title: Association between genetic polymorphisms and carotid atherosclerosis in patients treated with radiotherapy for nasopharyngeal carcinoma.
abstract: 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  =0.0528 and P cor  =0.0842). When the two SNPs were combined together, TC haplotype in rs662-rs705379 of PON1 was significantly associated with higher carotid plaque score (P cor  < 0.05). 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.
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR, China. aeolus.yc@connect.polyu.hk.|Current address: Medical Research Center, Changsha Central Hospital, Changsha, Hunan, China. aeolus.yc@connect.polyu.hk.
authors.forename: Chuang
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR, China. shea.ping.yip@polyu.edu.hk.
authors.forename: Shea Ping
authors.initials: SP
authors.lastname: Yip
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR, China. vincent.wu@polyu.edu.hk.
authors.forename: Vincent W C
authors.initials: VW
authors.lastname: Wu
authors.affiliation: Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong, SAR, China. dlwkwong@hkucc.hku.hk.
authors.forename: Dora L W
authors.initials: DL
authors.lastname: Kwong
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR, China. isa.cheuk@connect.polyu.hk.
authors.forename: Isabella W Y
authors.initials: IW
authors.lastname: Cheuk
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR, China. htmying@polyu.edu.hk.
authors.forename: Michael
authors.initials: M
authors.lastname: Ying
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000209:etiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D015415:Biomarkers