Coffee, Tea, and Caffeine Consumption and Incidence of Colon and Rectal Cancer

Coffee, Tea, and Caffeine Consumption and Incidence of
AR
T
I
CL
E

Colon and Rectal Cancer
Karin B. Michels , Walter C. Willett , Charles S. Fuchs ,
Edward Giovannucci
about a decreased risk of colorectal cancer associated with coffee

Background: Frequent coffee consumption has been associ-
consumption ( 1 ) . However, some researchers contend that a link
ated with a reduced risk of colorectal cancer in a number between high consumption of coffee and a low incidence of
of case – control studies. Cohort studies have not revealed colorectal cancer has been ? rmly established ( 2 ) .
such an association but were limited in size. We explored the

A meta-analysis of coffee consumption and colorectal cancer

association between consumption of coffee and tea and the risk revealed that con? icting results have been obtained in case –
incidence of colorectal cancer in two large prospective cohorts control and cohort studies ( 3 ) . The combined results of 12 case –
of women and men. Methods: We used data from the Nurses’ control studies suggested that coffee consumption is associated
Health Study (women) and the Health Professionals’ Follow-
with a reduced risk of colorectal cancer (odds ratio for high ver-
up Study (men). Consumption of coffee and tea and total caf-
sus low consumption = 0.72; 95% con? dence interval [CI] = 0.61
feine intake were assessed and updated in 1980, 1984, 1986, to 0.84). By contrast, the combined results of ? ve prospective
1990, and 1994 among women and in 1986, 1990, and 1994 cohort studies revealed no association between coffee consump-
among men. The incidence of cancer of the colon or rectum tion and colorectal cancer risk, but the number of cases in each
was ascertained through 1998. Hazard ratios were calculated study was small (relative risk = 0.97; 95% CI = 0.73 to 1.29).
using Cox proportional hazards models that adjusted for

The constituents of coffee might have genotoxic, mutagenic, or
potential confounders. All tests of statistical signi? cance were antimutagenic properties, any of which could in? uence colorectal
two-sided. Results: During almost 2 million person-years of cancer risk. For example, caffeine has been reported to inhibit
chemical carcinogenesis and UVB light- induced carcinogenesis in
follow-up, 1438 cases of colorectal cancer were observed. animal models ( 4 – 6 ) . Conversely, caffeine has also been found to
Consumption of caffeinated coffee or tea with caffeine or be mutagenic ( 7 – 9 ) . Coffee consumption has also been speculated

caffeine intake was not associated with the incidence of colon to decrease the risk for colorectal cancer because it increases large
or rectal cancer in either cohort. For both cohorts combined, bowel motility in the rectosigmoid region, which might decrease
the covariate-adjusted hazard ratio for colorectal cancer contact between bowel contents and colon epithelia and thus de-
associated with consumption of each additional cup of caf-
crease mucosal damage ( 10 ) . Coffee may also prevent mucosal
feinated coffee was 0.99 (95% con? dence interval [CI] = 0.96 damage by reducing the excretion of bile acid and sterols into the
to 1.03). However, participants who regularly consumed two bowel ( 11 ) . Furthermore, caffeine has been reported to lower insu-
or more cups of decaffeinated coffee per day had a 52% (95% lin sensitivity ( 12 ) , and hyperinsulinemia has been hypothesized to
CI = 19% to 71%) lower incidence of rectal cancer than those increase risk of colon cancer ( 13 ) . Another caffeinated beverage,
who never consumed decaffeinated coffee (crude incidence black tea, has been suggested to have anticarcinogenic properties
rate of 12 cases of rectal cancer per 100 000 person-years of due to its ? avonoids, which have antioxidative effects ( 14 ) .
follow-up among participants consuming two or more cups
of decaffeinated coffee per day and crude incidence rate of
19 cases of rectal cancer per 100 000 person-years of follow-

Af? liation of authors:
Obstetrics and Gynecology Epidemiology Center,
up among participants who never consumed decaffeinated Brigham and Women’s Hospital, and Harvard Medical School (KBM); Depart-
coffee). Conclusions: Consumption of caffeinated coffee, tea ments of Epidemiology (KBM, WCW, EG) and Nutrition (WCW, EG), Harvard
with caffeine, or caffeine was not associated with incidence of School of Public Health, Boston; Channing Laboratory, Department of Medicine,
Brigham and Women’s Hospital, and Harvard Medical School, Boston (KBM,
colon of rectal cancer, whereas regular consumption of decaf-
WCW, CSF, EG); Department of Adult Oncology, Dana-Farber Cancer Institute,
feinated coffee was associated with a reduced incidence of Boston, MA (CSF).
rectal cancer. [J Natl Cancer Inst 2005;97:282–92]

Correspondence to: Karin B. Michels, ScD, Obstetrics and Gynecology

Epidemiology Center, Brigham and Women’s Hospital, 221 Longwood Ave.,
Boston, MA 02115 (e-mail: kmichels@rics.bwh.harvard.edu ).

Results of epidemiologic studies have not resolved whether

See “ Notes ” following “ References. ”
coffee consumption is related to colorectal cancer risk. A recent DOI: 10.1093/jnci/dji039
report by the World Cancer Research Fund concluded that the Journal of the National Cancer Institute, Vol. 97, No. 4, © Oxford University
available evidence was not suf? cient to draw any ? rm conclusions Press 2005, all rights reserved.
282 ARTICLES
Journal of the National Cancer Institute, Vol. 97, No. 4, February 16, 2005

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Given the widespread consumption of coffee worldwide and for the HPFS). Follow-up rates for the cohorts were calculated as
the high incidence of colorectal cancer in industrialized countries the proportion of the number of person-years actually followed out
and in South America, where coffee consumption is particularly of the total possible number of person-years followed. The follow-
high, any substantial association between the two could have up rates for the populations studied in this analysis were 98.5% for
considerable public health implications. We examined the rela-
the NHS population and 97.0% for HPFS population.
tions between the consumption of caffeinated and decaffeinated
coffee, the consumption of tea with caffeine, and total caffeine Dietary Assessment
intake and the incidences of colon and rectal cancers among par-
ticipants in the Nurses’ Health Study (NHS) and the Health Pro-

Dietary intake data were collected repeatedly from members
fessionals’ Follow-up Study (HPFS). To our knowledge, these of both cohorts with the use of a validated self-administered
are the largest prospective studies considering this issue.
semiquantitative food frequency questionnaire ( 16 , 17 ) . Among
participants in the NHS, diet was assessed in 1980, 1984, 1986,

S UBJECTS AND M ETHODS
1990, and 1994; among participants in the HPFS, diet was

assessed in 1986, 1990, and 1994.
Study Cohorts

In the NHS, the food frequency questionnaire used for the 1980
dietary assessment consisted of 61 food items and included ques-

The NHS was initiated in 1976, when 121 700 female registered tions about consumption of coffee with caffeine (in cups), tea with
nurses aged 30 – 55 years completed a self-administered question-
caffeine (in cups), cola or other caffeinated sodas (in glasses), and
naire that provided information on demographics, lifestyle, and chocolate (in 1-ounce servings). The 1984 food frequency ques-
medical history. The HPFS comprises 51 529 male health profes-
tionnaire was expanded to include a question about the consump-
sionals, including dentists, veterinarians, pharmacists, optome-
tion of decaffeinated coffee (in cups); the unit for sodas was
trists, osteopaths, and podiatrists, who were 40 – 75 years of age at changed to “ glass, bottle, or can ” and the unit for chocolate was
enrollment in 1986. Participants in both cohorts have been fol-
changed to “ bars or pieces. ” The questionnaires used in 1986, 1990,
lowed through mailed self-administered biennial questionnaires and 1994 were similar to the 1984 questionnaire. In the HPFS, the
that have updated information on lifestyle factors and disease.
1986, 1990, and 1994 food frequency questionnaires were similar

The study populations for the present analyses consisted of all to the expanded NHS questionnaires. The expanded questionnaires
women who were free of cancer, Crohn’s disease, and ulcerative used in both cohorts provided nine mutually exclusive response
colitis in 1980 and who had completed the 1980 food frequency possibilities to describe the participant’s frequency of intake of a
questionnaire and reported having a total caloric intake of be-
particular item: never or less than once per month; 1 – 3 times per
tween 500 and 3500 calories per day (N = 87 794 women) and all month; 1 time per week; 2 – 4 times per week; 5 – 6 times per week;
men who were free of cancer in 1986 and who had completed the 1 time per day; 2 – 3 times per day; 4 – 5 times per day; 6 or more
1986 food frequency questionnaire and reported having a total times per day. Participants were asked to report their average intake
caloric intake of between 800 and 4200 calories per day (N = of one cup of the respective beverages or one serving of any food
46 099 men). A greater proportion of HPFS participants than of over the preceding year. We then converted the responses for indi-
NHS participants completed the food frequency questionnaire vidual beverages to an average daily intake for each participant.
(100% versus 96%) because the food frequency questions were

We used information obtained from U.S. Department of Agri-
part of the enrollment questionnaire for HPFS, whereas diet was culture food-composition sources ( 18 ) to calculate caffeine in-
? rst assessed in the NHS 4 years after study initiation.
take. The caffeine contents used for these calculations were 137

This study and the NHS were approved by the Institutional mg caffeine per cup of coffee, 47 mg caffeine per cup of tea, 46
Review Board (IRB) of the Brigham and Women’s Hospital mg caffeine per can or bottle of cola beverage, and 7 mg caffeine
(Boston, MA); the HPFS was approved by the IRB of Harvard per serving of chocolate.
School of Public Health (Boston, MA).

The reproducibility and validity of the food frequency ques-
tionnaire for both women and men have been reported previously
Ascertainment of Cases and Follow-Up
( 16 , 17 ) . The validity of the questionnaires with respect to indi-
vidual food items has been documented by comparing the re-

On each biennial questionnaire, we asked participants in each sponses of 173 women from the NHS and 127 men from the
cohort whether they had been diagnosed during the previous 2 HPFS to two food frequency questionnaires that were adminis-
years with cancer of the colon or rectum. Deaths were reported to tered approximately 12 months apart and multiple 7-day diet re-
us primarily through family members; we also used the National cords obtained during the 1-year interval ( 19 , 20 ) . Correlation
Death Index and the U.S. Postal Service to identify deaths among coef? cients for the average consumption for coffee and tea as
participants who did not respond to a mailed questionnaire. We assessed by the food frequency questionnaires and the diet re-
estimate that more than 98% of deaths were ascertained ( 15 ) .
cords, correcting for within-person weekly variation in diet, were

When a participant (or the next of kin, for decedents) reported a 0.78 and 0.93, respectively, in the NHS ( 19 ) and 0.93 and 0.77,
diagnosis of cancer, we sought permission to obtain the relevant respectively, in the HPFS ( 20 ) .
medical records and pathology reports. Study physicians blinded to
all questionnaire data reviewed the medical records and extracted Statistical Analysis
information from them on the histologic type, anatomic location,
and stage of the cancer. We included only invasive adenocarcinoma

Daily consumption of coffee, tea, and caffeine was calculated
in this analysis; cases of carcinomas in situ were not considered.
from the frequencies that were pre-speci? ed on the food fre-

For this analysis, participants were followed through 1998 (with quency questionnaire. Categories of frequency of coffee and tea
a cutoff date of June 1, 1998, for the NHS and January 31, 1998, consumption were created, and the lowest intake category was
Journal of the National Cancer Institute, Vol. 97, No. 4, February 16, 2005
ARTICLES 283

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Table 1. Age-standardized distribution of covariates during follow-up, by frequency of caffeinated and decaffeinated coffee and tea consumption and caffeine intake *

Caffeinated coffee consumption (cups/day)
Decaffeinated coffee consumption (cups/day)
Covariate
Never
½
1
2 – 3
4 – 5
>5
Never
¼
½
1 – 1.9

? 2


Women
Total no. person-years
240 507
178 813
216 149
545 379
218 771
66 403
327 938
177 942
151 244
132 475
119 285
Age, y
52.4
55.7
55.3
54.9
53.5
51.7
55.2
56.6
57.6
57.4
56.8
Height, cm
164
164
164
164
164
164
164
164
164
164
164

Body mass index, kg/m 2
25.8
25.8
25.5
25.3
25.1
24.9
25.9
25.8
25.8
25.7
25.5
Family history of colorectal
12.9
13.0
13.1
13.2
12.8
12.8
13.6
13.5
13.3
13.9
13.8
cancer,
%
†
Prior sigmoidoscopy, % ‡
40.6
41.4
39.6
37.7
33.8
29.7
36.3
41.1
42.7
43.9
44.7

Pack-years of smoking ? 35 y in
0.8
0.9
0.9
1.1
1.3
1.5
1.3
1.2
1.2
1.3
1.5
the
past
Alcohol consumption, g/day §
3.8
4.5
5.4
7.0
7.0
6.3
6.3
5.6
5.1
5.3
6.0
Physical activity, h/week
3.2
3.2
3.2
3.1
3.0
3.0
2.9
3.1
3.1
3.1
3.1
Premenopausal, %
31.0
31.6
31.6
31.3
30.6
29.1
24.1
24.6
24.5
24.6
23.8
Current postmenopausal
20.8
25.1
22.8
22.2
19.3
14.3
23.5
29.5
30.3
29.2
27.4
hormone use, %

Regular aspirin use ( ? 1 times/
36.5
40.1
40.2
41.5
43.0
38.3
43.4
43.6
43.4
42.8
45.4
wk),
%
Vitamin supplement use, %
43.5
49.8
45.3
43.4
39.1
31.1
42.5
51.4
53.4
54.2
51.2
Total caloric intake, kcal/day
1668
1718
1686
1708
1718
1706
1726
1768
1758
1761
1769
Red meat consumption,
0.25
0.22
0.23
0.25
0.27
0.31
0.23
0.20
0.18
0.20
0.21
servings/day
Caffeinated coffee consumption,
—
—
—
—
—
—
3.4
3.5
3.2
3.1
3.1
cups/day


Men
Total no. person-years
126 850
104 803
81 524
133 469
43 313
10 131
198 099
94 043
79 083
56 535
58 775
Age, y
57.8
59.1
59.1
58.4
56.9
55.5
56.8
57.9
60.0
60.1
59.0
Height, cm
178
178
178
178
179
179
178
178
178
178
178

Body mass index, kg/m 2
25.5
25.7
25.7
25.9
26.2
26.1
25.8
25.6
25.7
25.8
26.0
Family history of colorectal
9.6
10.1
9.8
9.8
9.0
8.7
9.3
10.2
9.9
9.9
10.3
cancer,
%?
Prior sigmoidoscopy, % ‡
53.7
56.4
51.8
52.4
49.6
42.3
48.2
55.2
57.0
58.2
55.8
Pack-years of smoking before
4.0
4.7
5.5
6.4
8.2
9.6
5.1
4.9
5.2
6.0
7.8
age 30 y
Alcohol consumption, g/day §
7.1
9.5
11.1
13.3
13.7
14.7
10.5
10.2
10.1
10.8
12.8
Physical activity, METS/week
31.4
31.6
30.2
30.7
29.3
25.6
29.9
31.9
32.1
31.5
29.6

Regular aspirin use ( ? 2 times/
34.2
38.0
37.4
38.7
37.1
35.8
34.0
37.0
39.4
40.0
39.9
week),
%
Vitamin supplement use, %
51.7
51.2
50.0
47.9
45.9
42.7
47.6
51.3
50.9
51.1
50.6
Total caloric intake, kcal/day
1894
1914
1939
1982
2052
2175
1951
1961
1925
1943
1957
Red meat consumption,
0.14
0.14
0.16
0.17
0.19
0.21
0.17
0.15
0.14
0.15
0.15
servings/day
Caffeinated coffee consumption,
—
—
—
—
—
—
2.79
3.04
2.72
2.69
2.47
cups/day
(Table continues)
chosen as referent group. Caffeine intake was calculated from the data from the 1980 and 1984 questionnaires was used for analy-
responses to questions about consumption of coffee with caf-
ses of colorectal cancers diagnosed from 1984 through 1986; the
feine, tea with caffeine, carbonated beverages with caffeine, and average of the dietary data from the 1980, 1984, and 1986 ques-
chocolate and was used in the analysis as an energy-adjusted re-
tionnaires was used for analyses of colorectal cancers diagnosed
sidual. Residuals were obtained by regressing log-transformed from 1986 through 1990; and so forth. Similarly, for the male
caffeine on log total energy and determining the antilog of the participants, dietary data from the 1986 questionnaire were used
resulting residual value ( 18 ) . The caffeine residual, which retains for analyses of colorectal cancers diagnosed from 1986 through
the units of intake (in milligrams) when the antilog is used, was 1990; the average of the dietary data from the 1986 and 1990
divided into quintiles on the basis of the distributions of caffeine questionnaires was used for analyses of colorectal cancers diag-
intakes among women and among men.
nosed from 1990 through 1994; and the average of the dietary

To represent the long-term consumption patterns for individ-
data from the 1986, 1990, and 1994 questionnaires was used for
ual subjects as accurately as possible and to reduce random analyses of colorectal cancers diagnosed from 1994 through
within-person variation in beverage consumption, we modeled 1998. Consumption of decaffeinated coffee among women was
the incidence of colorectal cancer in relation to the cumulative ? rst assessed in 1984. Therefore, all analyses pertaining to decaf-
average intake of coffee, tea, and caffeine from all dietary ques-
feinated coffee intake in women used data collected in 1984
tionnaires available up to the start of each 2-year follow-up inter-
through 1998.
val ( 21 ) . Thus, for the female participants we used dietary data

We carried out separate analyses for colon and rectal cancers.
from the 1980 questionnaire for analyses of colorectal cancers Cancer incidence rates associated with each category of coffee
diagnosed from 1980 through 1984; the average of the dietary intake were calculated by dividing the number of new cases of
284 ARTICLES
Journal of the National Cancer Institute, Vol. 97, No. 4, February 16, 2005

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Table 1 (continued).

Tea consumption (cups/day)

Caffeine intake (quintiles)
Covariate
Never
¼
½
1

? 2

1

2

3

4

5


Women
Total no. person-years
297 609
380 689
348 019
230 854
207 919
280 355
295 596
301 955
301 041
300 857
Age, y

53.2
55.2
55.3
54.2
52.4
54.1
54.5
54.6
54.3
54.0
Height, cm
164
164
164
164
164
164
164
164
164
164

Body mass index, kg/m 2
25.2
25.5
25.6
25.5
25.4
25.7
25.6
25.4
25.4
25.2
Family history of colorectal
12.7
13.0
13.2
13.3
13.1
13.1
13.4
13.2
13.1
12.5
cancer, % †
Prior sigmoidoscopy, % ‡
35.7
38.2
39.3
38.7
38.3
41.7
40.5
39.5
36.8
32.4

Pack-years of smoking ? 35 y
1.2
1.1
1.0
0.9
1.0
0.8
0.9
1.0
1.1
1.4
in the past
Alcohol consumption,
6.7
6.3
5.6
5.4
4.9
4.1
5.3
6.8
6.7
6.4
g/day
§
Physical activity, h/wk
3.0
3.2
3.2
3.2
3.1
3.2
3.2
3.2
3.1
3.0
Premenopausal, %
30.3
31.6
31.3
31.1
31.0
31.1
31.7
31.7
31.0
29.8
Current postmenopausal
17.6
23.5
24.0
21.6
19.9
22.3
22.6
22.5
21.3
19.9
hormone use, %
Regular aspirin use
37.0
41.4
41.9
41.8
39.6
37.6
40.4
42.3
41.5
40.4
(
? 1 times/wk), %
Vitamin supplement use, %
38.1
45.0
46.7
44.4
40.9
47.7
46.3
44.9
41.3
37.1
Total caloric intake, kcal
1606
1691
1740
1740
1742
1701
1730
1749
1692
1625
Red meat consumption,
0.26
0.23
0.23
0.25
0.28
0.23
0.25
0.26
0.25
0.25
servings/day


Men
Total no. person-years
171 396
145 549
98 404
47 676
33 646
99 129
101 852
101 871
104 148
104 801
Age, y
57.9
58.3
59.4
58.5
57.5
59.3
58.6
58.9
58.1
57.2
Height, cm
178
178
178
178
178
178
178
178
178
178

Body mass index, kg/m 2
25.8
25.7
25.7
25.7
25.9
25.2
25.7
25.8
25.9
26.1
Family history of colorectal
9.1
10.0
10.1
10.1
9.8
9.7
9.9
9.9
9.7
9.5
cancer,
%

?
Prior sigmoidoscopy, %, ‡
47.0
51.7
51.6
49.2
49.1
54.0
55.6
52.9
52.6
50.4

Pack-years of smoking
6.0
5.2
4.9
5.3
6.1
3.8
4.4
5.4
6.1
7.6
before age 30 y
Alcohol consumption,
11.6
10.6
9.5
9.8
9.9
7.5
9.2
10.9
13.4
11.9
g/day
§
Physical activity, METS/wk
29.2
32.3
31.6
30.5
29.2
33.1
31.5
30.7
30.5
28.0

Regular aspirin use ? 2
34.9
37.7
39.3
37.5
37.9
33.7
37.5
38.0
38.6
37.5
times/week,
%
Vitamin supplement use, %
48.8
50.4
50.1
49.9
48.9
52.2
51.4
49.8
49.5
45.4
Total caloric intake, kcal
1887
1956
1970
2001
2052
1922
1984
1990
2047
1784
Red meat consumption,
0.15
0.15
0.15
0.17
0.18
0.14
0.15
0.16
0.17
0.16
servings/day

* Mean values given for covariates unless otherwise indicated. METS = metabolic equivalents; — = not applicable.
† Mother, father, or sibling.
‡ Ever having had a prior sigmoidoscopy
§ Includes nondrinkers.

? Mother or father.
colon or rectal cancer by the number of person-years of follow-
ards model permits the simultaneous adjustment for multiple
up. The number of person-years of follow-up for each participant potential confounders, including time-dependent covariates.
was calculated from the month we receive the completed 1980 Proportionality of hazards was con? rmed by visual examina-
questionnaire (NHS) or the 1986 questionnaire (HPFS) to the tion of associations across intervals of time. Coffee, tea, and
date of diagnosis of colon or rectal cancer, the date of death, or caffeine consumption were used as time-dependent variables
the end of follow-up (June 1, 1998, for the NHS and January 31, and were cumulatively updated every 4 years, as described
1998, for the HPFS), whichever occurred ? rst. Participants who above. Regression models were adjusted for age (in months),
reported that they had been diagnosed with Crohn’s disease, ul-
family history of colorectal cancer (yes/no), history of sigmoid-
cerative colitis, or cancers other than nonmelanoma skin cancer oscopy or colonoscopy (ever/never), height (in centimeters;
were excluded at baseline, and follow-up was censored when continuous variable), body mass index (in kilograms per meter
these diseases were diagnosed during follow-up.
squared; continuous variable), moderate to vigorous physical

We used a Cox proportional hazards model to calculate the activity (women: <1 hour/week, 1 – 1.9 hours/week, 2 – 3.9 hours/
relative hazard of developing colon or rectal cancer associated week, 4 – 6.9 hours/week, ? 7 hours/week; men: quintiles of met-
with coffee, tea, or caffeine intake ( 22 ) . The proportional haz-
abolic equivalents [working metabolic rate/resting metabolic
Journal of the National Cancer Institute, Vol. 97, No. 4, February 16, 2005
ARTICLES 285

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Table 2. Cumulative updated caffeinated coffee consumption and covariate-adjusted hazard ratio of colorectal, colon, and rectal cancers *


HR for 1

additional cup


Frequency of coffee consumption †
of coffee/day
Cancer
Never
0.5 cup/day
1 cup/day
2 – 3 cups/day
4 – 5 cups/day
>5 cups/day

P trend ‡
(95% CI)


Colorectal cancer

HR, women (95% CI) §
1.00 (referent)

1.11

0.99
1.08
0.95
0.94
.52
0.99


(0.86 to 1.43)
(0.77 to 1.27)
(0.88 to 1.34)
(0.73 to 1.23)
(0.63 to 1.40)

(0.95 to 1.04)
HR, men (95%CI) §
1.00 (referent)
1.00
0.98
0.93
1.04
1.09
.99
1.00


(0.77 to 1.28)
(0.75 to 1.28)
(0.73 to 1.19)
(0.74 to 1.48)
(0.55 to 2.17)

(0.94 to 1.06)

HR, pooled (95% CI) §
1.00 (referent)
1.05
0.99
1.02
0.98
0.98
.60
0.99


(0.88 to 1.26)
(0.82 to 1.18)
(0.87 to 1.19)
(0.80 to 1.21)
(0.69 to 1.38)

(0.96 to 1.03)
No. cases
259
243
228
497
164
40

1431
No. person-years of

367 357
283 616
297 672
678 849
262 085
76 534

1 966 113
follow-up


Colon cancer

HR, women (95% CI) §
1.00 (referent)
1.03
0.92
1.02
0.85
0.85
.26
0.98


(0.78 to 1.36)
(0.70 to 1.20)
(0.82 to 1.28)
(0.64 to 1.12)
(0.55 to 1.32)

(0.94 to 1.03)

HR, men (95% CI) §
1.00 (referent)
1.09
1.04
1.01
0.91
1.39
.88
0.99


(0.83 to 1.45)
(0.77 to 1.41)
(0.77 to 1.33)
(0.59 to 1.36)
(0.69 to 2.78)

(0.92 to 1.06)

HR, pooled (95% CI) §
1.00 (referent)
1.06
0.97
1.02
0.86
0.98
.31
0.98


(0.87 to 1.29)
(0.79 to 1.19)
(0.85 to 1.21)
(0.68 to 1.09)
(0.68 to 1.41)

(0.95 to 1.02)
No. of cases
214
200
185
413
123
35

1170

No. person-years of

367 423
283 665
297 738
678 969
262 125
76 542

1 966 462
follow-up


Rectal cancer

HR, women (95% CI) §
1.00 (referent)
1.71
1.58
1.58
1.80

.29
1.05


(0.88 to 3.34)
(0.82 to 3.06)
(0.87 to 2.88)
(0.94 to 3.44)


(0.95 to 1.17)

HR, men (95% CI) §
1.00 (referent)
0.63
0.78
0.65
1.33

.81
1.02


(0.35 to 1.15)
(0.43 to 1.44)
(0.37 to 1.14)
(0.69 to 2.56)


(0.89 to 1.18)

HR, pooled (95% CI) §
1.00 (referent)

?
1.08

?
1.55

.31
1.04



(0.69 to 1.69)

(0.97 to 2.45)


(0.96 to 1.13)
No. of cases
45
43
43
84
45


260
No. person-years of

367 647
283 917
297 968
679 527
338 867


1 967 926
follow-up

* HR = hazard ratio; CI = con? dence interval.

† The highest frequency of consumption category for rectal cancer is ? 4 cups/day.
‡ Wald test for trend; two-sided

§ Adjusted for age, family history of colorectal cancer, history of sigmoidoscopy, height, body mass index, pack-years of smoking, physical activity, aspirin use,
vitamin supplement intake, alcohol consumption, red meat consumption, total caloric intake, and, among women in addition for menopausal status, postmenopausal
hormone use.

? Data were not combined because of statistically signi? cant heterogeneity (at P <.05) in HR estimates from women and men.
rate/week]), regular aspirin use (women: never or <1/week, 1 –
an increase in intake by one serving (e.g., one cup) per day were
6/week, ?
7/week; men: <2/week,
?
2/week), pack-years of obtained by using daily consumption as a continuous variable.
smoking (both sexes: <10 pack-years, ? 10 pack-years; among

Because the two cohorts differed by sex, follow-up time, food
women: pack-years of smoking ? 35 years in the past; among frequency questionnaires, and covariates, we performed separate
men: pack-years of smoking before age 30 years), ever-use of analyses for each cohort and then combined the results by using
vitamin supplement (use of multivitamins or vitamins A, C, or a ? xed-effects model that weighted the two relative risk estimates
E: yes/no), alcohol consumption (none, <10 g/day, 10 – 19.9 g/
by the inverse of the standard error ( 25 ) . Tests of heterogeneity
day, 20 – 29.9 g/day, ? 30 g/day), total caloric intake (kilocalo-
were used to evaluate whether associations differed between
ries; continuous variable), red meat consumption (<1/week, 1/
women and men; results are shown separately whenever statisti-
week, 2 – 4/week, 5 – 6/week, ?
1/day), and (among women) cally signi? cant heterogeneity was observed.
menopausal status (premenopausal, postmenopausal, uncertain
Analyses were strati? ed by current smoking status and by
menopausal status) and postmenopausal hormone use (never,
alcoholic beverage consumption (both of which were time-
current, past). Covariates were assessed repeatedly and updated dependent covariates). All tests of statistical signi? cance were
throughout the analysis.
two-sided.

Total caloric intake was included in the covariate-adjusted
model to control for confounding by total energy intake and to R ESULTS
minimize extraneous variation due to general under- or over-

reporting of intake of food items on the food frequency question-

From 1980 through 1994, participants in the NHS gradually
naire ( 23 ) . Body mass index and height were included in the decreased the amount of caffeinated coffee they consumed and
analytic model to capture the relation between body composition the number of NHS participants who did not drink coffee also
and size and colorectal cancer risk ( 24 ) . Hazard ratios (HRs) for decreased. In 1980, 22.5% of the women did not drink coffee,
286 ARTICLES
Journal of the National Cancer Institute, Vol. 97, No. 4, February 16, 2005

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Table 3. Cumulative updated decaffeinated coffee consumption and covariate-adjusted hazard ratio of colorectal, colon, and rectal cancer *





Frequency of decaffeinated coffee consumption
HR (95% CI) for
1 additional cup
Cancer
Never
¼ cup/ day
½ cup/ day
1 – 1.9 cups/ day

? 2 cups/ day

P trend †
of coffee/day


Colorectal cancer
HR, women (95% CI) ‡
1.00
0.85
0.76
0.76
0.80
.08
0.96

(referent)
(0.68 to 1.07)

(0.60 to 0.98)

(0.58 to 0.98)

(0.61 to 1.04)

(0.89 to 1.04)
HR, men (95% CI) ‡
1.00
0.77
0.63
0.72
0.85
.51
0.96

(referent)
(0.60 to 1.00)

(0.48 to 0.84)

(0.54 to 0.96)

(0.64 to 1.12)

(0.88 to 1.05)
HR, pooled (95% CI) ‡
1.00
0.82
0.70
0.74
0.82
.08
0.96

(referent)

(0.69 to 0.97)

(0.58 to 0.85)

(0.61 to 0.90)

(0.67 to 0.99)

(0.91 to 1.02)
No. of cases
463
212
167
146
150

1138
No. person-years of

526 036
271 985
230 327
189 009
178 059

1 395 416
follow-up
Colon
cancer

HR, women (95% CI) ‡
1.00
1.00
0.85
0.84
0.90
.20
0.98

(referent)
(0.78 to 1.29)

(0.64 to 1.13)

(0.63 to 1.13)

(0.67 to 1.21)

(0.90 to 1.07)
HR, men (95% CI) ‡
1.00
0.79
0.66
0.71
0.94
.84
1.00

(referent)
(0.60 to 1.05)

(0.48 to 0.89)

(0.51 to 0.99)

(0.70 to 1.28)

(0.91 to 1.09)
HR, pooled (95% CI) ‡
1.00
0.90
0.76
0.78
0.92
.43
0.99

(referent)
(0.75 to 1.09)
(0.62 to 0.93)

(0.63 to 0.97)

(0.74 to 1.14)

(0.93 to 1.05)
No. of cases
357
176
136
116
128

913
No. person-years of

526 140
271 972
230 297
189 072
178 089

1 395 570
follow-up


Rectal cancer
HR, women (95% CI) ‡
1.00
0.46
0.52
0.51
0.48
.15
0.88

(referent)
(0.27 to 0.79)

(0.30 to 0.89)

(0.28 to 0.90)

(0.26 to 0.89)

(0.72 to 1.07)
HR, men (95% CI) ‡
1.00
0.48
0.69
0.76
0.50
.22
0.87

(referent)

(0.21 to 1.13)

(0.31 to 1.53)

(0.34 to 1.70)

(0.20 to 1.27)

(0.67 to 1.14)
HR, pooled (95% CI) ‡
1.00
0.46
0.57
0.58
0.48
.06
0.88

(referent)
(0.29 to 0.73)

(0.36 to 0.89)

(0.36 to 0.93)

(0.29 to 0.81)

(0.75 to 1.03)
No. of cases
105
36
31
30
22

224
No. person-years of

526 655
272 237
230 558
189 149
178 286

1 396 885
follow-up

* HR = hazard ratio; CI = con? dence interval.
† Wald test for trend; two-sided.

‡ Adjusted for age, family history of colorectal cancer, history of sigmoidoscopy, height, body mass index, pack-years of smoking, physical activity, aspirin use,
vitamin supplement intake, alcohol consumption, red meat consumption, total caloric intake, consumption of caffeinated coffee, and, among women in addition for
menopausal status, postmenopausal hormone use.
and 25.0% drank four or more cups of caffeinated coffee per day. ated with a lower mean body mass index among women and
In 1994, 13.2% of the women did not drink coffee, and 14.2% with a higher mean body mass index among men. In both cohorts,
drank four or more cups per day. A similar, but weaker, trend to-
higher caffeinated coffee consumption was also associated with
ward decreased coffee consumption was observed among par-
a lower frequency of sigmoidoscopy, a lower use of vitamin sup-
ticipants in the HPFS. In 1986, 29.9% of the men did not drink plements, and higher frequencies of smoking, alcohol consump-
caffeinated coffee, and 10.8% drank four or more cups per day. In tion, aspirin use, and red meat consumption. Higher consumption
1994, 22.3% of the men drank no coffee and 8.8% drank four or of decaffeinated coffee was associated with higher frequencies of
more cups daily. Similar patterns emerged for tea consumption in sigmoidoscopy, vitamin supplement use, and smoking in both
the two cohorts. Accordingly, mean caffeine intake decreased cohorts and with a higher frequency of aspirin use among men. In
from 391 mg/day (standard deviation [SD] = 270 mg/day) in both cohorts, higher tea consumption was associated with lower
1980 to 242 mg/day (SD = 207 mg/day) in 1994 among all alcohol consumption. Patterns for caffeine intake were similar to
women and from 227 mg/day (SD = 227 mg/day) in 1986 to 221 those for caffeinated coffee consumption ( Table 1 ).
mg/day (SD = 221 mg/day) in 1994 among all men.
During 1 479 804 person-years of follow-up among women, &nb