Table 2.
Molecular biomarkers associated with CRC chemopreventive agent effects. Abbreviations: 15-PGDH, 15-hydroxyprostaglandin dehydrogenase; APC, Adenoma Prevention with Celecoxib; CCFR, Colon Cancer Family Registry; COX-2, cyclooxygenase 2; CRC, colorectal cancer; GSEC, Genetic Susceptibility to Environmental Carcinogens; GWAS, genome-wide association study; HPFS, Health Professionals Follow-up Study; MECC, Molecular Epidemiology of Colorectal Cancer; MIC1, macrophage inhibitory cytokine 1; MSI, microsatellite instability; NHS, Nurses’ Health Study; PGE-M, prostaglandin E2 major metabolite; PI3KCA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; RCT, randomized controlled trial; SNP, single-nucleotide polymorphism; sTNFR-2, serum soluble tumor necrosis factor receptor-2; UGT1A6, UDP glucuronosyltransferase family 1 member A6.
| Biomarker | Type | Chemopreventive Agent | Study (Number of Participants) | Endpoint | Description | Outcome | Ref |
|---|---|---|---|---|---|---|---|
| rs2070959-G | Genetic variant | Aspirin | NHS (1062) | CRC | G genotype SNP | Protective against CRC | [69,70] |
| rs4365457-C | Genetic variant | Aspirin | NHS (1062) | CRC | C genotype SNP | Protective against CRC | [69,70] |
| rs2430420-GG | Genetic variant | Low-dose aspirin | AFFPS nested cohorts within an RCT (370) | Adenoma | GG genotype SNP | Protective against CRC | [71] |
| rs28362380-TT | Genetic variant | Low-dose aspirin | AFFPS nested cohorts within an RCT (370) | Adenoma | TT genotype SNP | Protective against CRC | [71] |
| PGE-M | Urine levels | Aspirin | NHS and AFPPS (748) | Adenoma | High levels | Protective against CRC | [72] |
| rs2920421-GA | Genetic variation | Aspirin | CCFR (1621) |
CRC | GA genotype SNP | Protective against CRC | [73] |
| sTNFR-2 | Plasma levels | Aspirin | NHS (280) | CRC | High levels | Protective against CRC | [74] |
| MIC1 | Plasma levels | Aspirin | NHS and HPFS (618) | CRC | High levels | Promotes COX-2-positive CRC | [75] |
| COX-2 | Overexpression in tumor | Aspirin | NHS and HPFS (632) | CRC | High levels | Protective against CRC | [76,77] |
| PIK3CA | Mutation in tumor | Aspirin | NHS and HPFS (2190) | CRC | PIK3CA exons 9 and 20 mutated in tumor | Protective against CRC | [78] |
| BRAF | Mutation in tumor | Aspirin | NHS and HPFS (1226) | CRC | BRAF V600E mutated in tumor | Promotes CRC | [79] |
| rs6983267-T | Genetic variant | Aspirin | NHS and HPFS (840) | CRC | T genotype SNP | Protective against CRC | [83,84] |
| 15-PGDH | Colon mucosa levels | Aspirin | NHS and HPFS (270) | CRC | High levels | Protective against CRC | [85] |
| rs2965667-TT | Genetic variant | Aspirin | GWAS (8,634) | CRC | TT genotype SNP | Protective against CRC | [86] |
| rs16973225-AA | Genetic variant | Aspirin | GWAS (8,634) | CRC | AA genotype SNP | Protective against CRC | [86] |
| rs1057910-C | Genetic variant | Celecoxib | APC (2,035) | Adenoma | C genotype SNP | Protective against CRC | [98] |
| rs12654264-AA | Genetic variant | Statins | MECC (4,187) | CRC | AA genotype SNP | Protective against CRC | [154] |
| MTHFR 677TT | Genetic variant | Folic acid | GSEC (30,650) | CRC | TT genotype SNP | Protective against CRC | [181,182,183] |
| MSI | Microsatellite instability | Hormone replacement therapy (estrogen and progestin) | Case-control studies | CRC | MSI-low or stable tumors | Protective against CRC | [243] |