Abstract
Polymorphisms in DNA repair pathways may play a relevant role in lung cancer survival in never-smokers. Furthermore, they could be implicated in the response to chemotherapy and toxicity of platinum agents. The aim of this study was to evaluate the influence of various genetic polymorphisms in the BER and NER DNA repair pathways on survival and toxicity in never-smoker LC patients. The study included never-smokers LC cases diagnosed from 2011 through 2019, belonging to the Lung Cancer Research In Never Smokers study. A total of 356 never-smokers cases participated (79% women; 83% adenocarcinoma and 65% stage IV). Survival at 3 and 5 years from diagnosis was not associated with genetic polymorphisms, except in the subgroup of patients who received radiotherapy or chemo-radiotherapy, and presented with ERCC1 rs3212986 polymorphism. There was greater toxicity in those presenting OGG1 rs1052133 (CG) and ERCC1 rs11615 polymorphisms among patients treated with radiotherapy or chemo-radiotherapy, respectively. In general, polymorphisms in the BER and NER pathways do not seem to play a relevant role in survival and response to treatment among never-smoker LC patients.
Highlights
Lung cancer (LC) is an important public health problem, ranking as the leading cause of cancer-related death and causing approximately 1.4 million deaths annually w orldwide[1]
There are studies which show that polymorphisms in genes involved in DNA repair may influence the non-small cell lung cancer prognosis[15]
Mean age at diagnosis was similar in both sexes, the predominant histologic type was adenocarcinoma (83%), and the most frequent stage at diagnosis was IV (65%). 25% of all patients received chemotherapy, 11% received radiotherapy, and 28% received chemo-radiotherapy
Summary
Lung cancer (LC) is an important public health problem, ranking as the leading cause of cancer-related death and causing approximately 1.4 million deaths annually w orldwide[1]. Little is known about how genetic susceptibility may influence lung cancer survival. This ignorance is greater when it comes to never-smokers, and is greater still when genetic susceptibility is combined with the treatments received. Some genetic polymorphisms have been linked to the response to certain chemotherapy treatments, Research Group, Health Research Institute of Santiago de Compostela (Instituto Investigación Sanitaria de Santiago de Compostela/IDIS), Santiago de Compostela, Spain. There are two DNA repair mechanisms, known as base excision repair (BER) and nucleotide excision repair (NER), respectively. There are studies which show that polymorphisms in genes involved in DNA repair (like ERCC1: excision repair 1 gene) may influence the non-small cell lung cancer prognosis[15]
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