Abstract
BackgroundRadiotherapy (RT) of the neck is commonly given to nasopharyngeal carcinoma (NPC) patients for preventing cervical lymph node metastasis. However, neck RT may induce the development of carotid atherosclerosis. The mechanisms of radiation-induced carotid atherosclerosis are still unclear and no previous study has investigated the genetic involvement of radiation-induced carotid atherosclerosis. The present study aims to determine the association between genetic polymorphisms and carotid atherosclerosis in patients treated with RT for nasopharyngeal carcinoma.MethodsThe present study recruited 128 post-RT NPC patients. Carotid plaque score was assessed using ultrasonography. Thirteen single nucleotide polymorphisms (SNPs) that affect the function of anti-atherosclerotic genes, including SOD2, SOD3, CAT, PON1, PPARG, ADIPOQ, IL10, TGFB1 and NOS3, were genotyped. Association between the 13 SNPs and carotid atherosclerosis was evaluated using multiple regression after adjustment for covariates (PLINK). Multiple testing was corrected using Benjamini-Hochberg step-up false discovery rate controlling procedure.Resultsrs662 and rs705379 of PON1 were close to be significantly associated with carotid plaque score (Corrected P value, Pcor = 0.0528 and Pcor = 0.0842). When the two SNPs were combined together, TC haplotype in rs662-rs705379 of PON1 was significantly associated with higher carotid plaque score (Pcor < 0.05). None of the other SNPs showed significant association with carotid plaque score.ConclusionsTC haplotype in rs662-rs705379 of PON1 is likely to be a genetic risk factor of carotid plaque score. Post-RT NPC patients with the TC haplotype may need earlier and more frequent carotid ultrasound examinations for early detection of carotid atherosclerosis.
Highlights
Radiotherapy (RT) of the neck is commonly given to nasopharyngeal carcinoma (NPC) patients for preventing cervical lymph node metastasis
Demographic information A total of 128 post-RT NPC patients were included in the present study
In the 13 single nucleotide polymorphisms (SNPs), only rs662 and rs705379 in Paraoxonase 1 (PON1) were close to be significantly associated with carotid plaque score in post-RT NPC patients
Summary
Radiotherapy (RT) of the neck is commonly given to nasopharyngeal carcinoma (NPC) patients for preventing cervical lymph node metastasis. Neck RT may induce the development of carotid atherosclerosis. The present study aims to determine the association between genetic polymorphisms and carotid atherosclerosis in patients treated with RT for nasopharyngeal carcinoma. Owing to the high prevalence of cervical lymph node metastasis in NPC patients, RT of the neck is usually given to the patients for preventing or treating the nodal metastasis [2]. The mechanisms of radiation-induced carotid atherosclerosis are still unknown. The mechanisms of spontaneous atherosclerosis are well established, which provide baseline information for the understanding of the mechanisms of radiation-induced carotid atherosclerosis. Different pathways in the regulation of oxidative stress, lipid metabolisms, and inflammation may protect the carotid artery from atherosclerosis. Superoxide dismutases (SODs) are the primary enzymes in the defense of oxidative stress, which
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