title: GWAS-identified colorectal cancer susceptibility locus associates with disease prognosis.
abstract: OBJECTIVE
  Extensive evidence has suggested that risk factors of cancer development may also modulate cancer clinical outcome. Recent genome-wide association (GWA) studies identified several single nucleotide polymorphisms (SNPs) predisposing to colorectal cancer (CRC). Given the pivotal importance of these variants in CRC, we sought to evaluate their associations with clinical outcomes of the disease.
  
  
  METHODS
  In a well-characterised cohort including 380 Chinese CRC patients, we genotyped seven SNPs identified in previous multi-stage GWA studies and analysed their associations with patient recurrence and survival.
  
  
  RESULTS
  One SNP on chromosome 15q13, rs4779584 was associated with reduced risk of death with a hazard ratio (HR) of 0.33 (95% confidence interval [CI] 0.15-0.72, P = 0.007). Another SNP in a gene-desert region on chromosome 10p14, rs10795668, was associated with a reduced risk of recurrence with an HR of 0.55 (95% CI 0.30-1.00, P = 0.05). In a stratified analysis, this association was only evident in patients receiving chemotherapy (HR = 0.32, 95% CI 0.14-0.78, P = 0.01, log rank P = 0.004), but not in those without chemotherapy (HR = 1.08, 95% CI 0.43-2.73, P = 0.87, log rank P = 0.66). Moreover, we found that the effects of chemotherapy on CRC recurrence was only evident in patients with the variant-containing genotypes (HR = 0.35, 95% CI 0.13-0.94, P = 0.04) but not in those with the wild-type genotype of rs10795668. Further analyses indicated a borderline significant interaction effect (P interaction = 0.05) between rs10795668 and chemotherapy on patient recurrence.
  
  
  CONCLUSIONS
  Our data suggested that rs10795668, a CRC susceptibility variant identified by GWA studies, might be used as a biomarker to identify CRC patients with high risk of recurrence after chemotherapy.
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Centre, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Myers
authors.forename: Xianli
authors.initials: X
authors.lastname: He
authors.forename: Falin
authors.initials: F
authors.lastname: Qu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Xi
authors.initials: X
authors.lastname: Ma
authors.forename: Terry
authors.initials: T
authors.lastname: Hyslop
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Bao
authors.forename: Shaogui
authors.initials: S
authors.lastname: Wan
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012306:Risk; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers