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. 2015 Mar 27;10(3):e0123396. doi: 10.1371/journal.pone.0123396

Table 2. Risk of CRC recurrence during follow-up in relation to methylation status in patients with colorectal cancer after surgery.

Recurrence in different stages by methylation Normal tissues Tumor tissues
No. of subjects Incidence rate Crude Adjusted No. of subjects Incidence rate Crude Adjusted
HR 95% CI HR 95% CI HR 95% CI HR 95% CI
p16
    UnMe/local (1&2) a 74 (1767) 4.53 1.00 (Referent) 1.00 (Referent) 51 (1358) 4.42 1.00 (Referent) 1.00 (Referent)
    UnMe/advanced (3&4) b 78 (1941) 23.70 5.08 (2.40–10.77) 6.07 (2.35–15.70) 46 (1180) 21.19 4.69 (1.89–11.65) 6.63 (1.97–22.38)
    Me/local (1&2) c 34 (1032) 3.88 0.70 (0.18–2.62) 0.98 (0.23–4.17) 57 (1442) 4.16 0.87 (0.28–2.70) 1.15 (0.27–4.94)
    Me/advanced (3&4) d 29 (621) 43.48 9.92 (4.47–21.99) 10.85 (4.06–28.96) 61 (1383) 34.71 8.01 (3.34–19.16) 9.64 (2.92–31.81)
MLH1
    UnMe/local (1&2) a 92 (2411) 4.98 1.00 (Referent) 1.00 (Referent) 86 (2148) 5.12 1.00 (Referent) 1.00 (Referent)
    UnMe/advanced (3&4) b 85 (2098) 25.74 5.28 (2.76–10.11) 5.79 (2.67–12.57) 80 (1960) 26.53 5.37 (2.73–10.57) 6.08 (2.66–13.89)
    Me/local (1&2) c 16 (389) NA e NA e NA e NA e NA e 22 (652) 1.53 0.30 (0.04–2.32) 0.48 (0.06–3.90)
    Me/advanced (3&4) d 22 (465) 40.86 8.71 (4.12–18.41) 9.04 (3.79–21.54) 27 (603) 34.83 6.67 (3.14–14.17) 8.29 (3.40–20.22)
MGMT
    UnMe/local (1&2) a 97 (2625) 4.19 1.00 (Referent) 1.00 (Referent) 52 (1424) 3.51 1.00 (Referent) 1.00 (Referent)
    UnMe/advanced (3&4) b 87 (2154) 26.00 6.50 (3.32–12.74) 7.63 (3.34–17.47) 44 (1166) 24.87 6.61 (2.52–17.37) 7.61 (2.23–25.91)
    Me/local (1&2) c 11 (176) 5.68 1.93 (0.24–15.17) 3.04 (0.37–25.05) 56 (1376) 5.09 1.32 (0.42–4.15) 1.48 (0.35–6.25)
    Me/advanced (3&4) d 20 (408) 41.67 11.71 (5.32–25.76) 12.61 (4.90–32.44) 63 (1396) 31.52 9.41 (3.66–24.17) 11.83 (3.49–40.12)

HR, hazard ratio; CI, confidence interval; N/A, not available.

Adjusted for gender, age at surgery (continuous), and adjuvant chemotherapy.

a UnMe/loccal (1&2): gene promoter region unmethylation in cancer stage 1 or 2.

b UnMe/advanced (3&4): DNA promoter region unmethylation in cancer stage 3 or 4.

c Me/local (1&2): DNA promoter region methylation in cancer stage 1 or 2.

d Me/advanced (3&4): DNA promoter region methylation in cancer stage 3 or 4.

e Not available due to limited numbers of cases.