title: Correlation of chitinase 3-like 1 single nucleotide polymorphisms and haplotypes with uterine cervical cancer in Taiwanese women.
abstract: BACKGROUND
  This study aimed to investigate the relationships of chitinase 3-like 1 (CHI3L1) single nucleotide polymorphisms (SNPs) and haplotypes with the development of uterine cervical cancer in Taiwanese women. The SNPs frequencies and haplotypes were also correlated with the clinicopathologic variables of cervical cancer, cancer recurrence, and patient survival.
  
  
  RESULTS
  Ninety-nine patients with invasive cancer and 61 with pre-cancerous lesions of the uterine cervix were compared to 310 healthy control subjects. Three SNPs rs6691378 (-1371, G/A), rs10399805 (-247, G/A) and rs4950928 (-131, C/G) in the promoter region, and one SNP rs880633 (+2950, T/C) in exon 5 were analyzed by real time polymerase chain reaction and genotyping. The results showed that the mutant homozygous genotype AA of CHI3L1 SNP rs6691378 and AA of rs10399805, and haplotypes AACC and AACT increased the risk of developing pre-cancerous lesions and invasive cancer. The patients with these risk haplotypes had higher than stage I tumors, larger tumors, and vaginal invasion. In logistic regression model, they also tended to have poor survival event [p = 0.078; odds ratio (OR): 2.99, 95% confidence interval (CI): 0.89-10.08] and a higher probability of recurrence event (p = 0.081; OR: 3.07, 95% CI: 0.87-10.81). There was a significant association between the CHI3L1 risk haplotypes and probability of recurrence (p = 0.002; hazard ratio: 6.21, 95% CI: 1.90-20.41), and a marginal association between the risk haplotypes and overall survival (p = 0.051; hazard ratio: 3.76, 95% CI: 0.99-14.29) in the patients with SCC, using Cox proportional hazard model.
  
  
  CONCLUSIONS
  The CHI3L1 SNPs rs6691378 and rs10399805 and CHI3L1 haplotypes all correlated with the development of cervical pre-cancerous lesions and invasive cancer. The cervical cancer patients with the CHI3L1 haplotypes AACC or AACT had poor clinicopathologic characteristics and poor recurrence and survival events. These risk haplotypes were associated with higher recurrence, especially in the patients with SCC.
authors.affiliation: Department of Obstetrics and Gynecology, Chi-Mei Foundation Medical Center, Tainan, Taiwan.
authors.forename: Yue-Shan
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ying-Erh
authors.initials: YE
authors.lastname: Chou
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Cardiology, Department of Internal Medicine, Yuan-Sheng Hospital and Changhua Christian Hospital, Yuanlin Branch, Yuanlin, Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chao-Wen
authors.initials: CW
authors.lastname: Cheng
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Po-Hui
authors.initials: PH
authors.lastname: Wang
mesh_terms: D054392:Adipokines / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics*; D000071451:Chitinase-3-Like Protein 1; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D037102:Lectins / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins