title: Genetic polymorphisms of the CASP8 gene promoter may not be associated with colorectal cancer in Han Chinese from southwest China.
abstract: OBJECTIVE
  Caspase 8 (CASP8) plays a critical role in the apoptotic pathway and aberrant regulation of this pathway causes many diseases including cancers. Genetic variants rs3834129 (CTTACT/-) and rs3769821 (T/C) in the promoter region of the CASP8 gene were documented to be associated with multiple solid cancers and non-Hodgkin's lymphoma (NHL), respectively, despite of some controversies. We aimed to discern potential association of these two variants and rs113686495 (CTGTCATT/-), as well as CASP8 mRNA and protein expression levels with colorectal cancer (CRC) in Han Chinese.
  
  
  METHODS
  We genotyped CASP8 genetic variants in 305 CRC patients and 342 healthy individuals from Kunming, Southwest China. Expression levels of CASP8 mRNA and protein were quantified in paired cancerous and paracancerous normal tissues by using real-time quantitative PCR and western blot, respectively. We compared the frequencies of alleles, genotypes, and haplotypes between the cases and controls. Correlation of CASP8 mRNA and protein expression levels in paired cancerous and paracancerous normal tissues from patients with different genotypes and clinical expression were also evaluated.
  
  
  RESULTS
  There was no association of the CASP8 genetic variants with CRC in our case-control study. The CASP8 gene mRNA expression levels in cancerous and paracancerous normal tissues were similar and there was no significant difference between subjects with different genotypes and clinical features. However, we found that CASP8 protein level was significantly lower in cancerous tissues than in paired paracancerous normal tissues.
  
  
  CONCLUSIONS
  Our results suggest that the three CASP8 genetic variants may not be associated with CRC risk in Han Chinese from southwest China. Aberrant CASP8 protein expression may play a role in the pathogenesis of CRC.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, China.
authors.forename: Mei-Sheng
authors.initials: MS
authors.lastname: Xiao
authors.forename: Le
authors.initials: L
authors.lastname: Chang
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Li
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Du
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wen
authors.forename: Juan
authors.initials: J
authors.lastname: Luo
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; C505530:CASP8 protein, human; D053181:Caspase 8