Genetic variation in prostaglandin synthesis and related pathways, NSAID use and colorectal cancer risk in the Colon Cancer Family Registry (original) (raw)

“…For example, several gene-by-environment (GxE) interaction analyses have been pursued that focus on genetic variants associated with PG or aspirin function 54,89–93 ; however, few of these studies have demonstrated a significant interaction between aspirin use and genetic variants in the context of CRC or adenoma risk. One cohort study did observe that the GA genotype of the single nucleotide polymorphism (SNP) rs2920421, which lies in an intronic region of ALOX12 (which encodes arachidonate 12-lipoxygenase), was associated with a lower risk of CRC only among current NSAID users and not among never users or former users 94 . This finding requires corroboration in other populations as candidate-gene-based approaches to GxE interaction studies have a high potential for false-positive results.…”

Section: Molecular Risk Stratificationmentioning

“…For example, several gene-by-environment (GxE) interaction analyses have been pursued that focus on genetic variants associated with PG or aspirin function 54,89–93 ; however, few of these studies have demonstrated a significant interaction between aspirin use and genetic variants in the context of CRC or adenoma risk. One cohort study did observe that the GA genotype of the single nucleotide polymorphism (SNP) rs2920421, which lies in an intronic region of ALOX12 (which encodes arachidonate 12-lipoxygenase), was associated with a lower risk of CRC only among current NSAID users and not among never users or former users 94 . This finding requires corroboration in other populations as candidate-gene-based approaches to GxE interaction studies have a high potential for false-positive results.…”

Section: Molecular Risk Stratificationmentioning

“…Leukotrienes are important for immune cell signaling and differentiation, while prostaglandins have various homeostatic, developmental, and immune related functions [69,70]. Although both COX-1 and COX-2 produce the shortlived intermediate PGH 2 , COX-1 is generally coupled with homeostatic prostaglandin (PG) levels, while COX-2 and mPGES-1 are associated with inducible levels of PGE 2 production [55,71]. Therefore, in the context of disease, COX-2 and mPGES-1 are generally accepted as the cyclooxygenase and synthase associated with pathogenic PG production.…”

Section: Mir-708 Suppresses Pge 2 Production By Targeting the Cox-2 And Mpges-1 3′ Utrsmentioning

“…One of the ALOX12 SNPs that was associated with differential colorectal polyp prevention activity of aspirin in our study (the intronic SNP rs2920421) has been reported to interact with NSAID use in a case–control study of colorectal cancer risk ( 26 ). In that study, NSAID use was associated with decreased colorectal cancer risk in heterozygous rs2920421 genotypes, but not major or minor homozygotes ( 26 ).…”

Section: Discussionmentioning