Fruit and total cancer.
1) Total fruit 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: "The Finnish Mobile Clinic Health Examination Survey
Cohort" (Knekt P [7]), and "The Boyd Orr Cohort" (Maynard M [2003]. See extended table), including 1,480 cancer cases. A significant protective effect
was found in the cohort of very small size (OR = 0.62; 95% CI = 0.43-0.90; P = 0.02 for Maynard M [13]), but no association was found in the other cohort
(RR = 0.90; 95% CI = 0.71-1.14 for Knekt P [7]).
Men: Data for men was provided by 8 cohort, including a total of 50,210 cases.
Significant protective effects were found in 2 cohorts (Jansen MC [15], Boffetta P [18]), including 9.742 cases (19% of all cases). No other associations were found,
but RRs were ≤ 1. The average RR = 0.96 (excluding incomplete data from Strandhagen E [9]).
Women: Data for women was provided by 6 cohorts, including a total of 45,502 cases.
(Non)significant protective effects were found in two cohorts of (very) small size (Shibata A [2], Cox BD [10]), including 821 cases. And a nonsignicant protective
effect was found in another cohort, though the trend but not the RR was nonsignificant (George SM [22]). The average RR = 0.99.
Inclusion of intermediate levels of consumption:
Among men, (non)significant effects at any level of consumption are as follows:
- Boffetta P (18) Nonsignificant protective at 163-246 g/day. Significant protective at ≥ 247 g/day.
- Jansen MC (15) Significant protective at > 200 g/day.
Among women, (non)significant effects at any level of consumption are as follows:
- George SM (22) Though the trend showed a nonsignificant protective effect, no RR differed (non)significantly from 1 at any level of consumption.
- Boffetta P (18) Significant protective at 163-246 g/day.
- Cox BD (10) Though risk decreased per frequency category of consumption, the cagegorized models showed no evidence for an effect at any level of consumption.
- Shibata A (2) Significant protective at ≥ 192 g/day.
These analysis show no consistent effects at any intermediate level of consumption.
Effect moficiation.
Smoking status: Effects stratified by smoking status were provided by 3 cohorts (see extended table):
- Takachi R (20) No effects were found among never smokers (HR = 1.12; 95% CI = 0.95-1.33; P = 0.83), or ever smokers (HR = 0.95; 95% CI = 0.79-1.14; P = 0.79).
- Boffetta P (18) Any possibly protective effect seemed to be restricted to current smokers (HR = 0.98; 95% CI = 0.97-1.00), though the effect size was very weak. No associations were found among never smokers (HR = 1.00; 95% CI = 0.99-1.01), and former smokers (HR = 0.99; 95% CI = 0.98-1.01).
- Hung HC (11) No effects were found among never smokers (RR = 1.03; 95% CI = 0.94-1.12), past smokers (RR = 0.97; 95% CI = 0.89-1.06), or current smokers (RR = 1.07 (0.94-1.22).
In one cohort cohort, results were only given for nonsmokers vs ever smokers, categorizing past-, and current smokers into one group (Takachi R [20]).
No significant effects were found in any cohort for any subgroup, stratified by smoking status. RR's were ≥ 1 among never smokers in all 3 articles,
examining 4 cohorts.
Average RRs are 1.02, 0.98, and 1.00 for never, past, and current smokers, respectively.
Alcohol drinking: Results from one cohort of very large size were presented, stratified by drinking status (Boffetta P [18]). Though no significant
effects were found in all 3 subgroups of drinkers, the effect size suggests any possible protective effect may be restricted to heavy drinkers
(HR = 0.96; 95% CI = 0.93-1.00). No associations were found among weak drinkers (HR = 1.00; 95% CI = 0.99-1.01), or moderate drinkers
(HR = 0.99; 95% CI = 0.97-1.00).
Dietary supplement use: One article showed stronger evidence for a possible protective effect among non-users of multivitamins. (Pooled results from 2 cohorts;
Hung HC [11]). In contrast, the effect was slightly more protective among dietary supplement users in a third cohort (Benetou V [18]). No difference in
effect of dietary supplements was found in a fourth cohort (Olsen A [2005]).
Conclusion: Some protective effects were found, but these were restricted to few cohorts, inluding a small minority of the total amounts of cases. Also, the
average RR's (adjusted for the amounts of cases/cohort) showed little evidence for an effect. Stratified analysis showed inconclusive evidence for a modifying effect of
alcohol drinking, or use of dietary supplements. Analysis stratified by smoking status showed that any protective effect among never smokers seems very unlikely since
all 3 RR's were ≥ 1.
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 22) George SM (2008) | The NIH-AARP Diet and Health Study | 35,071 | RR = 0.98 (0.95-1.02; P = 0.17). |
| 20) Takachi R (2007) | The JPHC Study | 1,925 | HR = 0.90 (0.77-1.07; P = 0.29). |
| 18) Boffetta P (2010) | The EPIC Study | 9,604 | HR = 0.89 (0.82-0.97; P = < 0.001). |
| 15) Jansen MC (2004) | The Zutphen Elderly Study | 138 | RR = 0.62 (0.40-0.96; P = 0.04). |
| 11) Hung HC (2004) | The Health Professionals' Follow-up Study | 2,500 | RR = 0.98. |
| 10) Cox BD (2000) | The British HALS | 101 | Fruit in winter: OR = 0.91 (0.78-1.06; P = 0.23). Fruit in summer: OR = 1.00 (0.85-1.17; P = 0.97). |
| 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 | RR = 0.94 (0.78-1.14). |
| Total number of cases: 50,210 | Average RR = 0.96 |
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 22) George SM (2008) | The NIH-AARP Diet and Health Study | 15,792 | RR = 0.99 (0.94-1.05; P = 0.059). |
| 20) Takachi R (2007) | The JPHC Study | 1,305 | HR = 1.14 (0.93-1.39; P = 0.29). |
| 18) Boffetta P (2010) | The EPIC Study | 21,000 | HR = 0.97 (0.92-1.02; P = 0.5). |
| 11) Hung HC (2004) | The Nurses' Health Study | 6,584 | RR = 1.02. |
| 10) Cox BD (2000) | The British HALS | 131 | Fruit in winter: OR = 0.87 (0.76-1.00; P = 0.052). Fruit in summer: OR = 0.88 (0.75-1.02; P = 0.097). |
| 2) Shibata A (1992) | The Leisure World Study | 690 | RR = 0.76 (0.63-0.91; P = < 0.05). |
| Total number of cases: 45,502 | Average RR = 0.99 |
| Author | Cohort name | Cases | Relative Risk (RR) for never smokers | Relative Risk (RR) for past smokers | Relative Risk (RR) for current smokers |
|---|---|---|---|---|---|
| 20) Takachi R (2008) | The JPHC Study | 1,631 never smokers | HR = 1.12 (0.95-1.33; P = 0.83). | - | - |
| 18) Boffetta P (2010) | The EPIC Study | 13,728 never smokers, 8,832 past smokers, and 7,388 current smokers | HR = 1.00 (0.99-1.01). | HR = 0.99 (0.98-1.01). | HR = 0.98 (0.97-1.00). |
| 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 = 1.03 (0.94-1.12). | RR = 0.97 (0.89-1.06). | RR = 1.07 (0.94-1.22). |
| Average RR = 1.02 | Average RR = 0.98 | Average RR = 1.00 |
2) Total fruit and total cancer mortality
12 articles, providing information about 11 different cohorts were found including a total of > 5,052 cases (no data was available from 2 cohorts: Hung HC; 2004).
Significant protective effects were found in 2 cohorts, including 3,816 cases (4, 14), though in one cohort the association was significant for men only (4). In addition,
a nonsignificant protective effect was found in a third cohort examining men only, and including 114 cases (6). No other associations were found. The effect was of
moderate size (excluding incomplete data from Strandhagen E [9], and Hung HC [11]: Average RR = 0.88).
Conclusion: Significant protective effects were found in 2 cohorts. Within one cohort, an effect was found for daily vs less frequent
consumption (4), and in the other one for (almost) daily consumption vs < 2 servings/wk (14), indicating that a protective effect may only be found compared with
very low or infrequent consumption. Since no data about the amount of cancer cases was available from 2 cohorts, evidence was judged suggestive for a protective effect
of total fruits against total cancer mortality for daily vs less frequent consumption (- 11%).
| Author | Cohort name | Cases | Sex | Relative Risk (RR) |
|---|---|---|---|---|
| 18) Nöthlings U (2008) | The EPIC Study. | 319 | Men & Women | RR = 1.08 (0.98-1.19). |
| 16) Khan MM (2004) | No cohort name. | 155 men, and 89 women | Men & Women | Men: RR = 1.00 (0.6-1.6). Women: RR = 1.1 (0.4-2.9). |
| 14) Sauvaget C (2003) | The Hiroshima/Nagasaki Life Span Study. | 3,136 | Men & Women | RR = 0.88 (0.80-0.96; P = 0.0044). |
| 13) Maynard M (2003) | The Boyd Orr Cohort. | 158 | Men & Women | OR = 0.73 (0.47-1.11; P = 0.17). |
| 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). |
| 8) Whiteman D (1999) | The OXCHECK Study. | 223 | Men & Women | RR = 0.91 (0.63-1.32). |
| 6) Hertog MG (1996) | The Caerphilly Study | 114 | Men | RR = 0.5 (0.3-1.0). |
| 5) Sahyoun NR (1996) | No cohort name. | 57 | Men & Women | RR = 1.26 (0.53-2.99; P = 0.96). |
| 4) Appleby PN (2002) | The Health Food Shoppers Study. | 680 | Men & Women | Men: RR = 0.72 (0.56-0.93; P = < 0.05). Women: 0.88 (0.68-1.13). |
| Total number of cases: 5,052 + X | Average RR = 0.88 |
| 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 | Fruit |
1 cup = 237 mL. One cup is 1 cup of raw/cooked fruit, 1 cup of 100% juice, or 0.5 cup of dried fruit. 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 vegetable 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 | Fruits (defined as: mandarins, oranges, and 100% orange juice, papaya, apples, persimmons, strawberries, grapes, melons, watermelons, peaches, pears, kiwi fruit, pineapple, bananas, and 100% apple juice) |
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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 fruits (90% comprised of fresh fruits, and including dried an canned fruits, but not fruit 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) | Fruits including nuts (not defined) | HR = 1.01 (0.93-1.09; No P-value) for an increment of 205 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) | Fruits (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 | Fruits (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 | Fruit (strawberries, berries, grapes, peaches, cherries, prunes, and apricots) |
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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 | Fruit (not defined) |
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ORs are for a 40 g/day increase in intake. 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 fruit 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 | Fruit (not defined) |
OR = 0.62 (0.43-0.90; P = 0.02) for the highest vs lowest quartile of consumption. | Amount specific data (mean intake in g/day): 0.6: OR = 1. 12.7: OR = 0.66 (0.48-0.90). 31.3: OR = 0.70 (0.51-0.97). 88.4: OR = 0.62 (0.43-0.90). There was no evidence of interaction between fruit intake and either sex or age in their relation to cancer risk. 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 fruit (raisins or grapes, prunes, bananas, cantaloupes, watermelon, fresh apples or pears, oranges, grapefruit, strawberries, blueberries, peaches, apricots or plums, blackberries, cherries, currants, dates, fruit cocktail, guavas, honeydew melon, kiwi fruit, lemons, limes, mangoes, crenshaw melon, nectarines, persimmons, pineapple, plantains, pomegranates, quince, raspberries, tangerines, applesauce and dried apples, figs, papaya) |
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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) | Fruit (not defined) | Not associated with risk (no data shown). | Highest (10 points) vs lowest tertile (0 points) = 3.2-4 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. |
10) Cox BD. (2000) | The British Health and Lifestyle Survey (HALS). | 1,442 men, and 1,875 women aged 35-75. | 7 | (1984-85 to 1991-92) 101? men, and 131? women | Total cancer risk | Fruit (not defined) |
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Age, smoking and socioeconomic group. |
9) Strandhagen E. (2000) | The Study Of Men Born In 1913. | 730 men aged 54. | (Sweden) 26 | (1967-1993) 226 | Cancer disease | Fruit (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. | 9,959 men and women aged 15-99. | (Finland) 24 | (1967-1991) 997? | All cancer risk | Fruits other than apples | RR = 0.90 (0.71-1.14; No P-value) for the highest vs lowest quartile of consumption (not defined). | (For apples, also no association was found: RR = 0.87 (0.72-1.04; 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 | Fruits (Cantaloupe, mangos, watermelon, apricots, nectarines [including apricot nectar], peaches, papayas, persimmons, sour cherries, prunes, prune juice, apples, applesauce [not apple juice], bananas, avocados, guacamole, pineapple, pineapple juice, blackberries, blueberries, raspberries, boysenberries, loganberries, sweet cherries, fruit cocktail, oranges, tangerines, mandarin oranges, orange juice, white grapefruit and juice, pink/red grapefruit and juice, honeydew, casaba melons, strawberries, cranberry juice cocktail, plums, rhubarb, grapes, pears, figs, raisins, dates) |
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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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