A Pilot Study On Relationship Between EGFR Genetic Polymorphism And Radiosensitivity Of Esophageal Cancer

Backgrouds and aims:Esophageal cancer is one of the most common malignant tumors inchina, with poor prognosis. Clinical studies showed that the effect ofradiotherapy varied even with the same general condition, age, clinical stageand pathological type. This might be attributed to individual tumorradiosensitivity.The epidermal growth factor receptor belongs to the ErbB family oftyrosine kinase receptors, which include EGFR(ErbB-1),HER-2/neu(ErbB-2), HER-3(ErbB-3)，and HER-4(ErbB-4), all of which areinvolved in modulating pathways of tumor growth or proliferation. Apolymorphic variant EGFR arising from a single nucleotide change（Gâ†'A）leading to an arginine (Arg)â†'lysine(Lys) substitution in codon 497(HER-1R497K) in the extracellular domain within subdomain IV of the EGFRgene as been identified. An in vitro study has shown that the variant HER-1497K has attenuated functions in ligand binding, growth stimulation,tyrosine kinase activation, and induction of proto-oncogenes myc, fos, andjun compared with the‘‘wild-type’’HER-1 497R. At present, it is still lack of convenient and accurate predictive methodsand parameters for radiosensitivity of esophageal cancers. This study aimedto use Polymerase Chain Reaction Restriction Fragment Length Polymorphism technique (PCR-RFLP)to detect the genotypes of EGFR R497K in peripheral blood leukocytes frompatients with esophageal cancers, and to explore the relationship between thegenetic polymorphism of EGFR and radiosensitivity of esophageal cancersin the population from the North Sichuan of China. It is hoped to provide atheoretical basis for the optimization of individual treatment plan.Materials and methods:1. The subjects of this study were 69 patients with untreated esophagealcancers, confirmed by pathology. 2ml of peripheral blood was drawn fromeach patients before treatment, and whole genomic DNA was extracted fromblood samples using a DNA kit. The genotypes of HER-1 R497K weredetected by PCR-RFLP.2. All the patients underwent three-dimensional conformal radiotherapyalone. Tumor regression was assessed by CT and Barium meal examinationat the end of radiotherapy and about two months after radiotherapy,respectively.3. The statistics was performed using SPSS version 17.0. Therelationship between HER-1 R497K genotypes and radiosensitivity of esophageal cancers and clinicopathological characteristics was investigated.Results：1. 56 cases (81.2%) were assessed to be effective after radiotherapy,while 13 cases (18.8%) ineffective. Among these 69 patients, 18 (26.1%), 35(50.7%) and 16 (23.2%) had the A/A (Lys/Lys), A/G (Lys/Arg), G/G(Arg/Arg) genotypes, respectively.2. HER-1 R497K genotypes were found to be associated with theresponse to radiotherapy. The effective rates for patients carrying A/A, A/Gand G/G genotypes were 100% (18/18), 74.3% (26/35) and 75% (12/16),respectively. There is significant difference between A/A and A/G carriers(P=0.048) and also between A/A and G/G carriers (P=0.039). There is nosignificant difference between A/G and G/G carriers (P=0.957).3. There is no significant correlation between R497K genotypes andclinical features such as gender, age, clinical stages and degrees ofdifferentiation.4. Compared to middle and lower thoracic ,Upper segment thoracicpatients is better response to irradiation therapy. Lesions length <5cm inpatients with radiotherapy effect is better than the length≥5cm.Thelocation and length of lesions was associate with the effect of radiotherapy(P<0.05). Conclusions:1. HER-1 R497K genotypes were found to be associated with theresponse to radiotherapy. The patients carrying A/A type were more sensitiveto radiotherapy compared with patients carrying A/G and G/G types. Therewas no significant difference between A/G and G/G carriers.2. There was no significant difference between HER-1 R497Kgenotypes and clinicopathological characteristics.3. EGFR polymorphism might serve as a potential radiosensitivityindicator for esophageal cancer radiotherapy. It might provide a potentialtheoretical basis for selecting appropriate patients to different treatments andoptimizing the individual treatment plans.