Predictive SNPs for radiation-induced damage in lung cancer patients with radiotherapy: a potential strategy to individualize treatment

Abstract

In the treatment of lung cancer, radiotherapy has become one of the most important therapies, despite its sometimes unpredictable side effects. As such, identifying lung cancer patients who are at high risk of developing severe radiation-induced damage (mainly radiation pneumonitis and radiation-induced esophageal toxicity) and applying effect intervention or monitoring techniques are important. Although human diversity to a certain amount is explained by clinical and dosimetric factors, the presence of specific genetic determinants also influences the occurrence of radiation-induced damage. Here we summarize the data on mechanisms of radiation pneumonitis and radiation-induced esophageal toxicity supporting the involvement of variances of genes in the evolution of radiation-induced damage. Furthermore, the available evidence from current clinical studies of genetic polymorphisms for the prediction of radiation pneumonitis and radiation-induced esophageal toxicity is discussed. Eventually, this may help to truly individualize radiotherapy, using a personal genetic profile of the most relevant genes for each lung cancer patient.

Association between ATM gene polymorphisms, lung cancer susceptibility and radiation-induced pneumonitis: a meta-analysis

“…DNA repair pathways are activated after DNA damage, especially DNA DSBs [ 20 ]. Individuals with impaired DNA repair pathways have high sensitivity to radiation exposure and therefore a higher risk of lung cancer and RP [ 8 , 20 ]. Previous studies have suggested that the ATM gene plays a critical role in DNA damage repair and thereby affects the risk of lung cancer and RP.…”

“…Approximately half of patients with RP die [ 5 – 7 ]. RP is a common dose-limiting toxicity of radiotherapy [ 8 ]. Its risk factors include patient-related factors, such as gender, smoking and pulmonary function, and treatment-related factors, such as the radiation dose and irradiated lung volume, and whether surgery or chemotherapy was performed [ 9 – 11 ].…”

“…Polymorphisms in ATM may influence the structure and function of the protein, leading to defects in the activation of cell cycle checkpoints, DNA DSB repair, and cell apoptosis. Additionally, ATM gene mutations may alter the radiosensitivity of cells [ 8 , 20 , 21 ]. The development of cancers and radiation- induced side effects, including pneumonitis, is often linked to these abnormal cells [ 20 , 22 ].…”

Association of DNA repair gene polymorphisms with the risk of radiation pneumonitis in lung cancer patients

“…Single-nucleotide polymorphisms (SNPs) have been proposed as a potential predictive biomarker for the development of RP. SNPs in inflammation, DNA repair, stress response and angiogenesis-related genes were proved to be associated with RP, with different underlying mechanisms [ 14 ].…”

Precision Radiotherapy and Radiation Risk Assessment: How Do We Overcome Radiogenomic Diversity?

“…With radiotherapy, only a subset of any patient population will develop radiosensitivity-related normal tissue damage; however, little information is available to identify those individuals in advance. Furthermore, earlier searches for clinical biomarkers associated with radiotherapy toxicity were hindered by the use of multiple and different endpoints (such as acute radiation syndrome (Dörr and Meineke 2011), radiation pneumonitis (Huang et al 2015), radiation dermatitis (Borghini et al 2014), and radiationrelated secondary carcinogenesis (Brenner et al 2003)), which created confusion. Consequently, today's standard protocols are designed using doses that minimize the incidence of severe adverse effects, based on all patients (Kerns et al 2014).…”