title: Functional polymorphisms of ITGB1 are associated with clinical outcome of Chinese patients with resected colorectal cancer.
abstract: OBJECTIVE
  Integrin β1 (ITGB1) has been recognized to play a major role in tumor growth, invasion and metastasis. However, effects of single-nucleotide polymorphisms (SNPs) in ITGB1 gene on the prognosis of patients with colorectal cancer (CRC) have not been reported.
  
  
  METHODS
  A total of 372 patients with resected colorectal adenocarcinoma were enrolled in our study. Three functional SNPs (rs2230395, rs1187075 and rs1187076) in ITGB1 were selected and genotyped using the Sequenom iPLEX genotyping system.
  
  
  RESULTS
  We identified two SNPs (rs2230395 and rs1187075) in ITGB1 gene to be significantly associated with CRC overall survival (OS). Compared with the homozygous wild-type (AA) and heterozygous variant (AC), rs2230395 homozygous variant (CC) conferred a 1.55-fold (95 % CI 1.00-2.41, P = 0.049) increased risk of death. Similar result was obtained for homozygous variant (AA) in rs1187075 with a 1.62-fold (95 % CI 1.08-2.42, P = 0.020). In stratified analysis, this association in rs2230395 remained to be significant in patients receiving chemotherapy, but not in those without chemotherapy. We further evaluated the effects of chemotherapy on CRC survival in subgroups stratified by rs2230395 and rs1187075 genotypes. We found that chemotherapy resulted in a significantly better OS in patients with the homozygous wild-type (WW) or heterozygous variant (WV) genotype in both rs2230395 and rs1187075 when compared with patients with homozygous variant (VV) genotype.
  
  
  CONCLUSIONS
  Our data suggest that ITGB1 SNPs might be a prognostic biomarker for CRC patients, especially in those receiving chemotherapy. Our findings warrant validation in larger independent populations.
authors.affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, 169 West Changle Street, Xi'an, 710032, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Huang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yibing
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Liu
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.forename: Xianli
authors.initials: X
authors.lastname: He
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; D019012:Integrin beta1