Cancer Causes Control (2010) 21:1513–1521 DOI 10.1007/s10552-010-9580-z
ORIGINAL PAPER
Pickled meat consumption and colorectal cancer (CRC): a case–control study in Newfoundland and Labrador, Canada Josh Squires • Barbara Roebothan • Sharon Buehler • Zhuoyu Sun Michelle Cotterchio • Ban Younghusband • Elizabeth Dicks • John R. Mclaughlin • Patrick S. Parfrey • Peizhong Peter Wang
•
Received: 5 August 2009 / Accepted: 6 May 2010 / Published online: 27 May 2010 Ó Springer Science+Business Media B.V. 2010
Abstract Objective Although a large body of epidemiological research suggests that red meat intake increases the risk of colorectal cancer, little is known regarding how such an association varies across populations and types of red meat. The objective of this study was to assess whether an association exists between the intakes of total red meat and pickled red meat and the risk of colorectal cancer in study subjects residing in Newfoundland and Labrador. Methods This case–control study of 1,204 residents of Newfoundland and Labrador was part of a larger study on colorectal cancer. Personal history food frequency questionnaires were used to collect retrospective data from 518 individuals diagnosed with colorectal cancer and 686 controls. Intakes were ranked and divided into tertiles.
J. Squires B. Roebothan S. Buehler Z. Sun P. P. Wang (&) Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL 1B 3V6, Canada e-mail:
[email protected] M. Cotterchio Population Studies and Surveillance, Cancer Care Ontario, Toronto, ON, Canada J. R. Mclaughlin Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada B. Younghusband E. Dicks P. S. Parfrey Clinical Epidemiology Unit, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada P. P. Wang School of Public Health, Tianjin Medical University, Tianjin, China
Logistic regression was used to examine the possible association between meat intakes and colorectal cancer diagnosis while controlling for possible confounding factors. Results A positive, but non-statistically significant, association between total red meat intake and CRC was observed in this study. Pickled red meat consumption was found to be significantly associated with an increased risk of CRC (men, OR = 2.07, 95% CI 1.37–3.15; women, OR = 2.51, 95% CI 1.45–4.32), the odds ratios increasing with each tertile of consumption, suggesting a dose– response effect. Conclusion Intake of pickled red meat appears to increase the risk of colorectal cancer in Newfoundland and Labrador. Keywords Colorectal cancer Red meat Pickled meat Newfoundland & Labrador Case–control
Introduction Colorectal cancer (CRC) has become a health problem of increasing significance in Canada, with an estimated 21,500 new cases, and 8,900 deaths in 2008 [1]. CRC is the third most common type of cancer in Canadian men and women [1]. In Canadian men, it is estimated that in 2008 the number of cancer-related deaths attributed to CRC (12.4%) will be exceeded only by lung cancer (28.4%). In women, a similar outcome is expected with the number of cancer-related deaths due to CRC (11.6%) being exceeded only by lung cancer (26.3%) and breast cancer (15.2%) [1]. Newfoundland and Labrador (NL), according to the Canadian Cancer Society, have the highest age-standardized incidence rate of CRC in Canada at 86 per 100,000
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[1]. The national average, including all provinces and territories, is 62 per 100,000. Epidemiological research to date has suggested that a wide range of environmental and life style factors may contribute to the increased incidence of CRC such as smoking, alcohol intake, ionizing radiation, and lack of physical activity; however, the results have been inconsistent [2–5]. It is generally believed that dietary habits are a major contributor to CRC and are at least responsible for 30% of CRC cases [6], yet epidemiological efforts linking individual foods and nutrients to CRC in the past three decades have produced little convincing evidence. According to the recent systematic literature review conducted by the World Cancer Research Foundation, only red meat, processed meat, and alcohol drinking in men were classified as risk factors of CRC with convincing evidence [7–9]. However, little is known about how the effects of red meat intake on CRC vary across populations, and the association between pickled meat and CRC has not been adequately examined. Despite the high incidence rates of CRC in Canada, epidemiological studies assessing dietary factors and colorectal cancer were limited, and the few available studies were largely based on select populations [10–12]. Using the data collected from a large population-based case–control study in Ontario, Cotterchio [13] first reported that red meat intake was significantly associated with an increased risk of CRC in Canada, but this association has not been assessed in the Newfoundland population. It has been suggested that reducing the quantity of meat in a person’s diet could significantly reduce the risk of developing CRC [14, 15]. The province of Newfoundland and Labrador (NL) is located farthest east in North America and consists of the island of Newfoundland, and Labrador on the Canadian mainland. Compared with the rest of Canada, NL is geographically isolated and has a homogeneous population of which an estimated 98% are of English or Irish descent. According to the 2001 Statistics Canada report, the population in NL is about 510,000 with over 40% of the residents living in rural communities [16]. Due to distinct geography and heritage, NL is known for its traditional foods and one such is the pickled meat [17]. Pickled meat refers to salted and pickled meats such as trimmed navel beef and cured pork riblets. It is often made by curing pieces of beef navel or pork riblets in a mixture of water, salt, sodium erythorbate, and sodium nitrate. In NL, pickled meat can be either homemade or purchased from farmers markets or supermarkets. While little has been written about the distinct dietary characteristics of Newfoundlanders and Labradoreans, given the frequency and quantity of picked meat consumption, NL is probably matched by no other populations in the world. This not
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only makes the population of NL ideal for the study of the association between pickled meat and colorectal cancer [18], such a study also has public health implications in terms of identifying important modifiable risk factors of CRC in this population [7, 9]. The objective of this study was to establish whether an association exists between meat consumption and CRC in a sample of adults residing in NL, focusing primarily on pickled meat intake. If an association was detected, the size of the association would be assessed.
Methods Study population This study utilized data that had already been collected from an existing population-based case–control study of more than 4,000 participants from NL and ON. Cases were recruited using the provincial cancer registry, resulting in the creation of the Newfoundland and Labrador Colorectal Cancer Registry (NFCCR). Cases were identified using the provincial cancer registry records, which were then verified using pathology reports. Persons diagnosed with colorectal cancer between 1999 and 2003 were eligible for inclusion in the study. Controls belonged to a random sample of the NL population aged 20–74, recruited using random digit dialing [19, 20]. Information including personal history, life style, and dietary characteristics was collected using a Personal History Questionnaire (PHQ) and Food Frequency Questionnaire (FFQ), with these questionnaires being developed for and utilized in the larger study. The PHQ and FFQ were self-administered surveys delivered by mail. If a participant had not returned the completed survey within three weeks, they were contacted by telephone to verify receipt of the study package. Illiterate or physically disabled participants were offered a telephone interview or other assistance if they were unable to complete the selfadministered survey. The PHQ consisted of 74 questions, addressing such issues as bowel screening history, medical conditions, use of medication, diet, physical activity, consumption of alcohol and tobacco, and socio-demographic measures such as education and income. Furthermore, demographic information such as sex, age, date of birth, and marital status was collected. For female participants, there were additional questions relating to reproductive factors [21]. The FFQ administered in the ON portion of the study was the well-known Hawaii FFQ [22, 23]. The FFQ administered in NL was a modified version of the ON questionnaire that had been developed specifically to account for the unique food consumption patterns in NL
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[21]. The NL questionnaire is very similar to the FFQ used in ON; however, some food items that are not commonly consumed as part of the NL diet were excluded, and some food items commonly consumed in NL but not included in the Hawaii FFQ were added to the questionnaire. The NL questionnaire consisted of 169 items organized into 11 categories and required participants to recall their eating habits from 1 year prior to their diagnosis. The analytical sample sizes for the present study, based on the personal history questionnaire, were 703 cases and 717 controls, all residents of NL. Analysis was carried out on only those participants who completed both the PHQ and FFQ and for whom case/control status was available, resulting in a total sample size of 1,204 (518 cases and 686 controls). Controls were frequency matched with cases on age (5-year intervals) and sex. For the purpose of this paper, selected personal and nutritional characteristics were examined as well as pickled and red meat intake. Comparisons were made between cases and controls for all variables stratified by sex. Red meat, for the purpose of this paper, is defined as any meat other than chicken or fish. This designation was made in the PHQ, which defined beef, steak, hamburger, prime rib, ribs, beef hot dots, beef-based processed meat, veal, pork, bacon, pork sausage, ham, lamb, and venison as red meat [21]. Pickled meats are defined as meats that have been preserved in a brine solution. A serving of red meat, as described in the survey, was 2–3 oz, or a portion about the size of a deck of cards. Red meat doneness was derived from a combination of the number of servings of meat that were prepared by broiling or grilling and the degree to which this meat was cooked. Four doneness categories were created: B2 servings of rare-regular red meat per week, B2 servings of well-done red meat per week, [2 servings of rare-regular red meat per week, and [2 servings of well-done red meat per week. In order to control for major possible confounders, the following covariates were included in the multivariate logistic regression: sex, age, BMI, smoking status, level of education, level of physical activity, presence of inflammatory bowel disease, non-steroidal anti-inflammatory (NSAID) use, dietary intake of fruits, vegetables, dietary fiber, saturated fat, alcohol, cholesterol, folic acid, and caloric intake. Participants were classified as either male or female. Subjects were divided into four age categories: 18–49 years of age, 50–59 years of age, 60–69 years of age, 70 or greater years of age. While controls were frequency matched for age, recruiting older controls was found to be difficult, resulting in an age distribution that differed between cases and controls. Because of this, age was included as a covariate. The logistic regression was conducted using several different methods of age categorization,
1515
as well as using age as a continuous variable, with similar results being produced. Because of this, the above age categorization was used. Three categories were used to classify participants for BMI: \24.9 (underweight and normal), 25–29.9 (overweight), and C30 (obese). For smoking status, subjects were classified as either nonsmokers, former smokers, or current smokers. Participants were divided into four categories based on their level of education: 0–11 years of education; graduation from high school; vocational, technical or some college or university; and a bachelor’s or graduate degree. Physical activity was measured in average weekly lifetime physical activity MET hours. PA MET hours were calculated by taking the total number of metabolic hours of activity derived from the hours spent engaging in various activities after reaching the age of 20, divided by the number of weeks after each participant turned 20. These values were then divided into four categories: 0–7.38, 7.39–22.39, 22.40–53.03, and 53.04 and above. Subjects were classified as having had inflammatory bowel disease if they had ever been diagnosed with Crohn’s disease or colitis. Subjects were classified as having used NSAIDs if they had ever taken aspirin or ibuprofen. The intake of fruits, vegetables, dietary fiber, saturated fat, and alcohol were measured in grams per day, cholesterol in milligrams per day, folic acid in micrograms per day, and caloric intake in kilocalories per day. These values were derived from the FFQ and divided into tertiles.
Data analysis Initial descriptive statistics for both men and women were calculated, and the significance of the difference between cases and controls for these characteristics was assessed using chi-square analysis. The differences between cases and controls with respect to the mean intake of selected nutrients were evaluated using Student’s t-test. Prior to analysis, outliers were removed from the data by deleting observations with unlikely nutrient values (extremely low or high), which accounted for less than 5% of the total observations. As pickled meat is part of total red meat, two separate logistic regression analyses with identical other covariates were performed on the tertiles of pickled meat and total red meat consumption in grams per day, respectively. The following variables were included in the logistic regression analyses: age; BMI; smoking status; level of education; level of physical activity; presence of inflammatory bowel disease; non-steroidal anti-inflammatory (NSAID) use; dietary intake of fruits, vegetables, dietary fiber, saturated fat, alcohol, cholesterol, folic acid, and caloric intake. For all analyses, a p value of \0.05 was considered to be statistically significant. All statistical analyses were performed using SAS version 9.1 [24].
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Ethical considerations
controls had higher levels of education and higher incomes (Table 1). For the assessment of dietary intakes, men were found to have significantly different mean intakes of kilocalories, fat, protein, saturated fat, mono- and polyunsaturated fats, cholesterol, carbohydrate, and folic acid between cases and controls (Table 2). For women, the same nutritional variables were assessed; however, significant differences between cases and controls were observed only for caloric intake, saturated fat intake, and folic acid intake. Overall, a weak positive association was detected between the total number of servings of red meat consumed per week and the risk of CRC for female participants. However, this association was not statistically significant
Ethics approval for this study was obtained from the Human Investigation Committee, Faculty of Medicine, Memorial University of Newfoundland.
Results Male cases and controls had similar levels of weekly physical activity; however, cases had a higher BMI, lower levels of education, lower income, and were more likely to be smokers. Female cases were similar in BMI, smoking status, and level of weekly physical activity, but female
Table 1 Distribution of sociodemographic characteristics of the study population by case/control status and sex Males a
p
Females
a
a
Cases n = 277 (%)
p a
Cases n = 426 (%)
Controls n = 342 (%)
Controls n = 250 (%)
18–49
43 (10.1)
46 (13.5)
–
22 (7.9)
30 (12)
–
50–59
98 (23.0)
97 (28.4)
–
84 (30.3)
88 (35.2)
–
60–69
160 (37.6)
137 (40.1)
–
105 (37.9)
93 (37.2)
–
125 (29.3)
62 (18.1)
66 (23.8)
39 (15.6)
0.054
Age
70? BMI 15 to \25 (underweight and normal)
0.003
94 (23.1)
87 (25.9)
–
109 (42.2)
98 (40.3)
–
C25 to \30 (overweight)
183 (45.0)
175 (52.1)
–
93 (35.2)
90 (37.0)
–
[30 (obese)
130 (31.9)
74 (22.0)
0.010
62 (23.5)
55 (22.6)
0.913
201 (47.6)
103 (30.4)
–
129 (47.3)
78 (31.6)
– –
Level of education \11 Years High school graduate
63 (14.9)
52 (15.3)
–
46 (16.9)
40 (16.2)
128 (30.3)
131 (38.6)
–
72 (26.4)
90 (36.4)
–
30 (7.1)
53 (15.6)
26 (9.5)
39 (15.8)
0.001
21 (5.5)
20 (6.5)
–
34 (14.5)
23 (10.7)
–
$12,000–$29,999
156 (41.2)
80 (26.1)
–
96 (40.9)
69 (32.1)
–
$30,000–$49,999
120 (31.7)
92 (30.0)
–
61 (26.0)
53 (24.7)
–
$50,000 or more
82 (21.6)
115 (37.5)
44 (18.7)
70 (32.6)
0.007
Vocational/technical or some college Bachelor’s or graduate degree
\0.0001
Level of income $0–$11,999
\0.0001
Average weekly total lifetime physical activity MET hours 0 to \7.38 7.38 to \22.39 22.39 to \53.03
117 (28.0)
85 (25.3)
–
100 (36.4)
70 (28.5)
–
66 (15.8)
67 (19.9)
–
54 (19.6)
66 (26.8)
–
78 (18.7)
69 (20.5)
–
48 (17.5)
54 (22.0)
–
157 (37.6)
115 (34.2)
0.357
73 (26.6)
56 (22.8)
0.058
Yes
346 (81.2)
250 (73.1)
–
156 (56.3)
129 (51.6)
–
No
80 (18.8)
92 (26.9)
0.007
121 (43.7)
121 (48.4)
0.278
C53.03 Smoking
b
a
The numbers do not always add up to the total as a result of missing data
b
Smoking was defined as having ever smoked at least one cigarette/day for three months or more
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Table 2 Summary statistics for the consumption of selected nutrients by Newfoundland and Labrador study population Dietary Males variable Case
Females Control
p
Case
Control
p
Energy (kcal/day) x
2,366.78 2,189.27
SD N
2,418.33 2,224.31
803.05 293
752.94 293
x
83.06
74.94
81.92
SD
32.88
30.51
32.33
0.006
873.51 202
702.50 370 0.007
Fat (g/day)
N
296
290
0.002
198
77.17 29.92 377
0.079
Protein (g/day) x
97.44
90.70
95.69
92.53
SD
33.64
31.67
35.37
28.99
N
296
291
0.013
203
373
0.277
Saturated fat (g/day) x
28.04
25.62
28.71
SD
11.42
10.98
11.99
N
289
288
0.010
200
26.66 11.05 376
0.041
Monounsaturated fat (g/day) x SD N
30.51 12.73 296
27.60 11.38 290
29.84 12.25 0.004
198
28.37 11.66 377
0.157
(OR 1.81, 95% C.I., 0.94–3.51). The majority of study participants consumed two or fewer servings of red meat per week. The results of the red meat analysis are presented in Table 3. No significant association was observed between the degree to which meat was cooked (doneness) and CRC for men (OR 1.44, 95% C.I., 0.76–2.72) or women (OR 3.10, 95% C.I., 1.11–8.69) when participants who consumed more than two servings of well-done meat per week were compared to participants who consumed two or fewer servings of rare/regular meat per week. The results of the logistic regression for pickled meat showed a positive association between the consumption of pickled meat and colorectal cancer after controlling for potential confounders (Table 3). Male and Female participants in the highest tertile of pickled meat consumption were found to be 2.07 and 2.51 (95% C.I., 1.37–3.15; 1.45– 4.32) times as likely to have been diagnosed with CRC as those in the lowest tertile of consumption. A test for linear trend was performed for these results, and a p value indicating a significant linear trend was observed (p \ 0.0001) The categorization of age in these analyses may not be appropriate for CRC, a very age-dependant cancer; however, when the logistic regression analysis was performed using age as a continuous variable, similar results were produced.
Polyunsaturated fat (g/day) x SD N
16.18
14.72
16.18
6.84
6.49
6.67
296
287
0.009
15.22
Discussion
6.29
199
376
0.091
Cholesterol (mg/day) x
319.76
281.17
312.96
301.10
SD
132.84
123.15
136.53
127.24
N
290
290
200
378 288.08
\0.001
0.299
Carbohydrate (g/day) x
298.06
277.39
305.24
SD
107.84
101.90
107.28
100.06
N
293
290
200
374
0.018
0.057
Folic acid (lg/day) x SD N
85.21 47.89 288
69.96 44.23 290
84.78 48.86 \0.0001
197
71.40 44.39 376
0.001
Dietary fiber (g/day) x SD N
20.97
20.69
21.82
8.62
9.32
8.44
298
287
0.711
202
21.53 9.21 378
0.709
Alcohol (g/day) x SD N
7.91
7.19
6.08
6.31
11.68
11.17
10.03
10.00
292
287
0.449
200
378
0.794
Our study contributes to the existing literature in two respects. First, it offers the first and fullest explicit published study examining the association between pickled meat and colorectal cancer. It was found that the level of consumption of pickled meat did have a significant effect on the case/control status for this group of participants. The odds ratios produced also showed a clear dose–response relationship. These findings are consistent with findings from similar studies [25–27]. In addition to its scientific contributions, given the highest incidence rate of CRC in Canada, the insights gained from this study on pickled meat intake and CRC are of great public health importance. Since pickled meat is commonly consumed in this population, reducing pickled meat intake may be a meaningful approach to reduce the risk of CRC [17]. Trimmed naval beef and cured pork riblets, two common pickled meats included in the diets of many residents of NL, include sodium nitrite as one of the preserving agents. It has been suggested that nitrite/nitrate compounds can be converted to n-nitroso compounds in food and that these n-nitroso compounds are carcinogens [28–31].
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Table 3 ORs and 95% CI for CRC associated with the consumption of selected nutrients in grams per day (divided into tertiles) and selected personal characteristics in the Newfoundland and Labrador study population Variable
Sex
Case M
Pickled meata
I (\1)
Red meatb
Red meat donenessb
Daily caloric intake
a
Vegetable intakea
Folic acid intakec
Cholesterol intaked
Total dietary fibera
Alcohol intake
Level of education
Avg. weekly MET Hours.
F
M
F
M
F
96
247
175
1.00
1.00
–
–
24
41
36
1.64
1.03
0.89–3.02
0.49–2.17
III ([3) B2
132 125
90 81
115 159
72 131
2.07 1.00
2.51 1.00
1.37–3.15 –
1.45–4.32 –
[2 to B3
74
41
83
63
0.96
1.14
0.59–1.57
0.61–2.11
[3 to B5
49
40
73
41
0.95
1.46
0.56–1.59
0.73–2.93
[5
53
39
78
44
0.75
1.81
0.43–1.29
0.94–3.51
B2 ‘‘rare/regular’’
71
17
115
46
1.00
1.00
–
–
B2 ‘‘well-done’’
132
106
165
141
1.23
1.94
0.76–2.00
0.81–4.62
[2 ‘‘rare/regular’’
18
10
24
14
1.42
3.95
0.61–3.33
1.02–15.25
[2 ‘‘well-done’’
42
32
51
28
1.44
3.10
0.76–2.72
1.11–8.69
I (\1,888.2)
93
61
157
74
1.00
1.00
–
–
II (1,888.2–2,542.7)
87
62
142
94
0.72
0.75
0.38–1.37
0.35–1.61
III ([2,542.7)
113
77
93
102
1.18
1.11
0.47–2.98
0.36–3.45
I (\246.6)
102
68
151
80
1.00
1.00
–
–
II (246.6–390.8)
111
69
124
98
1.10
0.88
0.66–1.82
0.46–1.67
95
73
128
105
0.77
0.75
0.42–1.39
0.36–1.56
I (\138.1) II (138.1–299.7)
103 98
65 73
152 131
81 100
1.00 0.97
1.00 0.86
– 0.59–1.58
– 0.45–1.63
III ([299.7)
107
72
120
102
1.52
1.03
0.84–2.76
0.48–2.19
73
58
153
99
1.00
1.00
–
–
I (\49.9) II (49.9–89.1)
107
49
135
93
2.16
1.04
1.32–3.53
0.57–1.92
III ([89.1)
108
90
103
82
2.13
1.71
1.22–3.69
0.91–3.18
I (\236.5)
88
61
160
76
1.00
1.00
–
–
II (236.5–332.4)
93
65
128
100
1.11
0.82
0.65–1.90
0.43–1.54
III ([332.4)
108
74
104
99
1.12
0.85
0.57–2.19
0.39–1.89
I (\16.7)
108
58
148
74
1.00
1.00
–
–
88
73
129
99
0.65
1.20
0.36–1.18
0.56–2.56
102
71
119
96
0.67
0.84
0.31–1.45
0.31–2.29
I (\20.9)
85
57
166
76
1.00
1.00
–
–
II (20.9–30.2)
99
69
121
95
1.79
0.78
1.00–3.20
0.38–1.61
III ([30.2)
104
74
105
101
0.99
0.55
0.43–2.27
0.21–1.43
I (\1)
118
91
172
129
1.00
1.00
–
–
II (1–5.9) III ([5.9)
63 111
51 58
87 132
60 85
1.23 1.10
1.23 1.10
0.67–2.26 0.62–1.93
0.67–2.26 0.62–1.93
\11 Years
144
104
134
87
1.00
1.00
–
–
High school
49
36
57
47
0.49
0.49
0.25–0.98
0.25–0.98
Vocational/technical
91
51
152
100
0.38
0.38
0.20–0.70
0.20–0.70
University or higher
22
15
56
46
0.30
0.30
0.12–0.74
0.12–0.74
\7.38
98
81
95
78
1.00
1.00
–
–
7.38 to \22.39
45
46
78
73
0.73
0.73
0.38–1.42
0.38–1.42
51
30
81
61
0.79
0.79
0.40–1.58
0.40–1.58
108
51
143
68
1.11
1.11
0.59–2.09
0.59–2.09
22.39 to \53.03 C53.03
123
M
37
III ([24.1)
a
95% CI
139
II (16.7–24.1) Total saturated fata
F
OR
II (1–3)
III ([390.8) Fruit intakea
Control
Cancer Causes Control (2010) 21:1513–1521
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Table 3 continued Variable
Sex
Case M
BMI category
Control F
M
OR F
M
95% CI F
M
F
15 to \25
72
81
98
112
1.00
1.00
–
–
25 to \30
134
73
199
97
0.66
0.66
0.37–1.19
0.37–1.19
89
46
98
66
0.59
0.59
0.31–1.13
0.31–1.13
C30
ORs estimated from logistic regression, adjusted for age, BMI, smoking status, level of education, intake of vegetables, fruit, folic acid, cholesterol, dietary fiber, saturated fat, alcohol, caloric intake, level of physical activity, NSAID use, and the presence of inflammatory bowel disease a
Numbers refer to tertiles of consumption in grams per day
b
Categories for this variable are servings/day from PHQ
c
Numbers refer to tertiles of consumption in lg per day
d
Numbers refer to tertiles of consumption in milligrams per day
Research by Tricker and Preussmann showed that cured meats, which the authors defined as meat that had been preserved using nitrite, nitrate, or a combination of both, were major sources of many n-nitroso compounds in the diet [32]. While many of the experiments involving these compounds involve animals, it has been suggested that nnitroso compounds such as N-Nitrosodimethylamine (NDMA) may be even more potent as carcinogens in humans than in animal models [28]. Second, in comparison with the results from the Ontario data [13], which was part of the same project and showed significant positive association between red meat intake and CRC, this study provides additional evidence that the effects of red meat intake on CRC may vary from one population to another. The differences observed between the two provinces suggest that red meat intake is more likely to work with other factors (i.e., genetic and/or environmental) rather than independently to give rise to CRC. Thus, our findings may help with the development of new research questions that assist us to better understand this disease. Many studies have shown a positive association between the consumption of red meat and colorectal cancer [25, 33–35]. First, unlike the results reported in many previous studies, our study did not find a significant positive association between red meat intake and CRC. While we are unable to offer a definite explanation of this, there are several plausible reasons. First, ‘‘red meat’’ is an umbrella term, which includes several animal meat products. Different from many other places in North America, NL population consumes substantially more red meat from wild animals, such as moose and caribou, particularly in winter seasons. As no published research work examining the effect of wild red meat on CRC is available, we cannot go beyond a simple speculation in this regard. Second, NL has the highest rate of CRC in Canada and the highest rate of familial CRC in the world, and participated in many genetic research studies for the detection of
novel CRC-causing genes. This may have raised public health awareness and caused gradual diet changes in the general population and particularly so in high-risk individuals. If this is true, it would introduce differential exposure bias between cases and controls, leading to a lower estimation of the true effect of red meat. Additionally, NL is a geographically isolated region with fewer choices in the food supply. As a result, there was less variation of red meat consumption in this population, and consequently the effects were less likely to be detected. Yet, another possible reason for this may be that Newfoundland and Labrador, a founder population with a high incidence of colorectal cancer, has a higher proportion of cases of CRC, which result primarily from a genetic cause [36]. This, in turn, may overshadow some of the environmental effects such as red meat consumption [36]. Since we collected blood samples from the participants, we plan to explore this further in our future studies. This study had a relatively large sample size (1,204). This, coupled with the fact that a personal history questionnaire was administered to the same subjects who completed the FFQ, allowed for the assessment and investigation of many other factors that may be associated with CRC. The examination of these factors allowed for the control of variables that could act as potential confounders for the items of interest. In this study, recall bias may present a problem as it does in any situation that requires participants to provide detailed information from the past; in this case, 1 year prior to completing the surveys. Cases were aware of their disease status prior to completing the FFQ. While it is possible that knowledge of their diagnosis may have affected responses given by participants regarding the consumption of foods thought to be associated with CRC, it has been suggested that in case–control studies, reliability of recall does not differ significantly between cases and controls [37]. As the data used in this study were collected as part of a larger project involving participants from both NL and ON,
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additional analysis of the Ontario data for similar associations between meat consumption and CRC is necessary. Unfortunately, this is not possible for the type of meat examined in this paper as pickled meat consumption is rare in ON and thus was not included in the ON FFQ. The uniqueness of the traditional Newfoundland and Labrador diet makes it ideal for comparison with the Ontario data, which would be expected to be more typical of the diets of the majority of Canadians. It is possible as well that more than one dietary pattern may be identified in Newfoundland and Labrador, for example a Traditional versus Canadian diet, which would allow for comparisons within the province and for these diets with the Ontario data. Additionally, as genetic data were also collected as part of this study, an attempt will be made to link the nutritional and genetic data for both provinces and to draw conclusions based on it. A person’s diet is modifiable. It is important that dietary risk factors for CRC are identified so that informed decisions regarding a person’s diet can be made in an effort to minimize the risk of developing CRC. The findings in this study provide evidence for the hypothesis that the intake of pickled meat is positively associated with the risk of CRC in the study subjects. Acknowledgments This work was supported by the Canadian Institutes of Health Research Team Grant [CIHR-CPT79845] and Canadian Institutes of Health Research Team in Interdisciplinary Research on Colorectal Cancer Studentship [205835].
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