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Diabetes y Cancer de Colon
Diabetes y Cancer de Colon
Journal of the National Cancer Institute, Vol. 97, No. 22, November 16, 2005
ARTICLES
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MATERIALS
AND
METHODS
Search Strategy
RESULTS
Study Characteristics
Twenty-one independent studies met the predefined inclusion criteria. Of these 21 studies, six were casecontrol studies
(10,13,19,26,27,33) (Table 1), 11 were cohort studies that used
incidence and/or mortality rate ratios as the measure of relative
risk (9,11,14,20,2224,28,3032) (Table 2), and four were cohort studies that used standardized incidence and/or mortality
ratio as the measure of relative risk (12,21,25,29) (Table 3).
Eleven studies were conducted in the United States, eight in
Europe, one in Australia, and one in Korea. Of the 15 cohort
studies, incident colorectal cancer was the outcome in seven,
mortality from colon, rectal, or colorectal cancer was the outcome in three, and colorectal cancer incidence and mortality
were reported in five. In the primary meta-analysis of diabetes
and colorectal cancer incidence, we included all six case
control studies (10,13,19,26,27,33) and the nine cohort studies
that reported incidence rate ratios (9,11,14,20,22,24,28,30,31).
These 15 studies included a total of 2 593 935 participants. The
three cohort studies (12,21,25) that reported standardized
incidence ratio were analyzed separately. For the meta-analysis
of diabetes and colorectal cancer mortality, we included the
six cohort studies that reported mortality rate ratio
(11,20,23,28,30,32). These six studies enrolled a total of
2 523 580 participants.
Colorectal Cancer Incidence
Individual study results and the overall summary results for
the six casecontrol and nine cohort studies of diabetes and
colorectal cancer incidence are shown in Fig. 1. Eight of these 15
studies found a statistically significant positive association between diabetes and colorectal cancer incidence (range of individual RRs = 1.02 to 2.78; summary RR for all 15 studies = 1.30,
95% CI = 1.20 to 1.40). No heterogeneity among studies was
found (Q = 17.9; Pheterogeneity = .21; I2 = 21.8%). In a sensitivity
analysis in which one study at a time was excluded and the rest
Journal of the National Cancer Institute, Vol. 97, No. 22, November 16, 2005
1286 CRC
(612 CC, 674 RC)
714 CRC
1192 CRC
(825 CC, 350 RC||)
1953 CRC
(1225 CC, 728 RC)
287 CRC
10 447 CRC
(6862 CC, 3585 RC)
Type of diabetes
Age
Age
Controlled variables
*RR = relative risk; CI = confidence interval; RC = rectal cancer; CRC = colorectal cancer; CC = colon cancer; PCC = proximal colon cancer; DCC = distal colon cancer; BMI = body mass index; ref. = reference.
Measure of relative risk is an odds ratio.
CIs were calculated from raw data reported in the article.
RR (and its 95% CI) was derived by pooling the sex- and/or subsite-specific RRs.
||The numbers of colon and rectal cancer cases do not add up to the total number of colorectal cancer cases because of missing information on subsite.
Journal of the National Cancer Institute, Vol. 97, No. 22, November 16, 2005
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(Table continues)
Study population
Table 2. Characteristics of cohort studies of diabetes and colorectal cancer incidence and mortality*
Age
Controlled variables
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Journal of the National Cancer Institute, Vol. 97, No. 22, November 16, 2005
ARTICLES
Whitehall Study
Exposed group: 224 men with plasma glucose levels of
200 mg/100 mL
Comparison group: 17 051 men with plasma glucose
levels of <96 mg/100 mL
Cancer Prevention Study I
Exposed group: 8258 women and 7229 men with
self-reported DM (type 1 and 2)
Comparison group: 502 592 women and 345 620 men
without self-reported DM
Nurses Health Study
Exposed group: 7069 women with self-reported
DM (type 2)
Comparison group: 111 003 women without
self-reported DM
Cancer Prevention Study II
Exposed group: 26 186 women and 26 617 men with
self-reported DM (type 1 and 2)
Comparison group: 586 135 women and 441 305 men
without self-reported DM
European Prospective Investigation into Cancer
Norfolk Study
Exposed group: 72 women and 149 men with
self-reported DM (type 1 and 2)
Comparison group: 5088 women and 4296 men without
self-reported DM
National Health Insurance Corp
Exposed group: 21 056 women and 41 868 men with
fasting serum glucose level of 7.0mmol/L or
self-reported treatment for DM
Comparison group: 447 559 Korean women and 787 902
Korean men without DM
Study population
Age
Controlled variables
*RR = relative risk; CI = confidence interval; CRC = colorectal cancer; CC = colon cancer; RC = rectal cancer; PCC = proximal colon cancer; DCC = distal colon cancer; DM = diabetes mellitus; BMI = body mass
index; HRT, hormone replacement therapy; NA = not available; ref. = reference.
The measure of RR is a rate ratio (hazard ratio) in all studies, except for one study (11) in which the RR is a pooled odds ratio.
The RR (and its 95% CI) was derived by pooling the sex- and/or subsite-specific RRs.
Excluding participants who had diabetes before age 30 years.
||RR estimates are not available for rectal cancer because there were no cases of rectal cancer among men with diabetes.
Table 2 (continued).
Journal of the National Cancer Institute, Vol. 97, No. 22, November 16, 2005
1683
Table 3. Characteristics of cohort studies of diabetes and colorectal cancer based on standardized incidence/mortality ratio*
Authors, year (ref. No.), country
(follow-up period)
Colorectal cancer incidence
Raggozzino et al., 1982 (25),
United States (19451969)
Study population
Exposed group: 1135 DM patients (type 2)
Comparison group: Rochester population
Age, sex
Age
Age
Age, sex
Age
*RR = relative risk; CI = confidence interval; CRC = colorectal cancer; CC = colon cancer; RC = rectal cancer; PCC = proximal colon cancer; DCC = distal colon
cancer; DM = diabetes mellitus; NA = not available; ref. = reference.
The measure of RR is a standardized incidence (or mortality) ratio.
The RR (and its 95% CI) was derived by pooling the sex- and/or subsite-specific RRs.
The P value reported in the article was used to calculate the CI.
were analyzed, we detected a statistically significant positive association between diabetes and colorectal cancer incidence (range
of summary RRs = 1.25 to 1.36; the lower limit of the 95% CI
never crossed 1.0).
We then conducted subgroup meta-analyses by study design,
geographical area, sex, cancer subsite, and duration of follow-up
(Table 4). The association between diabetes and colorectal cancer incidence was somewhat stronger in casecontrol studies
(summary RR = 1.36; 95% CI = 1.23 to 1.50) than in cohort stud-
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Journal of the National Cancer Institute, Vol. 97, No. 22, November 16, 2005
Controlled variables
Table 4. Summary relative risk (RR) estimates and 95% confidence intervals (CIs) for casecontrol and cohort studies of the association between diabetes and
colorectal cancer incidence by study design, geographical area, sex, cancer subsite, and duration of follow-up
Between studies
Subgroup
Pheterogeneity
6
3
3
9
3.60
1.60
1.42
11.22
.61
.45
.49
.19
7
6
1.92
3.70
14
13
7
4
4
7
4
5
statistics, %*
Pheterogeneity
0
0
0
16.1
0.58
3.06
.45
.08
.93
.59
0
0
1.04
.31
12.15
18.60
.52
.10
0
35.5
1.25
.26
1.68
2.73
3.70
6.08
.95
.44
.30
.41
0
0
19
1.3
0.28
0.66
.60
.42||
7.50
1.36
.06
.85
60.0
0
2.44
.12
estimate was similar for colon cancer (RR = 1.43, 95% CI = 1.28
to 1.60) and for rectal cancer (RR = 1.33, 95% CI = 1.14 to 1.54)
(Pheterogeneity = .42). There was also no statistically significant
difference between subsites in the colon (i.e., proximal colon
versus distal colon). Stratifying cohort studies by duration of
follow-up resulted in no evidence of heterogeneity. Finally, the
summary estimate was similar (Pheterogeneity = .73) for studies
(four casecontrol and four cohort) published before 2000 (RR =
1.28, 95% CI = 1.16 to 1.42) and for studies (two casecontrol
and five cohort) published after 2000 (RR = 1.36, 95% CI = 1.17
to 1.58).
Physical activity and body mass index are potentially the
most important known confounders of the positive association
between diabetes and colorectal cancer risk. When we restricted the meta-analysis to studies that controlled for these
variables (10,11,14,20,22,31,33), we found a positive association between diabetes and colorectal cancer (summary RR =
1.34, 95% CI = 1.20 to 1.49), without statistically significant
heterogeneity among studies (Q = 2.05; Pheterogeneity = 0.91).
Three studies reported both age-adjusted and multivariableadjusted relative risks (11,20,31). When we restricted the metaanalysis to those studies, the positive association between
diabetes and colorectal cancer remained (summary RR adjusted for age only = 1.34, 95% CI = 1.12 to 1.60), and the
estimate was identical to estimates that were adjusted for physical activity and body mass index, as well as other potential
confounders (RR = 1.34, 95% CI = 1.18 to 1.53), indicating a
lack of confounding.
A positive association was observed between diabetes and
colorectal cancer incidence in the three cohort studies that
reported standardized incidence ratios (summary RR = 1.22, 95%
CI = 1.07 to 1.40) (Table 3). The test for heterogeneity among
these three studies was not statistically significant (Q = 4.52;
Pheterogeneity = .10; I 2 = 55.8%).
Journal of the National Cancer Institute, Vol. 97, No. 22, November 16, 2005
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Study design
Casecontrol
Population-based
Hospital-based
Cohort studies
Geographical area
United States
Europe
Sex
Women
Men
Cancer subsites
Colon
Proximal colon
Distal colon
Rectum
Duration of follow-up
10 y
>10 y
No. of studies
Between subgroups
I2
DISCUSSION
1686 ARTICLES
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Journal of the National Cancer Institute, Vol. 97, No. 22, November 16, 2005
NOTES
Supported by grants from the Swedish Research Council/Longitudinal Studies
and the Swedish Cancer Foundation.
Manuscript received May 4, 2005; revised September 12, 2005; accepted
September 30, 2005.
Journal of the National Cancer Institute, Vol. 97, No. 22, November 16, 2005
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