3433

Epidermal growth factor receptor (EGFR), a trans-membrane receptor, plays a critical role in signal transduction pathway for cell proliferation, differentiation and survival. Overexpression of EGFR has been reported in various solid tumors, including bladder cancer. The specific aim of this study is to investigate the association between genetic polymorphisms of EGFR and the risk of urothelial carcinoma (UC). A total of 325 pathologically confirmed UC cases and 328 controls were serially recruited from the Chi Mei Medical Center and the Chia Yi Christian Hospital. Cancer-free controls were matched to the cases by age and gender. All study subjects were interviewed by well-trained interviewers with a standardized structured questionnaire to collect information about demographic variables and other risk factors. Genetic polymorphisms of EGFR were determined by polymerase chain reaction- restriction fragment length polymorphism assay. Odds ratios (ORs) and 95% confidence interval (CI), obtained from an unconditional multiple logistic regression, were used to estimate the strength of the association between genetic polymorphisms of EGFR and the risk of UC. Our results found that ever smokers had two-fold risk for development of UC after adjustment for age, gender and alcohol intake. Study subjects with the EGFR 497RR genotype had a 1.7-fold risk of UC compared to other genotypes.Among those with the EGFR 2073TT genotype, we observed a statistically significant increased UC risk (OR=1.7, 95% CI: 1.1-2.5). Study subjects carrying both two risk genotypes of EGFR have a significant increased UC risk (OR=1.9, 95% CI: 1.2-3.0). Compared with study subjects carrying the EGFR 497K-2073A haplotype, we observed a significant increased UC risk (OR=1.4, 95% CI: 1.1-1.7) among those with the 497R-2073T haplotype. The joint effect between genetic polymorphisms of EGFR and cigarette smoking was further examined. Ever smokers with the EGFR 497RR genotype and the EGFR 2073TT genotype have significantly increased UC risks, showing OR and 95% CI of 3.3 and 1.8-6.1, and 3.2 and 1.7-6.1, respectively. Our results suggest that EGFR R497K and A2073T polymorphisms were significantly associated with the risk of UC. It also implied that genetic polymorphisms of EGFR may be a potential marker for the development of UC.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA