PURPOSE: 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.
PURPOSE: 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: K M Lee; E Chuang; M Griffin; R Khattri; D K Hong; W Zhang; D Straus; L E Samelson; C B Thompson; J A Bluestone Journal: Science Date: 1998-12-18 Impact factor: 47.728
Authors: P M Marcus; R B Hayes; P Vineis; M Garcia-Closas; N E Caporaso; H Autrup; R A Branch; J Brockmöller; T Ishizaki; A E Karakaya; J M Ladero; S Mommsen; H Okkels; M Romkes; I Roots; N Rothman Journal: Cancer Epidemiol Biomarkers Prev Date: 2000-05 Impact factor: 4.254