Case Control Study
Copyright ©The Author(s) 2016.
World J Hepatol. Oct 18, 2016; 8(29): 1234-1243
Published online Oct 18, 2016. doi: 10.4254/wjh.v8.i29.1234
Table 1 Relationship between risk factors and hepatocellular carcinoma and liver cirrhosis development
VariablesControls n (%)Cirrhosis n (%)1OR (95%CI)P-valueHCC n (%)OR (95%CI)2P
Age

< 46 anos238 (67)22 (19)10.31 (5.66-18.76)P < 0.0018 (11)16.36 (6.68-40.05)P < 0.001

≥ 46 anos118 (33)94 (81)63 (89)

Genre

Female95 (26.7)30 (25.9)0.96 (0.54-1.72)P = 0.89319 (26.8)0.59 (0.29-1.22)P = 0.154

Male261 (73.3)86 (74.1)52 (73.2)

Alcoholic habit

Not191 (54)54 (46.6))1.55 (0.91-2.63)P = 0.10627 (38)2.01 (1.03-3.89)P = 0.039

Yes165 (46)62 (53.4)44 (62)

Smoking habit

Nonsmokers199 (56)72 (62)0.47 (0.28-0.78)P = 0.00331 (43.7)0.9 (0.48-1.67)P = 0.734

Smokers157 (44)44 (38)40 (56.3)
Table 2 Association of MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G polymorphisms with hepatocellular carcinoma, adjusted for gender, age, smoking and alcohol consumption
ModelGenotipeControln (%)Case n (%)1OR (95%CI)2P-valueGenotipeControln (%)Case n (%)1OR (95%CI)2P-value
MTHFR C677TMTHFR A1298C
CodominantC/C149 (41.9)28 (39.4)1A/A205 (57.6)32 (45.1)1
C/T174 (48.9)36 (50.7)0.93 (0.51-1.68)0.91A/C116 (32.6)24 (33.8)1.29 (0.69-2.42)0.014
T/T33 (9.3)7 (9.9)1.13 (0.41-3.09)C/C35 (9.8)15 (21.1)3.37 (1.52-7.50)
DominantC/C149 (41.9)28 (39.4)1A/A205 (57.6)32 (45.1)1
C/T-T/T207 (58.1)43 (60.6)0.96 (0.54-1.70)0.88A/C-C/C151 (42.4)39 (54.9)1.71 (0.98-2.99)0.06
RecessiveC/C-C/T323 (90.7)64 (90.1)1A/A-A/C321 (90.2)56 (78.9)1
T/T33 (9.3)7 (9.9)1.18 (0.46-3.05)0.73C/C35 (9.8)15 (21.1)3.04 (1.43-6.47)0.0051
OverdominantC/C-T/T182 (51.1)35 (49.3)1A/A-C/C240 (67.4)47 (66.2)1
C/T174 (48.9)36 (50.7)0.91 (0.52-1.59)0.73A/C116 (32.6)24 (33.8)0.99 (0.55-1.78)0.98
Aditive---------1.01 (0.64-1.58)0.97---------1.71 (1.16-2.52)0.007
MTR A2756GMTRR A66G
CodominantA/A263 (73.9)46 (64.8)1A/A105 (29.5)12 (16.9)1
A/G83 (23.3)21 (29.6)1.58 (0.84-2.98)0.13A/G179 (50.3)50 (70.4)3.26 (1.54-6.87)< 0.001
G/G10 (2.8)4 (5.6)3.29 (0.81-13.30)G/G72 (20.2)9 (12.7)1.16 (0.44-3.11)
DominantA/A263 (73.9)46 (64.8)1A/A105 (29.5)12 (16.9)1
A/G-G/G93 (26.1)25 (35.2)1.73 (0.95-3.15)0.078A/G-G/G251 (70.5)59 (83.1)2.55 (1.24-5.25)0.0072
RecessiveA/A-A/G346 (97.2)67 (94.4)1A/A-A/G284 (79.8)62 (87.3)1
G/G10 (2.8)4 (5.6)2.91 (0.73-11.59)0.15G/G72 (20.2)9 (12.7)0.51 (0.23-1.12)0.077
OverdominantA/A-G/G273 (76.7)50 (70.4)1A/A-G/G177 (49.7)21 (29.6)1
A/G83 (23.3)21 (29.6)1.49 (0.80-2.79)0.22A/G179 (50.3)50 (70.4)3.05 (1.66-5.62)< 0.001
Aditive---------1.68 (1.01-2.77)0.047---------1.16 (0.77-1.73)0.48
Table 3 Association of MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G polymorphisms with Liver Cirrhosis, adjusted for gender, age, smoking and alcohol consumption
ModelGenotipeControl n (%)Case n (%)1OR (95%CI)2P-valueGenotipeControl n (%)Case n (%)1OR (95%CI)2P-value
MTHFR C677TMTHFR A1298C
CodominantC/C149 (41.9)48 (41.4)1A/A205 (57.6)57 (49.1)1
C/T174 (48.9)55 (47.4)0.90 (0.56-1.45)0.56A/C116 (32.6)43 (37.1)1.27 (0.78-2.07)0.21
T/T33 (9.3)13 (11.2)1.37 (0.64-2.95)C/C35 (9.8)16 (13.8)1.85 (0.92-3.71)
DominantC/C149 (41.9)48 (41.4)1A/A205 (57.6)57 (49.1)1
C/T-T/T207 (58.1)68 (58.6)0.97 (0.62-1.52)0.89A/C-C/C151 (42.4)59 (50.9)1.40 (0.90-2.18)0.14
RecessiveC/C-C/T323 (90.7)103 (88.8)1A/A-A/C321 (90.2)100 (86.2)1
T/T33 (9.3)13 (11.2)1.45 (0.71-2.99)0.32C/C35 (9.8)16 (13.8)1.68 (0.86-3.29)0.14
OverdominantC/C-T/T182 (51.1)61 (52.6)1A/A-C/C240 (67.4)73 (62.9)1
C/T174 (48.9)55 (47.4)0.85 (0.54-1.33)0.47A/C116 (32.6)43 (37.1)1.14 (0.72-1.82)0.58
Aditive---------1.07 (0.75-1.51)0.72---------1.33 (0.97-1.83)0.079
MTR A2756GMTRR A66G
CodominantA/A263 (73.9)79 (68.1)1A/A105 (29.5)37 (31.9)1
A/G83 (23.3)32 (27.6)1.52 (0.91-2.53)0.13A/G179 (50.3)55 (47.4)0.94 (0.56-1.56)0.95
G/G10 (2.8)05 (4.3)2.47 (0.75-8.12)G/G72 (20.2)24 (20.7)0.91 (0.49-1.71)
DominantA/A263 (73.9)79 (68.1)1A/A105 (29.5)37 (31.9)1
A/G-G/G93 (26.1)37 (31.9)1.60 (0.98-2.61)0.06A/G-G/G251 (70.5)79 (68.1)0.93 (0.58-1.50)0.77
RecessiveA/A-A/G346 (97.2)111 (95.7)1A/A-A/G284 (79.8)92 (79.3)1
G/G10 (2.8)5 (4.3)2.19 (0.68-7.09)0.21G/G72 (20.2)24 (20.7)0.95 (0.55-1.64)0.86
OverdominantA/A-G/G273 (76.7)84 (72.4)1A/A-G/G177 (49.7)61 (52.6)1
A/G83 (23.3)32 (27.6)1.46 (0.88-2.41)0.15A/G179 (50.3)55 (47.4)0.97 (0.62-1.52)0.9
Aditive---------1.54 (1.02-2.33)0.042---------0.95 (0.70-1.30)0.77
Table 4 Interaction between MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G polymorphisms and smoking habits or alcohol drinking on the risk of hepatocellular carcinoma
Smoking habits
Alcoholic habit

No smoker
Smoker
2Pinteraction
Non-alcoholic
Alcoholic
2Pinteraction
CaseControl1OR (95%CI)CaseControl1OR (95%CI)CaseControl1OR(95%CI)CaseControl1OR (95%CI)
MTRA2756G
A/A221421.00241211.000.81171371.00291261.000.43
A/G-G/G10571.59 (0.65-3.87)15361.85 (0.81-4.21)11532.29 (0.91-5.72)14401.40 (0.63-3.12)
MTRRA66G
A/A4551.008501.000.73531.009521.000.34
A/G-G/G281443.04 (0.95-9.71)311072.27 (0.90-5.72)251374.16 (1.11-15.55)341141.98 (0.83-4.75)
MTHFRC677T
C/C15851.0013641.000.5514851.0014641.000.75
C/T-T/T171140.80 (0.35-1.81)26931.13 (0.51-2.52)141050.86 (0.36-2.06)291021.04 (0.48-2.22)
MTHFRA1298C
A/A131191.0019851.000.61111131.0021911.000.56
A/C-C/C19802.00 (0.88-4.56)20721.49 (0.69-3.20)17772.10 (0.86-5.10)22751.49 (0.72-3.07)
Table 5 Interaction between MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G polymorphisms and smoking habits or alcohol drinking on the risk of liver cirrhosis
Smoking habitsAlcoholic habit

No smoker
Smoker
2Pinteraction
Non-alcoholic
Alcoholic
2Pinteraction
CaseControl1OR(95%CI)CaseControlOR+(95%CI)CaseControl1OR(95%CI)CaseControl1OR (95%CI)
MTRA2756G
A/A501421.00291211.000.39361371.00431261.000.73
A/G-G/G21571.35 (0.72-2.53)16362.07 (0.97-4.41)17531.46 (0.72-2.97)20401.74 (0.89-3.38)
MTRRA66G
A/A26551.0011501.000.05114531.0023521.000.42
A/G-G/G451440.63 (0.35-1.17)341071.71 (0.77-3.82)391371.17 (0.56-2.45)401140.78 (0.42-1.48)
MTHFRC677T
C/C31851.0017641.000.9624851.0024641.000.76
C/T-T/T401140.96 (0.54-1.71)28930.98 (0.48-2.02)291051.05 (0.54-2.02)391020.91 (0.49-1.69)
MTHFRA1298C
A/A331201.0024851.000.32231131.0034921.000.56
A/C-C/C38791.68 (0.95-3.00)21721.06 (0.53-2.13)30771.83 (0.95-3.54)29741.11 (0.61-2.03)
Table 6 Regression analysis of data from multiple logistic analyzed clinical parameters and polymorphisms in patients with hepatocellular carcinoma tumors divided into stages 0 and tumore in stages A and B, C and D according barcelona clinic liver cancer criteria
VariablesStage 0 e AEstage B, C e DOR (95%CI)1P
Pacientes n (%)Pacientes n (%)
Alpha fetoprotein
> 500 ng/mL22 (84.6)21 (46.7)ReferenceReference
< 500 ng/mL4 (15.4)24 (53.3)2.66 (0.55-12.72)0.22
Hepatitis B virus
Absence25 (96.2)38 (84.4)ReferenceReference
Presence1 (3.85)7 (15.6)4.06 (0.34-48.29)0.27
Hepatitis C virus
Absence12 (46.2)22 (48.9)ReferenceReference
Presence14 (53.8)23 (41.1)1.43 (0.35-5.78)0.61
Steatohepatitis
Absence26 (100)42 (93.3)ReferenceReference
Presence00 (00)3 (6.7)30.99
Diabetes
Absence18 (69.2)32 (71.1)ReferenceReference
Presence8 (30.8)13 (28.9)0.25 (0.03-1.63)0.15
Death
No24 (92.3)17 (37.8)ReferenceReference
Yes2 (7.7)28 (62.2)25.3 (3.67-174.38)0.0012
MTHFR A1298C
AA10 (38.5)22 (48.9)ReferenceReference
AC/CC16 (61.5)23 (51.1)0.93 (0.22-3.86)0.92
MTHFR C677T
CC11 (42.3)17 (37.8)ReferenceReference
CT/TT15 (57.7)28 (62.2)1.65 (0.34-7.97)0.53
MTR A2756G
AA18 (69.2)28 (62.2)ReferenceReference
AG/GG8 (30.8)17 (37.8)0.78 (0.18-3.43)0.75
MTRRA66G
AA4 (15.4)8 (17.8)ReferenceReference
AG/GG22 (84.6)37 (82.2)1.09 (0.16-7.30)0.93