title: The epidermal growth factor receptor intron1 (CA) n microsatellite polymorphism is a potential predictor of treatment outcome in patients with advanced lung cancer treated with Gefitinib.
abstract: The goal of our study was to assess the association between R497K and intron1 (CA) n repeat genetic polymorphisms of the EGF (epidermal growth factor) receptor and the clinical outcome of patients with advanced non-small cell lung cancer treated with EGF receptor tyrosine kinase inhibitor. We determined the genotypes for R497K and intron1 (CA) n repeat genetic polymorphisms of 70 Chinese patients with advanced non-small cell lung cancer. Genetic polymorphisms were correlated with the clinical outcome of treatment with EGF receptor tyrosine kinase inhibitor. In a subgroup of patients whose tumor tissues were available for mutation analysis and IHC (immunohistochemistry) assay, the associations between the EGF receptor mutations, the EGF receptor protein expression levels and EGF receptor polymorphisms were analyzed. The results indicated that patients with a lower number of EGF receptor CA repeats (any allele < or =16 CA) were more likely to have higher EGF receptor protein expression levels, better response, and longer survival time than were patients with a higher number of CA repeats (both alleles >16 CA) after therapy targeted at the EGF receptor (P=0.021; P=0.014; P=0.0392, respectively). In contrast, the R497K polymorphism had no relationship with EGF receptor protein expression levels or the clinical outcome of the patients treated with EGF receptor tyrosine kinase inhibitor (P=0.49; P=0.452, respectively), and there were no associations between the two polymorphisms and somatic mutations (P=0.916; P=0.562, respectively). Overall, our data suggest that the intron1 (CA) n polymorphism of the EGF receptor gene may be associated with the sensitivity to and the prognosis of non-small cell lung cancer after EGF receptor targeted inhibitor treatment.
authors.affiliation: Lung Cancer Research Institute and Cancer Center, Guangdong Provincial People's Hospital, Guangzhou, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Nie
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Guo-Chun
authors.initials: GC
authors.lastname: Zhang
authors.forename: She-Juan
authors.initials: SJ
authors.lastname: An
authors.forename: Jia-Yin
authors.initials: JY
authors.lastname: Lin
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Guo
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Gan
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Tony S
authors.initials: TS
authors.lastname: Mok
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib