Association of the EGFR intron 1 CA repeat length with lung cancer risk

Epidermal growth factor receptor (EGFR) plays an important role in the development and progression of lung cancer. A previous report noted that an increased number of polymorphic CA repeats in the first intron of the EGFR gene results in decreased transcriptional activity. To estimate the association of the length of polymorphic CA repeats in intron 1 of the EGFR gene with lung cancer, a case-control study of 176 lung cancer patients and 161 controls was conducted in Caucasians. This case-control study is based on two existing prospective cohorts: the Early Detection Research Network (EDRN) and the Lung Cancer Specialized Program of Research Excellence (SPORE) at the University of Pittsburgh. The frequencies of the SL (one allele>16 repeats), and SS (both allele36) was 20.5% versus 36.7%, for lung cancer cases versus controls. The lower sum of EGFR-CA repeats associated with the risk of lung cancer; the estimated odds ratio was 2.25 with 95% confidence interval: 1.38-3.66 (P=0.001). Associations involving EGFR-CA repeat genotype and EGFR-CA repeat sum remained significant when adjusted for age, gender, and tobacco exposure. Our study, which is preliminary, demonstrates for the first time that shorter EGFR-CA repeats associate with lung cancer risk. The number of EGFR-CA repeats identifies a possible susceptible population to lung cancer.