In Europe and most of the industrialised world, colorectal cancer is the third most
common cancer in men after lung and prostate cancer and the second most common in
women after breast cancer (Parkin, 2001). A genetic component of risk is well established
(Cannon-Albright et al, 1988), but diet is widely thought to be the most important
determinant of risk. Two major reports reviewed the association between meat consumption
and colorectal cancer risk and agreed that the findings were inconsistent, but suggestive
of a positive association (World Cancer Research Fund, 1997; COMA, 1998). Evidence
that risk is reduced by a relatively high intake of fruit and vegetables, and/or dietary
fibre, is suggestive but not conclusive (Fuchs et al., 1999; Michels et al., 2000;
Terry et al, 2001; Bingham et al, 2003).
We aimed to examine the relationship of lifestyle and dietary factors with the incidence
of colorectal cancer in a cohort that included a large proportion of vegetarians.
In particular, we sought to examine whether the risk for colorectal cancer is lower
in vegetarians than in meat-eaters, and low in participants who reported consuming
relatively large amounts of fruit or vegetables and other foods high in fibre.
SUBJECTS AND METHODS
The Oxford Vegetarian Study (Appleby et al, 1999) is a prospective investigation of
11 140 vegetarians and nonvegetarians who were recruited in the United Kingdom between
1980 and 1984. Participants were contacted through the Vegetarian Society of the United
Kingdom, publicity in the national and local media, and word of mouth via participants
already recruited. Non-vegetarian participants were recruited by the vegetarian participants,
who were asked to nominate friends and relatives who ate meat, fish, or both.
Upon entry in to the study, participants completed a questionnaire including a simple
food frequency questionnaire. Questions on other lifestyle factors related to health
(smoking, alcohol consumption, and amount of exercise), date of birth, occupation,
height and weight, and medical history (including illnesses related to the risk of
cardiovascular disease and, for women, reproductive history) were also included. The
validity of the questionnaire has been examined for estimating dietary fibre intake,
but not for other nutrients (Gear et al, 1979). Participants were categorised into
tertiles of the distribution of intake of total fat from animal foods (meat, eggs,
milk, and cheese), as well as for dietary fibre derived from cereals, fruit, and vegetables.
Participants were classified as vegetarians (including lacto-ovo-vegetarians and vegans)
or nonvegetarians (meat eaters and people who ate fish but not meat), using their
answers to questions on the consumption of meat, fish, dairy products, and eggs.
Each participant was flagged at the UK National Health Service central register and
participants were followed for information on cancer registration and death. Participants
were included in this analysis if they were aged 16–89 years at entry, had not been
diagnosed with a malignant cancer before recruitment (except for nonmelanoma skin
cancer, ICD9 code 173), and could be classified according to their smoking status
and alcohol consumption. Participants were followed up to 31 December 1999, subject
to censoring at age 90.
Cox's proportional hazards model was used to estimate the association between selected
nutritional and lifestyle factors and the risk of colorectal cancer. All incidence
rate ratios were adjusted for age at recruitment (in 11 categories: <40, 40–44, 85–89
years) and sex. Further adjustments were made for smoking status (in three categories:
never, former, and current smoker) and alcohol consumption (in three categories: non-/occasional
drinker, 1–7 u week−1 and >7 u week−1). The statistical analysis was performed using
the STATA statistical package (StatCorp. 2001).
RESULTS
A total of 10 998 participants were included in the analysis with an average follow-up
of 17 years. There were 95 incident colorectal cancer cases, 39 in vegetarians and
56 in nonvegetarians. Table 1
Table 1
Baseline characteristics of the participants by sex, given as number (percentage)
of participants except where indicated
Characteristic
Men (n=4162)
Women (n=6836)
Total (n=10998)
Median age at entry (years)
34
33
33
Smoking
Never smoker
1816 (43.6)
4103 (60.0)
5919 (53.8)
Former smoker
1317 (31.7)
1618 (23.7)
2935 (26.7)
Current smoker
1029 (24.7)
1115 (16.3)
2144 (19.5)
Alcohol
<1 unit/week
948 (22.8)
2223 (32.5)
3171 (28.8)
1–7 units/week
1194 (28.7)
3101 (45.4)
4295 (39.1)
>7 units/week
2020 (48.5)
1512 (22.1)
3532 (32.1)
Body mass index
a
(kg m
−2
)
<20
594 (14.4)
1781 (26.6)
2375 (22.0)
20–<22.5
1567 (38.1)
2806 (41.9)
4373 (40.4)
22.5–<25
1261 (30.6)
1407 (21.0)
2668 (25.0)
25+
693 (16.8)
706 (10.5)
1399 (13.0)
Median
22.4
21.4
21.7
Diet group
Non–vegetarians
2565 (61.6)
3780 (55.3)
6345 (57.7)
Vegetarians
1597 (38.4)
3056 (44.7)
4653 (42.3)
Median dietary fibre intake
b
(g day
−1
)
Bottom third
17.9
16.5
17.0
Middle third
27.3
24.7
25.7
Top third
39.6
35.0
36.7
Median animal fat intake
c
(g day
−1
)
Bottom third
25.5
23.6
24.8
Middle third
52.4
45.2
47.2
Top third
74.7
67.0
70.6
a
Body mass index is unknown for 183 participants.
b
Dietary fibre intake (Southgate fibre) is unknown for 3052 participants.
c
Animal fat intake is unknown for 1470 participants.
shows the baseline characteristics of the participants. Median age at entry was 34
years for men and 33 for women. In all, 38% of men and 45% of women were vegetarians.
The Standardized Incidence Ratio (SIR) for colorectal cancer compared to the general
population of England and Wales was 0.91 (95% CI: 0.74–1.12). The SIRs for vegetarians
and non-vegetarians were 0.81 (95% CI: 0.58–1.11) and 1.00 (95% CI: 0.76–1.30), respectively.
Table 2
Table 2
Relative risks (95% CI) for colorectal cancer associated with selected dietary and
lifestyle factors
Factor
Category
Casesa
Relative riskb
P
c
Relative riskd
P
c
Sex
Male
37
1.00
1.00
Female
58
0.85 (0.56–1.29)
0.452
1.02 (0.66–1.56)
0.941
Diet group
Non-vegetarians
56
1.00
1.00
Vegetarians
39
0.72 (0.48–1.10)
0.132
0.85 (0.55–1.32)
0.463
Meat
Not eaten
48
1.00
1.00
Eaten less than daily
21
1.35 (0.80–2.27)
1.19 (0.70–2.02)
Eaten daily
24
1.34 (0.81–2.23)
0.209
1.14 (0.67–1.93)
0.581
Fish
Not eaten
40
1.00
1.00
Less than once/week
23
1.41 (0.84–2.37)
1.21 (0.71–2.06)
Once or more/week
32
1.38 (0.86–2.22)
0.168
1.17 (0.71–1.92)
0.530
Eggs
<1 eggs week−1
15
1.00
1.00
1–5 eggs week−1
58
1.32 (0.75–2.33)
1.24 (0.70–2.20)
6+ eggs week−1
21
1.43 (0.73–2.78)
0.301
1.29 (0.66–2.52)
0.428
Milk
<0.5 pints day−1
31
1.00
1.00
0.5 pints day−1
36
0.88 (0.54–1.42)
0.86 (0.53–1.40)
>0.5 pints day−1
26
1.08 (0.64–1.84)
0.809
1.10 (0.65–1.87)
0.779
Cheese
<5 times week−1
41
1.00
1.00
5 to 9 times week−1
42
1.26 (0.82–1.94)
1.26 (0.82–1.94)
10+ times week−1
9
1.02 (0.49–2.10)
0.580
0.98 (0.48–2.03)
0.631
Fresh or dried fruit
<5 times week−1
31
1.00
1.00
5 to 9 times week−1
33
0.58 (0.35–0.95)
0.59 (0.36–0.98)
10+ times week−1
27
0.57 (0.34–0.97)
0.041
0.60 (0.35–1.02)
0.067
Total vegetables
Lowest third
46
1.00
1.00
Middle third
19
0.52 (0.30–0.89)
0.53 (0.31–0.90)
Highest third
30
0.85 (0.53–1.34)
0.357
0.86 (0.54–1.38)
0.415
Brown bread
<15 slices week−1
45
1.00
1.00
15+ slices week−1
44
0.86 (0.56–1.31)
0.482
0.90 (0.59–1.38)
0.638
White bread
<15 slices week−1
43
1.00
1.00
15+ slices week−1
16
2.25 (1.25–4.04)
0.006
2.11 (1.17–3.81)
0.009
Breakfast cereals
Not eaten
25
1.00
1.00
<5 times week−1
15
1.08 (0.57–2.05)
1.12 (0.59–2.13)
5+ times week−1
47
1.14 (0.70–1.85)
0.606
1.24 (0.76–2.03)
0.389
Total dietary fibre
Lowest third
20
1.00
1.00
Middle third
24
1.03 (0.57–1.87)
1.07 (0.59–1.95)
Highest third
19
0.73 (0.39–1.37)
0.300
0.82 (0.43–1.56)
0.424
Total animal fat
Lowest third
23
1.00
1.00
Middle third
33
1.65 (0.97–2.81)
1.55 (0.91–2.66)
Highest third
20
1.16 (0.64–2.13)
0.528
1.07 (0.58–1.97)
0.660
Vitamin supplements
Not used
65
1.00
1.00
Used
26
1.02 (0.65–1.62)
0.925
1.00 (0.63–1.59)
0.993
Smoking
Never smoker
36
1.00
1.00
Former smoker
43
1.95 (1.24–3.07)
1.80 (1.13–2.85)
Current smoker
16
1.88 (1.03–3.44)
0.009
1.70 (0.92–3.15)
0.034
Alcohol
<1 unit week−1
30
1.00
1.00
1–7 units week−1
39
1.69 (1.04–2.74)
1.53 (0.94–2.49)
>7 units week−1
26
1.81 (1.04–3.15)
0.025
1.53 (0.87–2.69)
0.118
Social class
I–II
29
1.00
1.00
III–V
24
1.46 (0.85–2.52)
0.183
1.44 (0.83–2.48)
0.161
Other/unknown
42
0.97 (0.53–1.76)
0.98 (0.54–1.78)
Exercisee
Low
76
1.00
1.00
High
19
0.82 (0.49–1.37)
0.453
0.82 (0.49–1.36)
0.440
Body mass index (kg m−2)
<20
17
1.00
1.00
20−<22.5
23
0.72 (0.38–1.34)
0.69 (0.37–1.29)
22.5−<25
38
1.48 (0.83–2.66)
1.37 (0.76–2.46)
25+
14
0.83 (0.40–1.70)
0.535
0.74 (0.36–1.53)
0.791
a
The total number of cases does not always equal 95 because the level of the factor
may be unknown for some cases.
b
Adjusted for age and sex.
c
P for trend (or heterogeneity between categories for sex and smoking). The test of
linear trend simply ranks the categories 1, 2, 3 etc. and excludes the other or unknown
category for social class.
d
Adjusted for age, sex, alcohol and smoking.
e
High exercise is defined as sport, keep fit, running or cycling at least twice a week.
shows relative risks (RRs) and confidence intervals, nutritional and lifestyle factors,
and colorectal cancer risk, adjusted for age and sex alone and with further adjustment
for smoking and alcohol. Vegetarians showed a moderately but nonsignificantly lower
risk of colorectal cancer compared with the nonvegetarians (RR 0.72, 95% CI: 0.48–1.10),
but this association became weaker after adjusting for smoking and alcohol (RR 0.85,
95% CI: 0.55–1.32). Among the nonvegetarians, there was no evidence of a positive
association with the frequency of meat consumption. Among the other dietary factors,
the only statistically significant associations with risk were for fruit and white
bread consumption. Participants with the highest consumption of fresh or dried fruit
experienced a reduction of colorectal cancer risk (RR 0.57, 95% CI: 0.34–0.97, P for
trend=0.041), although the association was no longer statistically significant after
adjusting for smoking and alcohol. Participants eating 15 or more slices of white
bread per week compared with those eating less than 15 had significantly higher risk
(RR=2.25, 95% CI: 1.25–4.04; P for difference between groups=0.006), which remained
highly significant after adjusting for alcohol and smoking.
After adjusting for alcohol intake, both current and former smokers had an increased
risk of colorectal cancer compared with the never smokers (RR=1.70, 95% CI: 0.92–3.15
and RR=1.80, 95% CI: 1.13–2.85, respectively). Among the other lifestyle factors,
social class, exercise, alcohol consumption, and body mass index were not significantly
associated with the risk of colorectal cancer.
DISCUSSION
This prospective study had a wide variation in diet due to the inclusion of a large
proportion of vegetarians. The main limitation is the relatively small number of colorectal
cancer cases and the lack of sophistication of the food frequency questionnaire.
The present analysis did not find a significant difference in risk between nonvegetarians
and vegetarians. Furthermore, no increase in risk of colorectal cancer was seen with
higher meat consumption among nonvegetarians. Nevertheless, the lack of statistical
association may reflect the relative small number of cases. A previous analysis of
mortality in this cohort (Appleby et al, 2002) showed similar death rates for colorectal
cancer in vegetarians and non-vegetarians based on 25 and 24 deaths from colorectal
cancer, respectively. However, in a prospective investigation of Seventh-day Adventists
(Singh and Fraser, 1998), cancer of the colon was significantly more common in non-vegetarians
than in vegetarians. It could be suggested that the nonvegetarians in our study represent
a healthy group compared with the population at large, and that this might account
for the lack of difference between the vegetarians and non-vegetarians; however, the
SIR among non-vegetarians was exactly one.
Fresh or dried fruit consumption was found to be significantly associated with colorectal
cancer risk, although this association became nonsignificant after adjusting for alcohol
and smoking. An approximately 40% decrease in risk was seen in people eating fresh
or dried fruit five or more times per week compared with persons eating less than
this amount. We did not observe a significant association for brown bread and risk
of colorectal cancer, but a two-fold increase in risk was detected in those consuming
15 or more slices of white bread per week. White bread consumption may be a marker
of an unhealthy diet, although an adverse association of refined carbohydrates with
risk has been noted before (Chatenoud et al, 1999). We did not observe a significant
association between fibre and colorectal cancer risk; however, information needed
to estimate dietary fibre intake was unavailable for 32 cases, and the results are
compatible with a recent report of a reduction in risk with high fibre intake (Bingham
et al, 2003).
Our study suggested that smoking was associated with an almost two-fold increase in
risk of colorectal cancer, although this association was attenuated by adjusting for
alcohol consumption. The apparent adverse effect of alcohol was also partially confounded
by smoking. Both the WCRF report (World Cancer Research Fund, 1997) and a comprehensive
review by Potter (1999) concluded that smoking and alcohol are probable risk factors
for colorectal cancer.