The Association Between Single Nucleotide Polymorphisms Of Epidermal Growth Factor Receptor And Radiochemotherapy Response In Cervical Cancer

Objective: Epidermal growth factor receptor(EGFR) plays a critical rolein the signal transduction pathway for cell proliferation, differerntiation,migration, motility, resistance to apoptosis and enhance cell survival. Manyinvestigations show EGFR overexpression is realated to low differentiation,positive lymphnode and poor prognosis in cervical carcinoma. But, theseworks were only at protein level of EGFR. This study was designed toinvestigate the association of EGFR R497K (rs11543848) and-216G/T(rs712829) single nucleotide polymorphisms with radiochemotherapyresponse in cervical cancer.Methods: From January2010to May2011one hundred and ninety-sixpatients with cervical cancer were recruited for this study. All patients weretreated with radiotherapy, among whom41received single radiotherapy, and155received combined chemotherapy. Age, clinical treatment and evaluationof curative effect were collected from records. According to ResponseEvaluation Criteria in Solid Tumors(RECIST),127cases were completeremission(CR) and69cases were partial remission(PR). Some patients'survival information was got by telephone and letter, and the others tookperiodic review in clinic. Until February2012,147patients were disease-freesurvival,46patients appeared recurrence/metastasis and3patients were lost.Genomic DNA was extracted by using proteinase K digestion followed by asalting out procedure. Genotype frequencies of R497K and-216G/T wereanalyzed by polymerase chain reaction-ligation detection reaction (PCR-LDR).Statistical analysis was performed using SPSS13.0software package. P<0.05was considered significant for all statistical analyses. Genotypefrequencies were compared in patients group using Chi-square test and logisticregession.Results:1. For the R497K polymorphsim, the frequencies of G/G, G/A and A/Agenotypes between CR group(16.53%,55.12%and28.35%, respectively)and PR group(28.99%,53.62%and17.39%, respectively) showed nosignificant difference (χ~2=5.522, P=0.063). Compared with the G/Ggenotype, G/A genotype had no relationship with sensitivity toradiochemotherapy (adjusted OR=0.436,95%CI=0.187~1.017). the A/Agenotype significantly increased sensitivity to radiochemotherapytreatment (adjusted OR=0.244,95%CI=0.087~0.680).2. In follow-up time, the difference of distribution of G/G, G/A and A/Agenotypes between non-recurrence/metastasis group (18.37%,53.74%and28.89%, respectively) and recurrence/metastasis group(28.26%,58.70%and13.04%, respectively) was not significant (χ~2=4.983, P=0.083).Compared with the G/G genotype, G/A genotype had no relationship withthe risk of recurrence/metastasis(adjusted OR=0.696,95%CI=0.292~1.657),the A/A genotype could decrease the risk of recurrence/metastasis (adjustedOR=0.248,95%CI=0.078~0.786, P＜0.05).3. For the-216G/T polymorphsim, the frequencies of the G/G, G/T+T/Tgenotypes between CR patients (91.34%,8.66%, respectively) and PRpatients (82.61%,17.39%, respectively) showed no significant difference(χ~2=3.290,P=0.070). Compared with the G/G genotype, the carriers of 'T'allele were not significantly modified sensitivity to radiochemotherapy(adjusted OR=2.412,95%CI=0.856~6.979).4. The distribution of G/G, G/T+T/T genotypes betweennon-recurrence/metastasis group (88.44%,11.56%, respectively) andrecurrence/metastasis group (89.13%,10.87%, respectively) was notstatistically different (χ~2=0.017, P=0.897). Compared with the G/Ggenotype, the carriers of 'T' allele were not significantly modified risk of recurrence/metastasis(adjusted OR=1.027,95%CI=0.324~3.253).5. Clinical stage, tumor size, radiotherapy technology and radiotherapy dosehad relationship with treatment response (P＜0.05), but age, pathologicaltype, neoplasms form and treatment mode had no statistically significantbased on univariate analysis(P＞0.05). Furthermore, clinical stage wasassociated with treatment response based on multivariate analysis (P＜0.05).6. Age had relationship with the risk of recurrence/metastasis (P＜0.05), butclinical stage, pathological type, neoplasms form, tumor size, treatmentmode, radiotherapy technology and radiotherapy dose had no significantdifference based on univariate analysis(P＞0.05). The age of patients wasonly associated with the risk of recurrence/metastasis based on multivariateanalysis.(P＜0.05).Conclusions:1. In our study, the R497K polymorphisms have a relationship with treatmentresponse and the risk of recurrence/metastasis for cervical cancer.Compared with G/G genotype, the A/A genotype carriers have asignificantly better treatment response and lower risk ofrecurrence/metastasis in follow-up time. R497K SNP might be a geneticmarker for prediction radiochemotherapy response and the risk ofrecurrence/metastasis of patients with cervical cancer.2. EGFR-216G/T polymorphisms located in the promoter region of EGFRgene are not associated with treatment response, neither with the risk ofrecurrence or metastasis of patients with advanced cervical cancer.3. Clinical stage plays a critical role in radiochemotherapy response ofcervical cancer. Age is an important factor that affect the risk ofrecurrence/metastasis.