Table 3

Joint effect between gene promoter region methylation and different cancer stages for cancer recurrence in patients with colorectal cancer

Normal tissuesTumor tissues
Recurrence in different stages by methylationNumber of participantsNumber of cases (%)Crude OR (95% CI)Adjusted OR (95% CI)Number of participantsNumber of cases (%)Crude OR (95% CI)Adjusted OR (95% CI)
CDKN2A
 UnMe/local (1 and 2)*557 (12.7)1.00 (referent)1.00 (referent)445 (11.4)1.00 (referent)1.00 (referent)
 UnMe/advanced (3 and 4)†5325 (47.2)6.12 (2.35 to 15.97)5.40 (1.99 to 14.62)3214 (43.8)6.07 (1.89 to 19.43)4.95 (1.46 to 16.83)
 Me/local (1 and 2)‡151 (6.7)0.49 (0.06 to 4.33)0.50 (0.06 to 4.47)263 (11.5)1.02 (0.22 to 4.66)1.09 (0.23 to 5.23)
 Me/advanced (3 and 4)§98 (88.9)54.86 (5.93 to 507.60)34.40 (3.51 to 336.99)3019 (63.3)13.47 (4.10 to 44.30)12.21 (3.38 to 44.11)
 p Value¶<0.0010.002<0.001<0.001
MLH1
 UnMe/local (1 and 2)*688 (11.8)1.00 (referent)1.00 (referent)577 (12.3)1.00 (referent)1.00 (referent)
 UnMe/advanced (3 and 4)†5931 (52.5)8.30 (3.38 to 20.37)6.74 (2.61 to 17.38)5429 (53.7)8.29 (3.19 to 21.53)6.81 (2.49 to 18.65)
 Me/local (1 and 2)‡20 (0.0)NA**NA**131 (7.7)0.60 (0.07 to 5.31)0.62 (0.07 to 5.72)
 Me/advanced (3 and 4)§32 (66.7)15.00 (1.22 to 184.81)10.81 (0.83 to 140.40)84 (50.0)7.14 (1.45 to 35.23)5.85 (1.12 to 30.47)
 p Value¶0.0350.0690.0160.036
MGMT
 UnMe/local (1 and 2)*677 (10.4)1.00 (referent)1.00 (referent)404 (10.0)1.00 (referent)1.00 (referent)
 UnMe/advanced (3 and 4)†5629 (51.8)9.21 (3.59 to 23.62)7.41 (2.75 to 19.97)3320 (60.6)13.85 (3.98 to 48.18)9.64 (2.61 to 35.62)
 Me/local (1 and 2)‡31 (33.3)4.29 (0.34 to 53.53)2.62 (0.20 to 34.19)304 (13.3)1.38 (0.32 to 6.05)1.15 (0.26 to 5.17)
 Me/advanced (3 and 4)§64 (66.7)17.14 (2.64 to 111.14)13.90 (2.03 to 95.21)2913 (44.8)7.31 (2.06 to 25.93)6.12 (1.66 to 22.58)
 p Value¶0.0030.0070.0020.007
≥1 of genes
 UnMe/local (1 and 2)*516 (11.8)1.00 (referent)1.00 (referent)242 (8.3)1.00 (referent)1.00 (referent)
 UnMe/advanced (3 and 4)†4721 (44.7)6.06 (2.17 to 16.93)5.15 (1.77 to 14.99)2010 (50.0)11.00 (2.03 to 59.75)7.51 (1.31 to 43.24)
 Me/local (1 and 2)‡192 (10.5)0.88 (0.16 to 4.80)0.77 (0.14 to 4.32)466 (13.0)1.65 (0.31 to 8.88)1.50 (0.27 to 8.23)
 Me/advanced (3 and 4)§1512 (80.0)30.00 (6.53 to 137.88)20.35 (4.16 to 99.57)4223 (54.8)13.32 (2.77 to 64.00)10.81 (2.15 to 54.26)
 p Value¶<0.001<0.0010.0010.004
  • *UnMe/local (1 and 2): gene promoter region unmethylated with cancer stage 1 or 2.

  • †UnMe/advanced (3 and 4): gene promoter region unmethylated with cancer stage 3 or 4.

  • ‡Me/local (1 and 2): gene promoter region methylated with cancer stage 1 or 2.

  • §Me/advanced (3 and 4): gene promoter region methylated with cancer stage 3 or 4.

  • ¶p for the joint effect interaction.

  • **NA due to limited numbers of cases.

  • CDKN2A, cyclin-dependent kinase inhibitor 2A; MGMT, O-6-methylguanine DNA methyltransferase; MLH1, mutL homolog 1; NA, not available.