title: Genetic variations in stem cell-related genes and colorectal cancer prognosis.
abstract: BACKGROUND
  Many properties of cancer cells are reminiscent of those in normal stem cells. Genes important to stem cell development have been significantly implicated in the etiology and clinical outcome of colorectal cancer (CRC). However, the associations of genetic variations in these genes with CRC prognosis have not yet been elucidated.
  
  
  METHODS
  We analyzed the effects of eight potentially functional single nucleotide polymorphisms (SNPs) in six stem cell-related genes on the prognosis of a well-characterized population of 380 Chinese CRC patients diagnosed from February 2006 to January 2010.
  
  
  RESULTS
  The most significant finding was related to rs879882, a variant in the 5' region of POU5F1 gene which encodes a protein essential for embryonic stem cell self-renewal and pluripotency, and induced pluripotent stem cell reprogramming. The variant-containing genotypes of rs879882 were associated with an increased risk of recurrence (hazard ratio [HR] = 2.10, 95% confidence interval [CI] 1.17-3.76, P = 0.01). In chemotherapy-stratified analysis, the association remained borderline significant in patients receiving chemotherapy (HR = 1.97, 95% CI 0.89-4.34, P = 0.09). In addition, a nonsynonymous SNP of APC gene was also significantly associated with recurrence risk in chemotherapy-treated patients (HR = 2.63, 95% CI 1.14-6.06 P = 0.02). Further analyses showed a combined effect of the two SNPs in predicting CRC recurrence in patients receiving chemotherapy (P = 0.04) but not in those without chemotherapy (P = 0.43). Moreover, an exploratory multivariate assessment model indicated that these two variants enhanced the power to predict recurrence after chemotherapy.
  
  
  CONCLUSIONS
  We presented one of the first epidemiologic studies showing that stem cell-related genetic variants may impact CRC clinical outcomes, especially in chemotherapy-treated patients.
authors.affiliation: Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, 1025 Walnut Street, Room 1015, Philadelphia, PA 19107, USA. hushan.yang@jefferson.edu
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.forename: Falin
authors.initials: F
authors.lastname: Qu
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Myers
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Bao
authors.forename: Terry
authors.initials: T
authors.lastname: Hyslop
authors.forename: Guang
authors.initials: G
authors.lastname: Hu
authors.forename: Fei
authors.initials: F
authors.lastname: Fei
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D013234:Stem Cells / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C092069:activity regulated cytoskeletal-associated protein