EGF+61 A>G polymorphism does not predict response to first‐generation EGFR tyrosine kinase inhibitors in lung cancer patients
Epidermal growth factor (EGF) and its receptor (EGFR) play a paramount role in lung carcinogenesis. The polymorphism in the EGF promoter region EGF+61A>G (rs4444903) has been associated with cancer susceptibility, but its role in lung cancer patients treated with tyrosine kinase inhibitors (TKIs)...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-10-01
|
| Series: | Thoracic Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1759-7714.13628 |
| _version_ | 1828397048195448832 |
|---|---|
| author | Leticia F. Leal Ana C. Laus Rodrigo Cavagna Flavia E. dePaula Marco A. deOliveira Dayana M. Ribeiro Fernanda M. Hassan José E. Miziara Eduardo C. Albino daSilva Vinicius D. daSilva Pedro De Marchi Rui M. Reis |
| author_facet | Leticia F. Leal Ana C. Laus Rodrigo Cavagna Flavia E. dePaula Marco A. deOliveira Dayana M. Ribeiro Fernanda M. Hassan José E. Miziara Eduardo C. Albino daSilva Vinicius D. daSilva Pedro De Marchi Rui M. Reis |
| author_sort | Leticia F. Leal |
| collection | DOAJ |
| description | Epidermal growth factor (EGF) and its receptor (EGFR) play a paramount role in lung carcinogenesis. The polymorphism in the EGF promoter region EGF+61A>G (rs4444903) has been associated with cancer susceptibility, but its role in lung cancer patients treated with tyrosine kinase inhibitors (TKIs) remains unknown. Here, we aimed to evaluate the predictive and prognostic role of EGF+61A>G SNP in lung cancer from Brazilian EGFR‐mutated TKI‐treated patients. Herein, patients carrying EGFR‐sensitizing mutations submitted to TKI treatment (gefitinib/erlotinib) were analyzed (n = 111) for EGF+61A>G genotype by TaqMan genotyping assay. TKI treatment was classified as partial response (PR), stable disease (SD), and disease progression (DP), according to RECIST1.1. Association analysis was assessed by chi‐square and Fisher's test (univariate) and multinomial model (multivariate) and survival analysis by Kaplan‐Meier method and log‐rank test. The EGF+61A>G genotype frequencies observed were: AA = 31.5% (n = 35), AG = 49.6% (n = 55) and GG = 18.9% (n = 21). The allelic frequencies were 56.3% for A, and 43.7% for G and the population was in Hardy‐Weinberg equilibrium (P = 0.94). EGF+61A>G codominant model (AA vs. AG vs. GG) was associated with a response to TKIs (P = 0.046), as well as a recessive model (AA vs. AG + GG; P = 0.023). The multinomial regression showed an association between the codominant model (AG) and recessive model (AG + GG) with SD compared with DP (P = 0.01;OR = 0.08; 95% CI = 0.01–0.60 and P = 0.02;OR = 0.12; 95% CI = 0.20–0.72, respectively). No association between genotypes and progression‐free or overall survival was observed. In conclusion, the EGF+61 polymorphism (AG and AG + GG) was independently associated with stable disease in lung cancer patients although it was not associated with the overall response rate to first‐generation TKIs or patient outcome. |
| first_indexed | 2024-12-10T08:39:55Z |
| format | Article |
| id | doaj.art-fe78c0c604b747208a6a339545910160 |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-12-10T08:39:55Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-fe78c0c604b747208a6a3395459101602022-12-22T01:55:52ZengWileyThoracic Cancer1759-77061759-77142020-10-0111102987299210.1111/1759-7714.13628EGF+61 A>G polymorphism does not predict response to first‐generation EGFR tyrosine kinase inhibitors in lung cancer patientsLeticia F. Leal0Ana C. Laus1Rodrigo Cavagna2Flavia E. dePaula3Marco A. deOliveira4Dayana M. Ribeiro5Fernanda M. Hassan6José E. Miziara7Eduardo C. Albino daSilva8Vinicius D. daSilva9Pedro De Marchi10Rui M. Reis11Molecular Oncology Research Center Barretos Cancer Hospital Barretos BrazilMolecular Oncology Research Center Barretos Cancer Hospital Barretos BrazilMolecular Oncology Research Center Barretos Cancer Hospital Barretos BrazilMolecular Diagnosis Center Barretos Cancer Hospital Barretos BrazilDepartment of Epidemiology and Biostatistics Barretos Cancer Hospital Barretos BrazilDepartment of Clinical Oncology Barretos Cancer Hospital Barretos BrazilDepartment of Clinical Oncology Barretos Cancer Hospital Barretos BrazilDepartment of Surgery Barretos Cancer Hospital Barretos BrazilDepartment of Pathology Barretos Cancer Hospital Barretos BrazilDepartment of Pathology Barretos Cancer Hospital Barretos BrazilDepartment of Clinical Oncology Barretos Cancer Hospital Barretos BrazilMolecular Oncology Research Center Barretos Cancer Hospital Barretos BrazilEpidermal growth factor (EGF) and its receptor (EGFR) play a paramount role in lung carcinogenesis. The polymorphism in the EGF promoter region EGF+61A>G (rs4444903) has been associated with cancer susceptibility, but its role in lung cancer patients treated with tyrosine kinase inhibitors (TKIs) remains unknown. Here, we aimed to evaluate the predictive and prognostic role of EGF+61A>G SNP in lung cancer from Brazilian EGFR‐mutated TKI‐treated patients. Herein, patients carrying EGFR‐sensitizing mutations submitted to TKI treatment (gefitinib/erlotinib) were analyzed (n = 111) for EGF+61A>G genotype by TaqMan genotyping assay. TKI treatment was classified as partial response (PR), stable disease (SD), and disease progression (DP), according to RECIST1.1. Association analysis was assessed by chi‐square and Fisher's test (univariate) and multinomial model (multivariate) and survival analysis by Kaplan‐Meier method and log‐rank test. The EGF+61A>G genotype frequencies observed were: AA = 31.5% (n = 35), AG = 49.6% (n = 55) and GG = 18.9% (n = 21). The allelic frequencies were 56.3% for A, and 43.7% for G and the population was in Hardy‐Weinberg equilibrium (P = 0.94). EGF+61A>G codominant model (AA vs. AG vs. GG) was associated with a response to TKIs (P = 0.046), as well as a recessive model (AA vs. AG + GG; P = 0.023). The multinomial regression showed an association between the codominant model (AG) and recessive model (AG + GG) with SD compared with DP (P = 0.01;OR = 0.08; 95% CI = 0.01–0.60 and P = 0.02;OR = 0.12; 95% CI = 0.20–0.72, respectively). No association between genotypes and progression‐free or overall survival was observed. In conclusion, the EGF+61 polymorphism (AG and AG + GG) was independently associated with stable disease in lung cancer patients although it was not associated with the overall response rate to first‐generation TKIs or patient outcome.https://doi.org/10.1111/1759-7714.13628EGF+61 A>G polymorphismEGFRfirst‐generation TKI SNPlung cancerTKI |
| spellingShingle | Leticia F. Leal Ana C. Laus Rodrigo Cavagna Flavia E. dePaula Marco A. deOliveira Dayana M. Ribeiro Fernanda M. Hassan José E. Miziara Eduardo C. Albino daSilva Vinicius D. daSilva Pedro De Marchi Rui M. Reis EGF+61 A>G polymorphism does not predict response to first‐generation EGFR tyrosine kinase inhibitors in lung cancer patients Thoracic Cancer EGF+61 A>G polymorphism EGFR first‐generation TKI SNP lung cancer TKI |
| title | EGF+61 A>G polymorphism does not predict response to first‐generation EGFR tyrosine kinase inhibitors in lung cancer patients |
| title_full | EGF+61 A>G polymorphism does not predict response to first‐generation EGFR tyrosine kinase inhibitors in lung cancer patients |
| title_fullStr | EGF+61 A>G polymorphism does not predict response to first‐generation EGFR tyrosine kinase inhibitors in lung cancer patients |
| title_full_unstemmed | EGF+61 A>G polymorphism does not predict response to first‐generation EGFR tyrosine kinase inhibitors in lung cancer patients |
| title_short | EGF+61 A>G polymorphism does not predict response to first‐generation EGFR tyrosine kinase inhibitors in lung cancer patients |
| title_sort | egf 61 a g polymorphism does not predict response to first generation egfr tyrosine kinase inhibitors in lung cancer patients |
| topic | EGF+61 A>G polymorphism EGFR first‐generation TKI SNP lung cancer TKI |
| url | https://doi.org/10.1111/1759-7714.13628 |
| work_keys_str_mv | AT leticiafleal egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT anaclaus egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT rodrigocavagna egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT flaviaedepaula egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT marcoadeoliveira egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT dayanamribeiro egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT fernandamhassan egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT joseemiziara egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT eduardocalbinodasilva egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT viniciusddasilva egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT pedrodemarchi egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients AT ruimreis egf61agpolymorphismdoesnotpredictresponsetofirstgenerationegfrtyrosinekinaseinhibitorsinlungcancerpatients |