Folate Intake, MTHFR Polymorphisms, and the Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis
Table 2
Subgroup analysis for the MTHFR C677T polymorphism.
Number of studies
Number of participants in case/control
Summary effect estimate
95% CI
Tests for heterogeneity
CC genotype
Comparator genotype
Subgroup by sex
Pooled studies for sex
(%)
CT versus CC
11
1,650/1,833
1,420/1,523
1.04
0.94–1.16
χ² = 14.28, df = 10 (P = 0.16)
30
TT versus CC
11
1,650/1,833
326/425
0.87
0.75–1.01
χ² = 14.01, df = 10 (P = 0.17)
29
Men
CT versus CC
9
1,257/1,436§
1,081/1,199§
1.12
0.94–1.34
χ² = 18.68, df = 8 (P = 0.02)
57
TT versus CC
9
1,257/1,436§
271/346§
0.87
0.74–1.02
χ² = 8.36, df = 8 (P = 0.40)
4
Women
CT versus CC
8
755/897§
627/773§
0.98
0.85–1.12
χ² = 7.63, df = 7 (P = 0.37)
8
TT versus CC
8
755/897§
162/217§
0.92
0.65–1.31
χ² = 20.74, df = 7 (P = 0.004)
66
Subgroup by cancer type
Pooled studies
CT versus CC
27
3,735/6,767
3,403/6,307
1.01
0.95–1.08
χ² = 23.65, df = 26 (P = 0.60)
0
TT versus CC
24*
3,735/6,767
886/2,117
0.80
0.71–0.89
χ² = 31.45, df = 23 (P = 0.11)
27
Colon cancer studies
CT versus CC
16
2,096/4,463
1,933/4,090
1.01
0.93–1.10
χ² = 11.23, df = 15 (P = 0.74)
0
TT versus CC
14**
2,096/4,463
452/1,352
0.76
0.64–0.91
χ² = 22.79, df = 13 (P = 0.04)
43
Rectal cancer studies
CT versus CC
11
1,639/3,291
1,470/2,996
1.10
0.92–1.31
χ² = 27.95, df = 10 (P = 0.002)
64
TT versus CC
10
1,639/3,291
386/1,020
0.82
0.72–0.94
χ² = 8.38, df = 9 (P = 0.50)
0
Subgroup by location
Asian countries
CT versus CC
22
2,640/3,401
2,985/3,903
0.98
0.89–1.06
χ² = 23.98, df = 21 (P = 0.29)
12
TT versus CC
20**
2,640/3,401
1,001/1,565
0.83
0.69–1.01
χ² = 49.66, df = 19 (P = 0.0001)
62
European countries
CT versus CC
22
5,480/6,960
5,374/6,857
1.00
0.87–1.13
χ² = 109.92, df = 21 (P < 0.00001)
81
TT versus CC
22
5,480/6,960
1,294/1,793
0.92
0.80–1.06
χ² = 43.74, df = 21 (P = 0.003)
52
USA
CT versus CC
8
2,011/3,355
1,932/2,997
0.98
0.90–1.07
χ² = 6.07, df = 7 (P = 0.53)
0
TT versus CC
8
2,011/3,355
436/1,055
0.73
0.63–0.84
χ² = 1.91, df = 7 (P = 0.96)
0
Middle Eastern countries
CT versus CC
5
277/374
274/302
1.46
0.62–3.46
χ² = 45.30, df = 4 (P < 0.00001)
91
TT versus CC
5
277/374
72/105
0.69
0.42–1.13
χ² = 5.56, df = 4 (P = 0.23)
28
Subgroup by control
Healthy person controls
CT versus CC
45
8,706/12,958
8,043/12,044
1.02
0.94–1.11
χ² = 154.26, df = 44 (P < 0.00001)
71
TT versus CC
43**
8,706/12,958
2,136/3,636
0.90
0.81–1.00
χ² = 88.37, df = 42 (P = 0.0001)
52
Hospital patient controls
CT versus CC
16
2,418/2,863
2,932/3,619
0.93
0.83–1.05
χ² = 27.35, df = 15 (P = 0.03)
45
TT versus CC
16
2,418/2,863
939/1,254
0.82
0.68–1.00
χ² = 36.07, df = 15 (P = 0.002)
58
§Not all studies reported both case and control numbers.
*There were two studies without TT genotype information, one study with rectal cancer data, and two studies with colon cancer data.
**There were two studies that had 0 people for the TT genotype. CRC: colorectal cancer.
