Association between genetic polymorphisms and carotid atherosclerosis in patients treated with radiotherapy for nasopharyngeal carcinoma

详细信息    查看全文

• 作者：Chuang Yuan ; Shea Ping Yip ; Vincent WC Wu ; Dora LW Kwong…
• 关键词：Radiation ; Nasopharyngeal carcinoma ; Carotid atherosclerosis ; Carotid plaque score ; Single nucleotide polymorphisms ; Paraoxonase
• 刊名：Radiation Oncology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：10
• 期：1
• 全文大小：1,058 KB
• 参考文献：1. Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomark Prev. 2006;15:1765-7. CrossRef
  2. Lu H, Yao M. The current status of intensity-modulated radiation therapy in the treatment of nasopharyngeal carcinoma. Cancer Treat Rev. 2008;34:27-6. CrossRef
  3. Muzaffar K, Collins SL, Labropoulos N, Baker WH. A prospective study of the effects of irradiation on the carotid artery. Laryngoscope. 2000;110:1811-. CrossRef
  4. Lam WW, Leung SF, So NM, Wong KS, Liu KH, Ku PK, et al. Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy. Cancer. 2001;92:2357-3. CrossRef
  5. Lam WW, Yuen HY, Wong KS, Leung SF, Liu KH, Metreweli C. Clinically underdetected asymptomatic and symptomatic carotid stenosis as a late complication of radiotherapy in Chinese nasopharyngeal carcinoma patients. Head Neck. 2001;23:780-. CrossRef
  6. Li CS, Schminke U, Tan TY. Extracranial carotid artery disease in nasopharyngeal carcinoma patients with post-irradiation ischemic stroke. Clin Neurol Neurosurg. 2010;112:682-. CrossRef
  7. Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: A comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med. 2002;33:337-9. CrossRef
  8. He SQ, Zhang YH, Venugopal SK, Dicus CW, Perez RV, Ramsamooj R, et al. Delivery of antioxidative enzyme genes protects against ischemia/reperfusion-induced liver injury in mice. Liver Transpl. 2006;12:1869-9. CrossRef
  9. Aviram M, Rosenblat M. Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med. 2004;37:1304-6. CrossRef
  10. Li AC, Binder CJ, Gutierrez A, Brown KK, Plotkin CR, Pattison JW, et al. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/delta, and gamma. J Clin Invest. 2004;114:1564-6. CrossRef
  11. Wolf AM, Wolf D, Rumpold H, Enrich B, Tilg H. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem Biophys Res Commun. 2004;323:630-. CrossRef
  12. Wakkach A, Cottrez F, Groux H. Can interleukin-10 be used as a true immunoregulatory cytokine? Eur Cytokine Netw. 2000;11:153-0.
  13. Wahl SM, Wen J, Moutsopoulos N. TGF-beta: a mobile purveyor of immune privilege. Immunol Rev. 2006;213:213-7. CrossRef
  14. Napoli C, Ignarro LJ. Polymorphisms in endothelial nitric oxide synthase and carotid artery atherosclerosis. J Clin Pathol. 2007;60:341-. CrossRef
  15. Kakko S, Paivansalo M, Koistinen P, Kesaniemi YA, Kinnula VL, Savolainen MJ. The signal sequence polymorphism of the MnSOD gene is associated with the degree of carotid atherosclerosis. Atherosclerosis. 2003;168:147-2. CrossRef
  16. Casas JP, Bautista LE, Humphries SE, Hingorani AD. Endothelial nitric oxide synthase genotype and ischemic heart disease - Meta-analysis of 26 studies involving 23028 subjects. Circulation. 2004;109:1359-5. CrossRef
• 刊物主题：Oncology; Radiotherapy;
• 出版者：BioMed Central
• ISSN：1748-717X

文摘

Background Radiotherapy (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. Methods The 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. Results rs662 and rs705379 of PON1 were close to be significantly associated with carotid plaque score (Corrected P value, P cor --.0528 and P cor --.0842). When the two SNPs were combined together, TC haplotype in rs662-rs705379 of PON1 was significantly associated with higher carotid plaque score (P cor --.05). None of the other SNPs showed significant association with carotid plaque score. Conclusions TC 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.