High risk for lung and bladder cancers in the Arabian Gulf population associated with EGFR genetic variants regulating expression

The Epidermal growth factor receptor (EGFR) expression is controlled by a polymorphic CA simple sequence repeat 1 [CA-SSR1] in intron one, and two single nucleotide polymorphisms (SNPs) in the promoter region (-216 G/T,-191C/A). We investigated the EGFR cell surface expression level and analyzed these genomic markers in six types of adenocarcinoma in Arabian patients. The highest expression of EGFR was observed in lung (93%) and bladder (95%) cancers. The CA-SSR1 long allele (OR=1.641, 95% CI 1.01-2.66, p=0.044) and the SNP-191C/A A allele (OR=3.87, 95% CI 1.51-9.87, p=0.004) were significantly associated with lung adenocarcinoma (LA). Haplotype analysis revealed three haplotypes within EGFR gene were significantly associated with lung and bladder cancer risk. However, after Bonferroni correction only haplotype SSR1L/-216G/-191A remained significantly associated with increased lung cancer risk (OR=4.652, 95% CI 1.47-14.71, p=0.012). This is the first observation of a significant association between genetic markers influencing EGFR expression level and the risk of developing lung cancers in Arabs. Furthermore, the molecular event that favors the selection of the long SSR1 allele in Arab lung cancer patients seems to be different from the somatic mutation that favors the selection of the short allele in the East Asian lung cancer patients.