Lung cancer is called primary bronchogenic carcinoma and is a malignant tumor derived from the trachea, bronchial mucosa or glands, and is currently the most common malignant tumor in the world. According to statistics, in 2015, the incidence of lung cancer in Chinese men and women was 50.9 per 100,000 person-years and 22.4 per 100,000 person-years, respectively, which is the most important cause of death in cancer patients . At present, surgery is still the treatment of choice for early stage lung cancer, most lung cancer patients have been diagnosed at an advanced stage, lost the best treatment opportunity, and its 5-year survival rate is only 19.7% [1, 3]. Most studies suggested that the occurrence of Lung cancer is related to environmental, such as smoking, occupational exposure, and air pollution [4, 5]. At the same, genetic factors play an important role in the development of lung cancer, including EGFR, CHRNA5, CLPTM1L, TP63, and so on.
GTF2H1 (general transcription factor IIH subunit 1, GTF2H1, p62) protein plays an important role in the nucleotide excision repair (NER) pathway, participates in the early damage recognition of XPC-HR23B protein, and recruits endonuclease XPG to the injury site to complete the enzymatic cleavage process[10-12]. In addition, the GTF2H1 protein is involved in transcription and regulates transcriptional activation of multiple genes. One research found that the variants of rs3802967 and rs4150606 on GTF2H1 gene increased the risk of lung cancer, and rs4150667 on GTF2H1 gene variant reduced the risk of lung cancer . So, the genetic polymorphism of GTF2H1 gene may be involved in the pathogenesis of lung cancer.
RAD54L2, also known as ARIP4 (Androgen Receptor-Interacting Protein 4), is a protein-coding gene, which belongs to the RAD54 subfamily of SNF2-type chromatin remodeling factor superfamily , and has the double-stranded DNA-dependent ATPase activity. In fact, Rad54 interacts with Rad51 and thereby enhances its ability to form cruciform and D-loops. RAD51 catalyzes DNA repair by homologous recombination (HR) to ensure the stability of cell genome. In a study of the effects of RAD51 G135C polymorphism on NSCLC patients treated with platinum-paclitaxel / gemcitabine Wrst line chemotherapy, we found that the G135C allele was associated with a higher survival time and had a better prognosis . However, the effect of RAD54L2 gene on the occurrence and development of lung cancer is unknown.
The occurrence and development of tumors are closely related to genetic susceptibility and mutation. The genotypes have racial differences. Gene mutation is related to regional environmental factors, perennial hypobaric hypoxia and strong ultraviolet radiation in high altitude areas. The occurrence and development of non-small cell lung cancer at altitude is not known. Lung cancer is not only the most common malignant tumor in China, but also one of the most common malignant tumors in our high altitude areas. Therefore, it is particularly important to study the correlation between lung cancer and DNA repair gene polymorphism in high altitude areas. Therefore, we chose two genes GTF2H1 and RAD54L2 related to DNA repair to explore their impact on the risk of non-small cell lung cancer in Chinese Han population of living high altitude areas and the efficacy and side effects of platinum chemotherapy.