Article Figures & Data
Tables
- Table 1.
List of studied genes and SNPs
Gene Function Polymorphism dbSNP no. Variant phenotype IL1B Proinflammatory, primary initiator of inflammatory response −31C>T rs1143627 C allele: increased expression (2) Ex5+14C>T rs1143634 IL4 Regulates antibody production, attenuates inflammatory response −584C>T rs2243250 T allele: Increased transcriptional activity (29, 30) −1098G>T rs2243248 IL5 Hematopoietic growth factor, promotes growth and differentiation of eosinophils −745C>T rs2069812 IL6 Proinflammatory, initiator of inflammatory response, growth factor for cancer cells −174C>G rs1800795 G allele: increased expression (31) IL8 Proinflammatory chemokine, activates neutrophils −251A>T rs4073 A allele: increased expression (22) IL10 Anti-inflammatory, regulates T-cell and macrophage function −819C>T rs1800871 In LD with −592 C>A SNP which is linked to reduced expression (27, 28) −1082A>G rs1800896 A allele: reduced expression IL13 Anti-inflammatory, suppresses IL1, IL6, and IL8 production −1069C>T rs1800925 T allele: increased expression (32) IVS3−24T>C rs1295686 LTA Proinflammatory, stimulates prostaglandin synthesis, induces reactive oxygen species production in neutrophils IVS1−82G>C rs746868 IVS1+90G>A rs909253 TNF Proinflammatory, key immunomediator −308A>G rs1800629 A allele: higher transcriptional activation (33, 34) PPARG Anti-inflammatory, tumor suppressor and promoter properties Ex4−49C>G (Pro12Ala) rs1801282 Ala allele: reduced ligand binding (35) PTGS2 Converts arachidonic acid to prostaglandins, thereby promoting inflammatory response −765C>G rs20417 C allele: reduced expression (36) (COX2) Ex3−8G>C rs5277 IVS5−275G>T rs20432 Ex10+837C>T rs5275 - Table 2.
Characteristics of the study population
Characteristic Cases (n = 244) Controls (n = 231) P* Females (%) 22.5 36.4 0.0009† Age (y) 60 (55.5-74.5) 57 (43-71) 0.07 Non-White (%) 11.1 9.1 0.48† Body mass index (kg/m2) 26.5 (21.9-31.2) 25.8 (21.1-30.5) 0.04 Smoking status Current smoker (%) 11.1 4.8 0.01† Regular smoker (y) 26 (6-46) 18 (0-36) 0.0001 Cigarettes per day 20 (0.8-39.2) 20 (0-40) 0.012 NSAID use‡ (%) 51.6 65.4 0.002† Family history of colon cancer (%) 16.8 11.9 0.13† - Table 3.
Genotype distributions and genotypic risks for association with colorectal adenoma for cytokine and other inflammation-related genes
Genotype Cases, n (%) Controls, n (%) OR* (95% CI) IL1B −31 T/T 74 (37.6) 92 (48.2) 1.0 C/T 99 (50.2) 68 (35.6) 1.8 (1.2-2.9) C/C 24 (12.2) 31 (16.2) 0.9 (0.5-1.7) Ptrend = 0.01 C-carrier 123 (62.4) 99 (49.8) 1.5 (1.0-2.3) IL1B Ex5 +14 C/C 131 (59.0) 129 (61.7) 1.0 C/T 78 (35.1) 66 (31.6) 1.1 (0.7-1.7) T/T 13 (5.9) 14 (6.7) 0.9 (0.4-2.0) Ptrend = 0.82 T-carrier 91 (41.0) 80 (38.3) 1.1 (0.7-1.6) IL4 −584 T/T 132 (68) 114 (64.8) 1.0 C/T 53 (27.3) 53 (30.1) 0.9 (0.5-1.4) C/C 9 (4.6) 9 (5.1) 0.8 (0.3-2.6) Ptrend = 0.86 C-carrier 60 (31.9) 62 (35.2) 0.8 (0.5-1.4) IL4 −1098 T/T 177 (84.3) 156 (82.1) 1.0 G/T 33 (15.7) 32 (16.8) 0.9 (0.5-1.5) G/G 0 (0) 2 (1.1) Ptrend = 0.91 G-carrier 33 (15.7) 34 (17.9) 0.9 (0.5-1.5) IL5 −74 C/C 94 (44.8) 82 (43.2) 1.0 C/T 92 (43.8) 85 (44.7) 0.9 (0.6-1.5) T/T 24 (11.4) 23 (12.1) 0.8 (0.4-1.8) Ptrend = 0.90 T-carrier 116 (55.2) 108 (56.8) 0.9 (0.6-1.4) IL6 −174 G/G 79 (38.7) 83 (43.7) 1.0 C/G 90 (44.1) 81 (42.6) 1.1 (0.7-1.8) C/C 35 (17.2) 26 (13.7) 1.5 (0.8-2.9) Ptrend = 0.40 C-carrier 125 (61.3) 107 (56.3) 1.2 (0.8-1.9) IL8 −251 T/T 52 (25.4) 65 (34.0) 1.0 A/T 87 (42.4) 94 (49.2) 1.2 (0.7-1.9) A/A 66 (32.2) 32 (16.8) 2.7 (1.5-4.9) Ptrend = 0.002 A-carrier 153 (74.6) 126 (66.0) 1.5 (1.0-2.4) IL10 −819 C/C 125 (56.3) 117 (56.0) 1.0 C/T 76 (34.2) 79 (37.8) 1.0 (0.6-1.5) T/T 21 (9.5) 13 (6.2) 2.1 (0.9-4.8) Ptrend = 0.19 T-carrier 97 (43.7) 92 (44.0) 1.1 (0.7-1.6) IL10 −1082 A/A 61 (27.5) 55 (26.6) 1.0 A/G 114 (51.4) 123 (59.4) 0.8 (0.5-1.3) G/G 47 (21.1) 29 (14.0) 1.3 (0.7-2.4) Ptrend = 0.17 G-carrier 161 (72.5) 152 (73.4) 0.9 (0.6-1.4) IL13 −1069 C/C 120 (61.5) 102 (59.7) 1.0 C/T 67 (34.4) 58 (33.9) 1.0 (0.6-1.6) T/T 8 (4.1) 11 (6.4) 0.7 (0.2-1.8) Ptrend = 0.69 T-carrier 75 (38.5) 69 (40.3) 1.0 (0.6-1.5) IL13 IVS3 −24 C/C 128 (61.5) 110 (57.0) 1.0 C/T 70 (33.7) 73 (37.8) 0.8 (0.5-1.2) T/T 10 (4.8) 10 (5.2) 0.8 (0.3-2.3) Ptrend = 0.55 T-carrier 80 (37.5) 83 (43.0) 0.8 (0.5-1.2) LTA IVS1 −82 G/G 85 (38.8) 76 (37.1) 1.0 C/G 107 (48.9) 102 (49.8) 1.0 (0.6-1.5) C/C 27 (12.3) 27 (13.1) 0.9 (0.5-1.6) Ptrend = 0.91 C-carrier 134 (61.2) 129 (62.9) 1.0 (0.6-1.4) LTA IVS1+90 A/A 90 (39.8) 88 (42.1) 1.0 A/G 101 (44.7) 92 (44.0) 1.2 (0.8-1.8) G/G 35 (15.5) 29 (13.9) 1.2 (0.7-2.2) Ptrend = 0.71 G-carrier 136 (60.2) 114 (57.9) 1.2 (0.8-1.7) TNF −308 G/G 146 (67.3) 139 (68.8) 1.0 A/G 59 (27.2) 57 (28.2) 1.0 (0.7-1.6) A/A 12 (5.5) 6 (3.0) 1.9 (0.7-5.4) Ptrend = 0.46 A-carrier 71 (32.7) 63 (31.2) 1.1 (0.7-1.7) PPARG −Pro12Ala G/G 153 (77.3) 146 (79.4) 1.0 G/C 41 (20.7) 37 (20.1) 1.1 (0.7-1.8) C/C 4 (2.0) 1 (0.5) 3.2 (0.3-31.1) Ptrend = 0.56 C-carrier 45 (22.7) 38 (21.5) 1.2 (0.7-1.9) PTGS2 −765 G/G 151 (71.9) 141 (71.9) 1.0 G/C 54 (25.7) 52 (26.5) 0.9 (0.6-1.4) C/C 5 (2.4) 3 (1.5) 1.3 (0.3-5.9) Ptrend = 0.85 C-carrier 59 (28.1) 55 (28.0) 0.9 (0.6-1.5) PTGS2 Ex3 −8 G/G 154 (73.3) 142 (72.1) 1.0 G/C 52 (24.8) 51 (25.9) 1.0 (0.6-1.6) C/C 4 (1.9) 4 (2.0) 1.2 (0.3-5.1) Ptrend = 0.97 C-carrier 56 (26.7) 55 (27.9) 1.0 (0.6-1.6) PTGS2 IVS5 −275 T/T 149 (71.0) 136 (69.0) 1.0 T/G 54 (25.7) 57 (28.9) 0.8 (0.5-1.3) G/G 7 (3.3) 4 (2.1) 1.4 (0.4-5.1) Ptrend = 0.53 G-carrier 61 (29.0) 61 (31.0) 0.9 (0.6-1.3) PTGS2 Ex10 +837 C/C 92 (43.8) 77 (39.1) 1.0 T/C 88 (41.9) 102 (51.8) 0.7 (0.5-1.1) T/T 30 (14.3) 18 (9.1) 1.2 (0.6-2.4) Ptrend = 0.16 T-carrier 118 (56.2) 120 (60.9) 0.8 (0.5-1.2) ↵* ORs adjusted for age, sex, and ethnicity.