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 allele<or=16 repeats) genotypes were statistically higher among the cases than in the controls (OR: 1.94 and 3.04, 95% CI: 1.16-3.23 and 1.53-6.04, P-value: 0.01 and 0.001, respectively). When the length of EGFR-CA repeat was analyzed by the sum of the number of repeats in two alleles, the frequency of the shorter repeats (sum<or=36) was 79.6% versus 63.4%, respectively, and the frequency of the longer repeats (sum>36) 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.
Zhang
Weiping
W
Department of Pharmacology, University of Pittsburgh Cancer Institute, SPORE in Lung Cancer, University of Pittsburgh, Pittsburgh, Pennsylvania 15213-1863, USA.
Weissfeld
Joel L
JL
Romkes
Marjorie
M
Land
Stephanie R
SR
Grandis
Jennifer R
JR
Siegfried
Jill M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D018900:Dinucleotide Repeats; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D044465:White People
D004273:DNA, Neoplasm; D066246:ErbB Receptors