Genetic Variants in Inflammation-Related Genes Are Associated with Radiation-Induced Toxicity Following Treatment for Non-Small Cell Lung Cancer
نویسندگان
چکیده
Treatment of non-small cell lung cancer (NSCLC) with radiotherapy or chemoradiotherapy is often accompanied by the development of esophagitis and pneumonitis. Identifying patients who might be at increased risk for normal tissue toxicity would help in determination of the optimal radiation dose to avoid these events. We profiled 59 single nucleotide polymorphisms (SNPs) from 37 inflammation-related genes in 173 NSCLC patients with stage IIIA/IIIB (dry) disease who were treated with definitive radiation or chemoradiation. For esophagitis risk, nine SNPs were associated with a 1.5- to 4-fold increase in risk, including three PTGS2 (COX2) variants: rs20417 (HR:1.93, 95% CI:1.10-3.39), rs5275 (HR:1.58, 95% CI:1.09-2.27), and rs689470 (HR:3.38, 95% CI:1.09-10.49). Significantly increased risk of pneumonitis was observed for patients with genetic variation in the proinflammatory genes IL1A, IL8, TNF, TNFRSF1B, and MIF. In contrast, NOS3:rs1799983 displayed a protective effect with a 45% reduction in pneumonitis risk (HR:0.55, 95% CI:0.31-0.96). Pneumonitis risk was also modulated by polymorphisms in anti-inflammatory genes, including genetic variation in IL13. rs20541 and rs180925 each resulted in increased risk (HR:2.95, 95% CI:1.14-7.63 and HR:3.23, 95% CI:1.03-10.18, respectively). The cumulative effect of these SNPs on risk was dose-dependent, as evidenced by a significantly increased risk of either toxicity with an increasing number of risk genotypes (P<0.001). These results suggest that genetic variations among inflammation pathway genes may modulate the development of radiation-induced toxicity and, ultimately, help in identifying patients who are at an increased likelihood for such events.
منابع مشابه
Inflammation-related genetic variants predict toxicities following definitive-radiotherapy for lung cancer
Definitive radiotherapy improves locoregional control and survival in inoperable non-small cell lung cancer patients. However, radiation-induced toxicities (pneumonitis/esophagitis) are common dose-limiting inflammatory conditions. We therefore conducted a pathway-based analysis to identify inflammation-related single-nucleotide polymorphisms associated with radiation-induced pneumonitis or eso...
متن کاملMiR-96 induced non-small-cell lung cancer progression through competing endogenous RNA network and affecting EGFR signaling pathway
Objective(s): Non-small cell lung cancer (NSCLC) has become a serious global health problem in the 21st century, and tumor proliferation and metastasis are the leading causes of death in patients with lung cancer. The present study aimed to verify the function of miR-96 and miR-96 in relation to competing with endogenous RNA regulatory network in NSCLC progression inc...
متن کاملA review of the role of dopamine receptors and novel therapeutic strategies in non-small cell lung cancer (NSCLC)
Lung cancer is a very aggressive and most deadly cancer in both men and women. Lung cancer is divided into two types of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC is divided into 3 subgroups: adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large cell carcinoma (LCC). Dopamine is involved in controlling motions, cognition, emotions, memory and reward mech...
متن کاملInherent radiosensitivity and its impact on breast cancer chemo-radiotherapy
About 10% of apparently normal individuals are sensitive to clastogenic effects of physico-chemical agents. More than 45% of breast cancer patients’ exhibit elevated radiosensitivity. Although the nature of inherent radiosensitivity is not fully understood, but insufficiency and impaired DNA repair mechanism might be prime cause of radiosensitivity. This is evident from genetically affect...
متن کاملAtorvastatin Sensitizes Breast and Lung Cancer Cells to Ionizing Radiation
Tumour cells may be resistant to radiotherapy that results in unsuccessful cancer treatment in patients. The aim of this study was to evaluate the sensitizing effect of atorvastatin (ATV) on breast cancer (MDA-MB-231) and non-small cell lung cancer (A-549) cells following exposure to ionizing radiation (IR). These cells were treated with ATV and exposed to X-ray at dose 4 Gy. The radiosensitizi...
متن کامل