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RESULTS
Selected characteristics of
the study population are presented in Table 1. A total of 362 study
participants (157 cases and 205 controls) were included. On average,
individuals with colorectal adenoma were more likely to be male,
slightly older, and smokers than were controls. Controls were more
likely to have histories of colon cancer in first-degree relatives,
to take NSAIDs, and to consume greater amounts of calcium.
Table 1. Selected characteristics of cases and controls,
Markers of Adenomatous Polyps (MAP) Study, 1994-1997.
|
|
Cases |
Controls |
P-valuea |
|
|
(n = 157) |
(n = 205) |
|
|
|
|
|
|
Demographic factors |
|
|
|
|
|
|
|
|
|
Age (yrs.) (yrs.) (yrs.) |
58 (8.3) |
56 (10.2) |
0.01 |
|
Male (%) |
56 |
34 |
< 0.0001 |
|
White (%) |
87 |
88 |
0.61 |
|
College education (%) |
17 |
23 |
0.13 |
|
|
|
|
|
|
Major risk factors |
|
|
|
|
Family history of colon cancer (%)c |
19 |
35 |
0.001 |
|
Currently smoke cigarettes (%) |
31.2 |
19.3 |
0.01 |
|
NSAIDd use (%) |
46.5 |
54 |
0.15 |
|
|
|
|
|
|
Dietary intakesb |
|
|
|
|
Total energy (kcal/d)kcal/d) |
2,029 (853)9 (853)9 (853)9 (853)9 (853)9 (853)9 (853)9 (853)9 (853)9 (853)9 (853)9 (853) |
2,174 (2,097) |
0.42 |
|
Total fat (g/d) |
73 (41)73 (41)73 (41) |
72
(69) |
0.96 |
|
Total meat (serv/wk) |
4.3 (1.4)3 (1.4)3 (1.4) |
4.4 (1.4) |
0.50 |
|
Total fruits and vegetables (serv/wk) |
6.1 (3.6)1 (3.6)1
(3.6)1 (3.6)1 (3.6)1 (3.6)1 (3.6)1 (3.6)1 (3.6)1 (3.6)1 (3.6)1 (3.6) |
6.6 (4.1) |
0.29 |
|
Total calcium (mg/d) |
726 (415)6 (415)6 (415) |
896 (790) |
0.01 |
|
Total vitamin D (IU/d) |
312 (262)2 (262)2 (262) |
365 (382) |
0.14 |
|
Total folate (mcg/d) |
414 (247)4 (247)4
(247)4 (247)4 (247)4 (247)4 (247)4 (247)4 (247) |
468 (414) |
0.15 |
|
Total alcohol (g/d) |
8.1 (14.5) (14.5) (14.5) (14.5) |
5.2 (21.5) |
0.15 |
a Based on chi square test for
categorical variables and analysis of covariance (ANACOVA) for
continuous variables.
b Age-adjusted means (Standard Deviation) presented
unless otherwise indicated.
c Family history of colon cancer in first-degree
relative.
d Nonsteroidal anti-inflammatory drug.
IL-6 -174G/C polymorphism genotyping analyses revealed equivalent
allele frequencies for cases (G = 64%, C = 36%) and controls (G =
61%, C = 39%). These frequencies were in accordance with other
studies. The genotype distribution for the IL-6 polymorphism in the
population as a whole (p = 0.62), in patients with colorectal
adenoma (p = 0.64), and in controls (p = 0.61) was in agreement with
the Hardy-Weinberg equilibrium.
Age- and sex-adjusted associations of IL-6 genotypes and adenomas
are presented in Table 2. Because of the small sample size, and
since those who were C/G or C/C tended to be at lower risk relative
to those who were G/G, for the remaining analyses, we combined C/G
or C/C individuals (i.e., those who carried at least one C allele).
The odds ratio (OR) for those with at least one C allele vs. those
who were G/G was 0.83 (95% confidence interval [CI] 0.52 - 1.30).
Table 2. Age- and sex-adjusted associations of IL-6 -174G/C
genotypes and risk for incident sporadic colorectal adenomas, MAP
study, 1994-1997.
|
|
Cases (n = 157) |
Controls (n = 205) |
|
|
|
n |
% |
n |
% |
ORa |
(95% CI)b |
|
Genotypes |
|
|
|
|
|
|
|
GG |
65 |
41.4 |
74 |
36.1 |
1.00 |
|
|
GC |
70 |
44.6 |
102 |
49.8 |
0.70 |
(0.47 - 1.22) |
|
CC |
22 |
14.0 |
29 |
14.1 |
0.93 |
(0.47 - 1.86) |
|
GC+CC |
92 |
58.6 |
131 |
63.9 |
0.83 |
(0.52 - 1.30) |
|
(p-trend) |
|
|
|
|
(0.50) |
|
a
Odds ratio.
b Ninety-five percent confidence interval.
Age- and sex-adjusted associations of IL-6 genotypes and
adenomas according to adenoma characteristics are shown in Table 3.
No statistically significant associations were observed although
there appeared to be decreased risk of pedunculated adenomas (OR
0.57, 95% CI 0.29 – 1.08) but not for sessile adenomas (OR 0.98, 96%
CI 0.58 – 1.66) in association with the C allele.
The results of analyses to assess potential genotype-environment
interactions are shown in Table 4. Individuals who had at least one
C allele and were also female (OR 0.50, 95% CI 0.26 – 0.95),
non-smoking (OR 0.32, 95% CI 0.15 – 0.69), and NSAID users (OR 0.43,
95% CI 0.20 – 0.92) were at statistically significantly reduced
risk. Those subjects who had at least one C allele and were at or
below the median age of 57 years appeared to be at decreased risk
(OR 0.62, 95% CI 0.32 – 1.19), as were non-alcohol consumers (OR
0.54, 95% CI 0.25 – 1.17).
Table 3. Multivariable-adjusteda associations of IL-6 -174G/C
genotypes and risk for incident, sporadic colorectal adenomas
according to adenoma characteristics, MAP study, 1994-1997.
|
Adenoma characteristics |
IL-6
-174G/C Genotypes |
|
GG |
|
GC + CC |
|
#Cases/Controls |
ORa |
|
#Cases/Controls |
OR b (95% CI)c |
|
|
|
|
|
|
|
|
Multiplicity |
|
|
|
|
|
|
1 |
42/74 |
1.0 |
|
55/131 |
0.76 (0.45 - 1.26) |
|
>1 |
23/74 |
1.0 |
|
37/131 |
0.97 (0.51 - 1.85) |
|
|
|
|
|
|
|
|
Shape |
|
|
|
|
|
|
Sessile |
39/74 |
1.0 |
|
66/131 |
0.98 (0.58 - 1.66) |
|
Pedunculated |
25/74 |
1.0 |
|
24/131 |
0.57 (0.29 - 1.08) |
|
|
|
|
|
|
|
|
Size (cm)d |
|
|
|
|
|
|
<1.0 |
50/74 |
1.0 |
|
75/131 |
0.86 (0.53 - 1.39) |
|
³
1.0 |
15/74 |
1.0 |
|
17/131 |
0.72 (0.33 - 1.58) |
|
|
|
|
|
|
|
|
Dysplasiae |
|
|
|
|
|
|
Mild |
35/74 |
1.0 |
|
47/131 |
0.78 (0.45 -1.34) |
|
³
Moderate |
30/74 |
1.0 |
|
45/131 |
0.88 (0.50-1.57) |
|
|
|
|
|
|
|
|
Morphologyf |
|
|
|
|
|
|
Tubular |
61/74 |
1.0 |
|
84/131 |
0.80 (0.50 - 1.28) |
|
Any villous |
4/74 |
1.0 |
|
8/74 |
1.26 (0.36 - 4.44) |
|
|
|
|
|
|
|
|
Location |
|
|
|
|
|
|
Colon only |
50/74 |
1.0 |
|
76/131 |
0.81 (0.5 -1.30) |
|
Colon & rectum |
10/74 |
1.0 |
|
16/131 |
0.97 (0.41 - 2.30) |
a Adjusted for age, sex, smoking, family
history of colon cancer in a first-degree relative, and NSAID use in
the polytomous logistic model.
b Odds ratio.
c Ninety-five percent confidence interval.
d Greatest diameter of largest adenoma.
e Dysplasia in adenoma with greatest
degree of dysplasia.
f If multiple adenomas, classified as "Any villous" if
any adenoma villous or tubulovillous.
Table 4.
Multivariable-adjusteda joint and combined
associations of IL-6 -174G/C genotypes and various risk factors for
colorectal neoplasms and risk for incident, sporadic colorectal
adenomas, Markers for Adenomatous Polyps (MAP) Study, 1994-1997.
|
Risk
Factors |
IL-6 -174G/C Genotypes |
|
GG |
|
GC + CC |
|
#Cases/
Controls |
ORb
(95% CI)c |
|
#Cases/
Controls |
ORb
(95% CI)c |
|
Age (yrs.) |
|
|
|
|
|
|
£ 57 |
27/36 |
1.0 |
|
33/65 |
0.62
(0.32-1.19) |
|
> 57 |
38/38 |
1.03
(0.52-2.04) |
|
59/66 |
1.00
(0.54-1.84) |
|
Sex |
|
|
|
|
|
|
Male |
35/27 |
1.0 |
|
57/43 |
0.95
(0.51-1.78) |
|
Female |
30/47 |
0.70
(0.35-1.42) |
|
35/88 |
0.50
(0.26-0.95) |
|
Current
smokers |
|
|
|
|
|
|
No |
21/29 |
1.0 |
|
17/66 |
0.32
(0.15-0.69) |
|
Yes |
44/45 |
0.89
(0.44-1.79) |
|
75/65 |
1.14
(0.60-2.17) |
|
Current
drinkers |
|
|
|
|
|
|
No |
17/26 |
1.0 |
|
22/52 |
0.54
(0.25-1.17) |
|
Yes |
48/48 |
0.85
(0.41-1.76) |
|
70/79 |
0.81
(0.41-1.62) |
|
NSAIDd
use |
|
|
|
|
|
|
No |
50/52 |
1.0 |
|
79/93 |
0.92
(0.56-1.51) |
|
Yes |
15/22 |
0.85
(0.39-1.88) |
|
13/38 |
0.43
(0.20-0.92) |
|
Total
calcium intakee |
|
|
|
|
|
Low |
38/34 |
1.0 |
|
49/59 |
0.68
(0.37-1.26) |
|
High |
27/40 |
0.56
(0.28-1.13) |
|
43/72 |
0.57
(0.31-1.05) |
a Adjusted for age, sex,
total energy intake, history of colon cancer in a first degree
relative, nonsteroidal anti-inflammatory drug use, current smoking
status, and total calcium and alcohol intakes.
b b Odds ratio.
c Ninety-five percent confidence interval.
d Nonsteroidal anti-inflammatory drug.
e Based on sex-specific median calcium
intakes in controls: 733.4 mg/d in men and 746.0 mg/d in women. |
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