title: Association between co-inhibitory molecule gene tagging single nucleotide polymorphisms and the risk of colorectal cancer in Chinese.
abstract: OBJECTIVE
  T lymphocyte immune responses are controlled by both co-stimulatory and co-inhibitory signaling through T cell co-receptors. Cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death 1 (PD-1) and B and T lymphocyte attenuator (BTLA) are all co-inhibitory molecules that negatively regulate the activation of T cells. In this study, we investigated the relationship between ten tagging SNPs in three co-inhibitory molecule genes and colorectal cancer (CRC).
  
  
  METHODS
  We conducted a hospital-based case-control study consisting of 601 cases with CRC and 627 CRC-free individuals from the Heilongjiang Province of China.
  
  
  RESULTS
  The rs7421861 CT genotype was significantly associated with the risk of colorectal cancer compared to the wild-type TT genotype (adjusted OR 1.314, 95% CI 1.012-1.706, P = 0.041). The rs2705535 TT genotype was associated with the risk of rectal cancer [OR 1.819 (1.093-3.027), P = 0.021]. There was statistical interaction between the PD-1/rs2227982 (CT + TT) genotypes and high seafood intake (>once/week), as well as the CTLA-4/rs231777 variant and high pungent food intake (>3 times/week). The AG + AA genotypes of CTLA-4/rs3087243 statistically and antagonistically interacted with soybeans, pork and alcohol intake and were associated with CRC risk. Analogously, BTLA/rs1844089 interacted with pork intake, PD-1/rs7421861 with beef and lamb consumption and PD-1/rs6710479 with barbecue consumption. Haplotype G-C-G-A-T-T-A was significantly associated with CRC risk (OR 1.221 P = 0.034).
  
  
  CONCLUSIONS
  These data indicate potential associations between BTLA and PD-1 polymorphisms and CRC susceptibility. Additionally, the three co-inhibitory molecule gene SNPs have environmental interactions associated with CRC risk.
authors.affiliation: Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ge
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Junde
authors.initials: J
authors.lastname: Zhou
authors.forename: Guangxiao
authors.initials: G
authors.lastname: Li
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.forename: Shuying
authors.initials: S
authors.lastname: Li
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wu
authors.forename: Jiesheng
authors.initials: J
authors.lastname: Rong
authors.forename: Huiping
authors.initials: H
authors.lastname: Yuan
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chi
authors.forename: Daxun
authors.initials: D
authors.lastname: Piao
authors.forename: Yashuang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Binbin
authors.initials: B
authors.lastname: Cui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: C482586:BTLA protein, human; D060908:CTLA-4 Antigen; D061025:Costimulatory and Inhibitory T-Cell Receptors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic