Vegetables and total cancer.
1) Total vegetables and total cancer risk.
Background: Almost all articles presented data stratified by gender. Therefore the choice was made to present results for men and women
separately. As a consequence, results from two cohorts will not be included in the following analysis: In "The Finnish Mobile Clinic Health Examination Survey
Cohort" (Knekt P [7]), and in "The Boyd Orr Cohort" (Maynard M [2003]. See extended table), including 1,480 cancer cases, no associations were found between
total vegetables consumption and total cancer risk: RR = 0.93 (0.74-1.17), and 1.34 (0.93-1.93; P = 0.27), respectively.
Men: Data for men was provided by 7 cohorts, including a total of 50,109 cases.
Weak, significant protective effects were found in 2 cohorts of very large size (Boffetta P [18], George SM [22]), including 44,675 cases (89% of all cases).
No associations were found in the remaining cohorts. The average RR = 0.95 (excluding incomplete data from Strandhagen E [9]).
Women: Data for women was provided by 5 cohorts, combining 45,371 cases.
A weak, significant protective effect was found in one cohort of very large size (Boffetta P [18]). But a weak, nonsignificantly increased risk (trend) was found
in another cohort of very large size (George SM [22]). No other associations were found. The average RR = 0.97.
Inclusion of intermediate levels of consumption:
Among men, (non)significant effects at any level of consumption are as follows:
- Boffetta P (18) Though the trend was significant, the RR was significant only at an intermediate level of consumption (209-306 g/d).
- George SM (22) Significant protective effects were found at 2 different levels of consumption (235-312 g/d, and > 424 g/d)
Among women, (non)significant effects at any level of consumption are as follows:
- Boffetta P (18) At ≥ 307 g/day.
- George SM (22) Though the trend showed a nonsignificantly increased risk, no RR differed (non)significantly from 1 at any level of consumption.
These analysis show that among men, signicant protective effects were found at an overlapping level of consumption (235-306 g/day). The effects size is RR = 0.95
(including data from the 3 cohorts which could be provided in this analysis), and therefore is identical to the overall effect size for high vs low consumption.
Effect modification.
Smoking status: Effects stratified by smoking status were provided by 4 cohorts (see extended table):
- George SM (22) A significant protective effect was found among the male part of the cohort (RR = 0.94; 95% CI = 0.91-0.97), but not among the male nonsmokers (RR = 0.97; 95% CI = 0.91-1.04).
- Takachi R (20) No effects were found among never smokers (HR = 0.97; 95% CI = 0.83-1.13), or ever smokers (HR = 0.94; 95% CI = 0.80-1.11).
- Boffetta P (18) Significant protective effects were found among never smokers (HR = 0.97; 95% CI = 0.96-0.99), and current smokers (HR = 0.97; 95% CI = 0.95-0.98), but not among past smokers (HR = 0.98; 95% CI = 0.96-1.00).
- Hung HC (11) No effects were found among never smokers (RR = 1.02; 95% CI = 0.94-1.10), past smokers (RR = 1.01; 95% CI = 0.94-1.08), or current smokers (RR = 0.94 (0.85-1.05).
Some results are hard to interpret. In one cohort results were only given for male never smokers (George SM [22]). And in another cohort, results were
only given for nonsmokers vs ever smokers, categorizing past-, and current smokers into one group (Takachi R [20]). Briefly, a small protective effect
among never smokers was found in one out of 4 cohorts, and no associations were found among past smokers in 2 cohorts. Also, a small protective effect
among current smokers was found in one out of 2 cohorts, and the RR tended to be lower than among the other groups in a second cohort (Hung HC [11]).
Average RR's are 0.98, 0.99, and 0.96 for never, past, and current smokers, respectively.
Alcohol drinking: The significant protective effect in one cohort of very large size was restricted to subjects with heavy alcohol consumption
(Boffetta P [18]. see extended table). No difference in effect was found in another cohort (Takachi R [20]).
Dietary supplement use: Some articles showed stronger evidence for a possible protective effect among non-users of multivitamins. (Pooled results from 2 cohorts;
Hung HC [11]) or dietary supplements (Olsen A [2005]). In contrast, the effect was slightly more protective among dietary supplement users in a fourth cohort
(Benetou V [18]).
Conclusion: Among men, weak significant protective effects were found in 2 cohorts of very large size, and no other associations were found. Total vegetables
consumption possibly protects against total cancer risk among men (- 5%). Though this evidence was restricted to an intermediate level of consumption (235-306 g/d),
the effect size was identical to the one for high vs low levels of consumption.
Among women, inconsistent findings were done. Inconclusive evidence was found for an association between total vegetables - at any level of consumption - and total
cancer risk.
Stratified analysis included the possibility that any protective effect may be stronger among current smokers. Inconclusive evidence was found for a
modifying effect of alcohol consumption and dietary supplement use.
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 22) George SM (2008) | The NIH-AARP Diet and Health Study | 35,071 | RR = 0.94 (0.91-0.97; P = 0.004). |
| 20) Takachi R (2007) | The JPHC Study | 1,925 | HR = 0.95 (0.82-1.10; P = 0.38). |
| 18) Boffetta P (2010) | The EPIC Study | 9,604 | HR = 0.95 (0.87-1.03; P = 0.04). |
| 15) Jansen MC (2004) | The Zutphen Elderly Study | 138 | RR = 0.83 (0.54-1.25; P = 0.36). |
| 11) Hung HC (2004) | The Health Professionals' Follow-Up Study | 2500 | RR = 0.99. |
| 9) Strandhagen E (2000) | The Study Of Men Born In 1913 | 226 | No significant association (no data shown). |
| 2) Shibata A (1992) | The Leisure World Study | 645 | 1.05 (0.89-1.27). |
| Total number of cases: 50,109 | Average RR = 0.95 |
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 22) George SM (2008) | The NIH-AARP Diet and Health Study | 15,792 | RR = 1.04 (0.98-1.09; P = 0.084). |
| 20) Takachi R (2007) | The JPHC Study | 1,305 | HR = 0.94 (0.78-1.12; P = 0.19). |
| 18) Boffetta P (2010) | The EPIC Study | 21,000 | HR = 0.92 (0.87-0.97; P = 0.005). |
| 11) Hung HC (2004) | The Nurses' Health Study | 6584 | RR = 0.99. |
| 2) Shibata A (1992) | The Leisure World Study | 690 | 0.84 (0.70-1.01). |
| Total number of cases: 45,371 | Average RR = 0.97 |
| Author | Cohort name | Cases | Relative Risk (RR) for never smokers | Relative Risk (RR) for past smokers | Relative Risk (RR) for current smokers |
|---|---|---|---|---|---|
| 22) George SM (2008) | The NIH-AARP Diet and Health Study | Not defined | RR = 0.97 (0.91-1.04; P = 0.47). | - | - |
| 20) Takachi R (2008) | The JPHC Study | 1,631 never smokers | HR = 0.97 (0.83-1.13; P = 0.26). | - | - |
| 18) Boffetta P (2010) | The EPIC Study | 13,728 never smokers, 8,832 past smokers, and 7,388 current smokers | HR = 0.97 (0.96-0.99). | HR = 0.98 (0.96-1.00). | HR = 0.97 (0.95-0.98). |
| 11) Hung HC (2004) | The Nurses' Health Study & The Health Professionals' Follow-up Study | 3,577 never smokers, 3,945 past smokers, and 1,694 current smokers | RR = 1.02 (0.94-1.10). | RR = 1.01 (0.94-1.08). | RR = 0.94 (0.84-1.05). |
| Average RR = 0.98 | Average RR = 0.99 | Average RR = 0.96 |
2) Total vegetables and total cancer mortality.
6 articles, providing information about 6 different cohorts were found. No associations were found in any cohort. The average RR was 1.07 (excluding
incomplete data from Strandhagen E [9], and Hung HC [11]).
Conclusion: No evidence was found for an association between total vegetables and total cancer mortality.
| Author | Cohort name | Cases | Sex | Relative Risk (RR) |
|---|---|---|---|---|
| 18) Nöthlings U (2008) | The EPIC Study | 319 | Men & Women | RR = 1.09 (0.87-1.39). |
| 13) Maynard M (2003) | The Boyd Orr Cohort | 158 | Men & Women | OR = 1.14 (0.75-1.72). |
| 11) Hung HC (2004) | The Nurses' Health Study & The Health Professionals' Follow-up Study | Not defined. | Men & Women | No significant association (no data shown). |
| 9) Strandhagen E (2000) | The Study Of Men Born In 1913 | 121 | Men | No significant association (no data shown). |
| 5) Sahyoun NR (1996) | No cohort name | 57 | Men & Women | RR = 0.80 (0.36-1.76; P = 0.82). |
| Total number of cases: 655 + X | Average RR = 1.07 |
| Author | Cohort name | Subjects | Years of follow-up | Cases | End point | Consumption of | Relative Risk (RR) | Adjustments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 22) George SM (2008) | The National Institutes of Health-AARP Diet and Health Study. | 195,229 women and 288,109 men aged 50-71. (USA) | 1995-2003 | 15,792 women, and 35,071 men | All cancer incidence | Vegetables (excluding potatoes) |
1 cup = 237 mL. One cup is 1 cup of raw/cooked vegetable, 1 cup of 100% juice, or 2 cups of raw leafy greens. Age, smoking (smoking status, time since quitting, and smoking dose), energy intake, BMI, alcohol, physical activity, education , race, marital status, family history, menopausal hormone therapy (women), and fruit intake. |
20) Takachi R (2008) | The Japan Public Health Center-based Prospective Study (JPHC). | 77,891 subjects (35,909 men 41,982 and women) aged 45-74. | (Japan) 5.8 | (1995-1998 to 2002) See variables | Risk of cancer | Vegetables (defined as: 6 pickled vegetables [Chinese radishes, green leafy vegetables, plums, Chinese cabbage, cucumbers, and eggplant], 7 cruciferous vegetables [cabbage, Chinese radishes, komatsuna, broccoli, Chinese cabbage, leaf mustard, and chard or Swiss chard], 6 green leafy vegetables [spinach, Chinese chives, garland chrysanthemums, chingensai, mugwort, and green pepper], 4 yellow vegetables [carrots, tomatoes, pumpkins, and tomato juice], and 7 other vegetables [onions, cucumbers, bean sprouts, snap beans, lettuce, bitter gourds, and loofah]) |
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Stratified analyses by cohort (cohort I or II), BMI, age, and alcohol intake (< 150 vs > or = 150 g ethanol/wk) showed similar results. age, public health center area, BMI, physical activity, smoking, alcohol, energy, screening examination, medication, and daily vitamin supplement use. |
18) Boffetta P (2010) | The EPIC Study | 142,605 men, and 335,873 women aged 25-70, and without cancer from 23 centers in 10 European countries. | 8.7 | (1992-2000 to 2002-2005) See variables | Total cancer incidence (excluding nonmelanoma skin cancer) | Total vegetables (excluding potatoes, other tubers, legumes, and vegetable juices) |
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Duration of follow-up did not change the results (data not shown). Stratified by center and sex. |
Adjusted for age, current amount of smoking, duration of smoking, time since quitting, smoking of pipe or cigar, occasional smoking and missing smoking information, alcohol intake, physical activity, educational level, height, weight, energy from fat sources, energy from nonfat sources, and for women age at menarche, pregnancy, oral contraceptive, use of HRT, and menopausal status. 18) Benetou V. (2008) | The Greek segment of the EPIC Study. | 25,623 subjects (10,582 men, and 15,041 women). | (Greece) 7.9 | (1994-99 to 2007) 851 | (421 men, and 430 women) Total cancer risk (excluding nonmelanoma skin cancer) | Vegetables (not defined) | HR = 0.96 (0.88-1.05; No P-value) for an increment of 230 g/day. | Stratified by sex. Adjusted for age, years of schooling, smoking status, BMI, height, physical activity, ethanol intake, supplement use, and total energy intake. |
18) Benetou V. (2008) | The Greek EPIC Cohort Study. | 25,623 participants (10,582 men, and 15,031 women). | 7.9 | 851 | (421 men, and 430 women) Total cancer incidence (excluding nonmelanoma skin cancer) | Vegetables including legumes (not defined) |
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There was no evidence that the association between vegetable and/or fruits and cancer occurrence is different among dietary supplement (not defined) users and nonusers - if anything, the inverse association was slightly more evident among the users (data not shown). Intake of dietary supplements is not uncommon among women, but is rather limited among men. Age, formal education, smoking status, BMI, height, physical activity, alcohol intake, supplement intake, and total daily energy intake. Fruits and vegetables are mutually adjusted for. |
18) Olsen A. (2005) | The Danish Diet, Cancer and Health Study (= part of the EPIC Cohort). | 29,068 women and 26,492 men. (Denmark) | ? | 1,844 women (1,456 users, 388 nonusers of supplements) and | 1,519 men (951 users, 568 nonusers of supplements) Total cancer risk | Vegetables (not defined) |
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Body mass index, alcohol intake, smoking, and hormone replacement therapy. |
15) Jansen MC. (2004) | The Zutphen Elderly Study | (Part of The Seven Countries Study). 730 men aged 65-84. | (The Netherlands) 10 | (1985-1995) 138 | Total cancer risk | Vegetables (not defined, 27 items excluding potatoes) |
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Age, smoking-status, pack-years of cigarette smoking, total energy intake, physical activity, BMI, alcohol intake, fruit intake, and vegetable intake when variety studied. |
13) Frobisher C. (2007) | The Boyd Orr Cohort. | A reproducibility study using data from 151 families in the Carnegie Survey of Diet and Health. | Background: Data from the original study came from 1,352 families (4,999 children) in the Carnegie Survey of Diet and Health (86.6% of these children were traced as adults and form the Boyd Orr cohort). (England & Scotland) No data shown. | No data shown. | Total cancer incidence | Vegetables (not defined) |
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ORs are for a 40 g/day increase in intake. Not defined. But probably --> |
Using ICCs: age, sex, energy intake, household food expenditure, Townsend score, season, district and social class. Using regression calibration: Age, sex, district of residence, season and Townsend score of district of last posting. This model takes account of the measurement errors in the estimation of the energy intakes and vegetable intakes and also of the measurement errors in the confounder, household food expenditure. 13) Maynard M. (2003) | The Boyd Orr Cohort. | 3.878 children -mean age 8 years- (1.959 women/1.919 men). (England/Scotland) | > 60 years (1937-39 to 2000) | 251 women, and 232 men. | Total cancer incidence | Vegetables (Not defined. Excluding potatoes) |
OR = 1.34 (0.93-1.93; P = 0.27) for the highest vs lowest quartile of consumption. | Amount specific data (mean intake in g/day): 23.1: OR = 1. 47.3: OR = 1.17 (0.84-1.64). 68.5: OR = 0.95 (0.66-1.34). 115.2: OR = 1.34 (0.93-1.93). Intra-family clustering. Age, sex, energy, food expenditure, Townsend score, season, and district. |
11) Hung HC. (2004) | The Nurses' Health Study | & The Health Professionals' Follow-up Study. 71,910 women (aged 30-55) and | 37,725 men (aged 40-75). (USA) 14 | (1984-1998) (women), and 12 (1986-1998) (men) 6584? women, and | 2500? men. 3577 never smokers, 3945 past smokers, and 1694 current smokers. 3128 non-vitamin supplement users, and 3948 multivitamin supplement users. All cancer risk (excluding nonmelanoma skin cancer, in situ breast cancer, and organ-confined prostate cancer) | All vegetables (tomatoes, tomato sauce, string beans, broccoli, cabbage or coleslaw, cauliflower, Brussels sprouts, carrots, corn, peas or lima beans, mixed vegetables, yellow [winter] squash, eggplant, zucchini, or other summer squash, yams or sweet potatoes, spinach, kale, mustard, or chard greens, iceberg or head lettuce, romaine or leaf lettuce, celery, mushrooms, beets, alfalfa sprouts, garlic, green or chili peppers, potatoes, artichokes, asparagus, avocado, bean sprouts, chicory, chili peppers, daikon radish, endive, escarole, jerusalem artichokes, turnips, kohlrabi, leeks, okra, oriental vegetables, parsley, parsnips, peapods, radishes, rhubarb, rutabagas, scallions, and water chestnuts) |
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All RRs are for an increment of 3 servings/day. Total calorie intake, age, smoking status, alcohol use, body mass index, multivitamin and vitamin E supplement use, physical activity, family history of myocardial infarction, family history of colon cancer, personal history of hypertension, personal history of hypercholesterolemia, personal history of diabetes, and (for women only) family history of breast cancer, menopausal status, and use of hormone replacement therapy. |
11) McCullough ML. (2000) | The Health Professionals Follow-up Study. | 38,622 men aged 40-75. | (USA) 8 | (1986-1994) 1,661? | Total cancer risk (all cancers except nonaggressive prostate cancer (< stage C and < grade 7) and nonmelanoma skin cancer) | Vegetables (Not defined, including potatoes) | Not associated with risk (no data shown). | Highest (10 points) vs lowest tertile (0 points) = 4.2-5 vs 0 servings/d respectively. Each component of the healthy food index was added individually into the multivariate model, adjusting for age, smoking, body mass index, alcohol intake, physical activity, total energy intake, and time period. |
9) Strandhagen E. (2000) | The Study Of Men Born In 1913. | 730 men aged 54. | (Sweden) 26 | (1967-1993) 226 | Cancer disease | Vegetables (not defined) | No significant association was found for men in the highest vs lowest quartile of consumption (6-7 vs 0-1 times/wk) (No data shown). | No data shown. |
7) Knekt P. (1997) | The Finnish Mobile Clinic Health Examination Survey Cohort. | 9,959 men and women aged 15-99. | (Finland) 24 | (1967-1991) 997? | All cancer risk | Vegetables other than onions | RR = 0.93 (0.74-1.17; No P-value) for the highest vs lowest quartile of consumption (not defined). | (For onions, also no association was found: RR = 1.02 (0.84-1.25; No P-value) Sex, age, geographic area, occupation, smoking, BMI, and intakes of energy, vitamin C, vitamin E, beta carotene, fiber, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and cholesterol. |
2) Shibata A. (1992) | The Leisure World Study. | 11,580 residents of a retirement community. | (USA) 1981-1989 | 1,335 (645 men, 690 women) | All cancer risk | Vegetables (Leafy green lettuce [Romaine, Boston, bibb, butterhead, endive, escarole, salad bowl, red leafy lettuce], other leafy greens [spinach, chard, beet greens, turnip greens, mustard greens, collards, kale, dandelion greens], iceberg or head lettuce, cabbage [incude sauerkraut and coleslaw], white potatoes or turnips, sweet potatoes, yams, pumpkin [including in pie or soup], carrots, winter squash [butternut, hubbard, acorn squash [including in pie or soup], summer squash [zucchini, yellow crookneck, yellow straightneck, cocozelle, scallop squash, broccoli, tomatoes [fresh or cooked, including tomatoes in a sauce such as spaghetti or tomato soup], green peas [including snow peas and Chines pea pods], green beans or string beans, lima beans or blackeye beans, corn, asparagus, sweet green peppers, sweet red peppers, hot red chili peppers [including hot pepper sauce, chili powder, cayenne pepper, tobasco sauce, Brussels sprouts, cauliflower) |
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Age and smoking. |
Adjustment for BMI or physical activity did not materially alter the results (data not shown).
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