General Hospital, Boston, MA
5 Princess Margaret Hospital, Toronto, ON, Canada
6 University of Toronto, Toronto, ON, Canada
Address Correspondences and Reprints to: Geoffrey Liu, MD, MSc, FRCP(C), Staff Medical Oncologist, Princess Margaret Hospital, Assistant Professor, University of Toronto, Room 7-125, 610 University Avenue, Toronto, Ontario, M5G 2M9, Tel: 416.946.3428, Fax: 416.946.6529, Email: geoffrey.liu{at}uhn.on.ca
Background: Single nucleotide polymorphisms (SNPs) of key cancer genes, such as EGF A61G, are associated with an elevated risk of EAC. As GERD is an established risk factor for EAC, we evaluated whether the association between 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 to the EGF wild type A/A genotype, the G/G variant was associated with a substantial increase in EAC risk among individuals with GERD (OR 9.7; 95% CI, 3.8-25.0; p<0.001) and a slight decrease in risk for GERD-free individuals (OR 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 greater than once per week (OR 21.8; 95% CI, 5.1-94.0; p<0.001) or suffered GERD for longer than 15 years (OR 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.
Key Words: Epidermal growth factor • polymorphism • gastroesophageal reflux • esophageal cancer
Received February 8, 2009; revised May 13, 2009; accepted May 14, 2009.