01.12.2017 | Research article | Ausgabe 1/2017 Open Access

Combination of Helicobacter pylori infection and the interleukin 8 –251 T > A polymorphism, but not the mannose-binding lectin 2 codon 54 G > A polymorphism, might be a risk factor of gastric cancer
- Zeitschrift:
- BMC Cancer > Ausgabe 1/2017
Background
Methods
Diagnosis of H. pylori infection
Histologic examination of chronic gastritis
Genotyping of MBL2 exon 1 codons 52, 54 and 57, and of IL-8 -251
Measurement of serum MBL levels
Measurement of IL-8 levels in gastric mucosal tissues
Analysis of global raw data regarding IL-8 -251 T > A polymorphism and GC risk
Statistical analysis
Results
Hp (−)
Control
(
n = 176)
|
Hp (+)
NAG
(
n = 108)
|
Hp (+)
Mild AG
(
n = 52)
|
Hp (+)
Severe AG
(
n = 61)
|
DU
(
n = 175)
|
GC
(
n = 283)
|
p
|
|
---|---|---|---|---|---|---|---|
Sex (M:F)
|
87:89
|
41:67
|
23:29
|
37:24
|
90:85
|
151:132
|
0.1832
a
|
Mean age (years)
|
52.5 ± 6.7
|
51.58 ± 6.65
|
59.52 ± 8.30
|
60.89 ± 8.55
|
53.2 ± 12.6
|
55.5 ± 8.8
|
0.1431
b
|
Alcohol consumption (%)
|
52.27%
|
51.85%
|
48.46%
|
47.54%
|
57.71%
|
55.48%
|
0.1751
a
|
Smoking habits (%)
|
19.89%
|
18.52%
|
30.77%
|
26.23%
|
58.86%
|
40.99%
|
<0.0001
a
|
High salt intake (%)
|
25.00%
|
26.85%
|
16.92%
|
49.18
|
39.43%
|
48.41%
|
<0.0001
a
|
FHx of GC (%)
|
10.23%
|
15.52%
|
13.79%
|
16.39%
|
10.86%
|
20.85%
|
0.0043
a
|
Hp positivity (%)
|
0%
|
100%
|
100%
|
100%
|
96.00%
|
73.14%
|
<0.0001
a
|
The frequencies of MBL2 codon 54 and IL-8 -251 genotypes in the control and disease groups
Genotype
|
Control
n = 176 (%)
|
Hp (+)
NAG
n = 108 (%)
|
Hp (+)
Mild AG
n = 52 (%)
|
Hp (+)
Severe AG
n = 61 (%)
|
Hp (−)
DU
n = 7 (%)
|
Hp (+)
DU
n = 168 (%)
|
Hp (−)
GC
n = 76 (%)
|
Hp (+)
GC
n = 207 (%)
|
|
---|---|---|---|---|---|---|---|---|---|
MBL2 codon 54
|
G/G (wild type)
|
103 (58.52)
|
65 (60.19)
|
29 (55.77)
|
32 (52.46)
|
4 (57.14)
|
95 (56.55)
|
41 (53.95)
|
129 (62.32)
|
G/A(heterozygote)
|
63 (35.80)
|
37 (34.26)
|
22 (43.31)
|
27 (44.26)
|
3 (42.86)
|
69 (41.07)
|
29 (32.37)
|
67 (32.37)
|
|
A/A (mutant)
|
10 (5.68)
|
6 (5.56)
|
1 (1.92)
|
2 (3.28)
|
0 (0.00)
|
4 (2.38)
|
6 (5.31)
|
11 (5.31)
|
|
G/A + A/A (A carrier)
|
73 (41.48)
|
43 (39.81)
|
23 (44.23)
|
29 (47.54)
|
4 (57.14)
|
73 (43.45)
|
35 (46.05)
|
78 (37.68)
|
|
IL-8 -251
|
T/T (wild type)
|
70 (39.77)
|
52 (48.15)
|
20 (38.46)
|
15 (24.59)
|
3 (42.86)
|
81 (48.21)
|
23 (30.26)
|
58 (28.02)
|
T/A (heterozygote)
|
89 (50.57)
|
49 (45.37)
|
27 (51.92)
|
37 (60.66)
|
3 (42.86)
|
73 (43.45)
|
46 (60.53)
|
122 (58.94)
|
|
A/A (mutant)
|
17 (9.66)
|
7 (6,48)
|
5 (9.62)
|
9 (16.75)
|
1 (14.29)
|
14 (8.33)
|
7 (9.21)
|
27 (13.04)
|
|
T/A + A/A (A carrier)
|
106 (60.23)
|
56 (51.85)
|
32 (61.54)
|
46 (75.41)
|
4 (57.14)
|
87 (51.79)
|
53 (69.74)
|
149 (71.99)
|
Association between MBL2 codon 54 G > A polymorphism and the risk of gastroduodenal diseases
Genotype
|
Disease group
|
Unadjusted OR (95% CI) by univariate analysis
|
p
|
Adjusted OR (95% CI) by multivariate analysis
|
p
|
---|---|---|---|---|---|
G/A (heterozygote)
|
Hp(+) NAG (
n = 49)
|
0.93 (0.56–1.55)
|
0.7828
|
1.02 (0.59–1.75)
|
0.9466
|
Hp(+) mild AG (
n = 27)
|
1.24 (0.66–2.34)
|
0.5074
|
1.16 (0.60–2.26)
|
0.6527
|
|
Hp(+) severe AG (
n = 37)
|
1.38 (0.76–2.52)
|
0.2937
|
1.16 (0.61–2.18)
|
0.6498
|
|
Hp(−) DU(
n = 3)
|
1.23 (0.27–5.66)
|
0.7938
|
1.21 (0.26–5.71)
|
0.8082
|
|
Hp(+) DU (
n = 73)
|
1.19 (0.76–1.85)
|
0.4450
|
1.24 (0.78–1.99)
|
0.3605
|
|
Hp(−) GC(
n = 46)
|
1.16 (0.65–2.04)
|
0.6170
|
1.11 (0.61–2.00)
|
0.7356
|
|
Hp(+) GC (
n = 122)
|
0.85 (0.55–1.31)
|
0.4566
|
0.85 (0.54–1.34)
|
0.7356
|
|
A/A (mutant)
|
Hp(+) NAG (
n = 7)
|
0.95 (0.33–2.74)
|
0.9255
|
1.19 (0.39–3.61)
|
0.7561
|
Hp(+) mild AG (
n = 5)
|
0.36 (0.04–2.89)
|
0.3332
|
0.33 (0.04–2.81)
|
0.3126
|
|
Hp(+) severe AG (
n = 9)
|
0.64 (0.13–3.09)
|
0.5822
|
0.61 (0.12–3.12)
|
0.5560
|
|
Hp(−) DU (
n = 1)
|
1.25(0.32–5.88)
|
0.9521
|
1.24(0.31–5.77)
|
0.9434
|
|
Hp(+) DU (
n = 14)
|
0.43 (0.13–1.43)
|
0.1697
|
0.45 (0.13–1.55)
|
0.2031
|
|
Hp(−) GC (
n = 7)
|
1.51 (0.52–4.42)
|
0.4543
|
1.93 (0.63–5.89)
|
0.2484
|
|
Hp(+) GC (
n = 27)
|
0.88 (0.36–2.15)
|
0.7762
|
1.10 (0.43–2.79)
|
0.8496
|
|
G/A + A/A (A carrier)
|
Hp(+) NAG (n = 56)
|
0.93 (0.57–1.52)
|
0.7820
|
1.04 (0.62–1.75)
|
0.8774
|
Hp(+) mild AG (
n = 32)
|
1.12 (0.60–2.09)
|
0.7239
|
1.05 (0.55–2.00)
|
0.8893
|
|
Hp(+) severe AG (
n = 46)
|
1.28 (0.71–2.29)
|
0.4103
|
1.09 (0.59–2.01)
|
0.7929
|
|
Hp(−) DU (
n = 4)
|
1.06 (0.23–4.87)
|
0.9421
|
1.06 (0.23–4.98)
|
0.9386
|
|
Hp(+) DU (
n = 87)
|
1.08 (0.71–1.66)
|
0.7110
|
1.13 (0.72–1.78)
|
0.5868
|
|
Hp(−) GC (
n = 53)
|
1.20 (0.70–2.07)
|
0.5008
|
1.19 (0.68–2.09)
|
0.5480
|
|
Hp(+) GC (
n = 149)
|
0.85 (0.57–1.29)
|
0.4488
|
0.88 (0.57–1.35)
|
0.5528
|
Serum MBL levels
Association between IL-8 -251 T > A polymorphism and the risk of disease development
Genotype
|
Disease group
|
Unadjusted OR (95% CI) by univariate analysis
|
p
|
Adjusted OR (95% CI) by multivariate analysis
|
p
|
---|---|---|---|---|---|
T/A (heterozygote)
|
Hp(+) NAG (
n = 49)
|
0.74 (0.45–1.22)
|
0.2406
|
0.76 (0.46–1.29)
|
0.3018
|
Hp(+) mild AG (
n = 27)
|
1.06 (0.55–2.05)
|
0.8581
|
1.09 (0.55–2.16)
|
0.8052
|
|
Hp(+) severe AG (
n = 37)
|
1.94 (0.99–3.82)
|
0.0549
|
2.06 (1.01–4.21)
|
0.0471
|
|
Hp(−) DU(
n = 3)
|
0.79 (0.15–4.02)
|
0.7729
|
0.84 (0.16–4.36)
|
0.8342
|
|
Hp(+) DU (
n = 73)
|
0.71 (0.45–1.11)
|
0.1297
|
0.80 (0.50–1.29)
|
0.3616
|
|
Hp(−) GC(
n = 46)
|
1.57 (0.87–2.84)
|
0.1326
|
1.66 (0.89–3.07)
|
0.1058
|
|
Hp(+) GC (
n = 122)
|
1.65 (1.06–2.58)
|
0.0257
|
1.71 (1.07–2.72)
|
0.0252
|
|
A/A (mutant)
|
Hp(+) NAG (
n = 7)
|
0.55 (0.21–1.43)
|
0.2237
|
0.59 (0.21–1.59)
|
0.2952
|
Hp(+) mild AG (
n = 5)
|
1.03 (0.34–3.14)
|
0.9593
|
1.00 (0.31–3.17)
|
0.9941
|
|
Hp(+) severe AG (
n = 9)
|
2.47 (0.93–6.59)
|
0.0710
|
2.42 (0.85–6.84)
|
0.0966
|
|
Hp(−) DU (
n = 1)
|
1.37 (0.13–14.03)
|
0.7895
|
1.66 (0.16–17.71)
|
0.6743
|
|
Hp(+) DU (
n = 14)
|
0.71 (0.33–1.55)
|
0.3905
|
0.72 (0.32–1.63)
|
0.4289
|
|
Hp(−) GC (
n = 7)
|
1.25 (0.46–3.40)
|
0.6577
|
1.19 (0.43–3.34)
|
0.7403
|
|
Hp(+) GC (
n = 27)
|
1.92 (0.95–3.86)
|
0.0683
|
1.94 (0.93–4.06)
|
0.0744
|
|
T/A + A/A
(A carrier)
|
Hp(+) NAG (
n = 56)
|
0.71 (0.44–1.15)
|
0.1669
|
0.73 (0.44–1.22)
|
0.2282
|
Hp(+) mild AG (
n = 32)
|
1.06 (0.56–1.99)
|
0.8651
|
1.07 (0.55–2.08)
|
0.8336
|
|
Hp(+) severe AG (
n = 46)
|
2.03 (1.05–3.90)
|
0.0351
|
2.12 (1.06–4.25)
|
0.0335
|
|
Hp(−) DU (
n = 4)
|
0.88 (0.19–4.05)
|
0.8703
|
0.96 (0.20–4.48)
|
0.3066
|
|
Hp(+) DU (
n = 87)
|
0.71 (0.46–1.09)
|
0.1152
|
0.79 (0.50–1.24)
|
0.3035
|
|
Hp(−) GC (
n = 53)
|
1.52 (0.86–2.70)
|
0.1524
|
1.58 (0.87–2.87)
|
0.1346
|
|
Hp(+) GC (
n = 149)
|
1.70 (1.11–2.60)
|
0.0155
|
1.74 (1.11–2.74)
|
0.0161
|
Comparison of IL-8 levels according to disease phenotypes and IL-8 -251 each genotype
Analysis of global results of IL-8 -251 T > A polymorphism and GC risk
Ethnicity
|
TT / total GC (%)
TT / total controls (%)
OR [95% CI]
|
TA / total GC (%)
TA / total controls (%)
OR [95% CI]
|
AA / total GC (%)
AA / total controls (%)
OR [95% CI]
|
A* / total GC (%)
A* / total controls (%)
OR [95% CI]
|
---|---|---|---|---|
This study
(Korean)
|
81/283 (28.62%)
70/176 (39.77%)
0.60 [0.40, 0.90]
|
168/283(59.36%)
89/176 (50.57%)
1.43 [0.98, 2.09]
|
34/283(12.01%)
17/176(9.66%)
1.27 [0.70, 2.31]
|
202/283(71.38%)
106/176 (60.23%)
1.66 [1.11, 2.47]
|
Korean
|
180/487(36.96%)
244/528(46.21%)
0.68 [0.53, 0.88]
|
241/487(49.49%)
234/528(44.32%)
1.23 [0.96, 1.57]
|
66/487(13.55%)
50/528(9.47%)
1.50 [1.02, 2.20]
|
307/487(63.04%)
284/528 (53.79%)
1.46 [1.14, 1.88]
|
Japanese
|
337/789(42.71%)
485/964(50.31%)
0.74 [0.61, 0.89]
|
375/789(47.53%)
397/964(41.18%)
1.29 [1.07, 1.56]
|
77/789(9.76%)
82/964(8.51%)
1.16 [0.84, 1.62]
|
452/789(57.29%)
479/964(49.69%)
1.36 [1.12, 1.64]
|
Chinese
|
329/926(35.53%)
270/814(33.17%)
1.11 [0.91, 1.35]
|
425/926(45.90%)
406/814(49.88%)
0.85 [0.71, 1.03]
|
172/926(18.57%)
138/814(16.95%)
1.12 [0.87, 1.43]
|
597/926(64.47%)
544/814(66.83%)
0.90 [0.74, 1.10]
|
Caucasian
|
224/732(30.60%)
381/1328(28.69%)
1.10 [0.90, 1.34]
|
365/732(49.86%)
669/1328(50.38%)
0.98 [0.82, 1.17]
|
143/732(19.54%)
278/1328(20.93%)
0.92 [0.73, 1.15]
|
508/732(69.40%)
947/1328(71.31%)
0.91 [0.75, 1.11]
|
Combined
Korean and Japanese
|
598/1559(38.36%)
799/1668(47.90%)
0.70 [0.61, 0.81]
|
784/1559(50.29%)
720/1668(43.17%)
1.29 [1.12, 1.48]
|
177/1559(11.35%)
149/1668(8.93%)
1.29 [1.02, 1.62]
|
961/1559(61.64%)
869/1668(52.10%)
1.42 [1.24, 1.64]
|