Abstract

BACKGROUND: In 2007, the WCRF published a systematic review with information about a large amount of life style variables in relation to a large variety of cancer types (1). The WCRF concluded that there was a) limited evidence suggesting that non-starchy vegetables, or fruits protect against colorectal cancer, and b) garlic probably protects against colorectal cancer.
OBJECTIVES:

• To review all prospective studies which provided data about total fruits or vegetables, their subgroups, and specific types of vegetables and fruits, in relation with colon-, rectal-, and total colorectal cancer risk, disease progression and mortality/survival.
• To define the amount of consumption found to be related with the described effects on cancer.
• To define possible effect modification by confounders.

DATA SOURCE: The Pubmed database was searched (No start date - Sep 11, 2009) for relevant articles using the keywords "cancer, neoplasm, or neoplasms" combined with "vegetables, vegetable, fruit, or fruits" and a fair amount of other keywords. The exact search term is described in the methods.
Prospective studies published in the English language were included. Reference lists were searched for additional articles.
RESULTS: 51 articles were found which provided information about 32 different cohorts.
Of these, 0 articles needed to be excluded because of language restrictions. And no articles were excluded because of any other reasons.
Results are described when any evidence for an association - as defined in the Methods - was found. In addition, data about total vegetables or fruits is described.

• Total colon cancer risk.
  -Data about the relation with total vegetables was provided by a pooled analysis of 14 cohorts and 6 additional cohorts. No evidence was found for an association between total vegetables and total colon cancer risk. Except for suggestive evidence for a protective effect among men at an intermediate level of consumption (mean 336 g/day).
  -Data about the relation with total fruit was provided by a pooled analysis of 14 cohorts and 6 additional cohorts. Total fruit probably protects against total colon cancer risk. This evidence was restricted to women. Protective effects were found at the level of consumption of 100- < 300 g/day and ≥ 400 g/day.
  -Bananas possibly protect against total colon cancer risk at the level of consumption of ≥ 1 banana/week. Suggestive evidence for a protective association was found with lower consumption.
  -Spinach possibly protects against total colon cancer risk at the level of consumption of ≥ 1 serving/week (One serving = 1/2 cup). Suggestive evidence for a protective association was found with lower consumption.
  -Prunes possibly increase total colon cancer risk. No level of consumption could be defined for the association.
  -Possible protective effects against total colon cancer risk were found of intermediate (but not high) levels of consumption of the following items: peas/lima beans (> 0 to < 1 serving/wk. One serving = 1/2 cup/beans), broccoli (> 0 to < 1 serving/wk. One serving = 1/2 cup), tomatoes/tomato juice (1 tomato week to < 0.5 tomato/day), and Brussels sprouts (> 0 to < 1 serving/wk. One serving = 1/2 cup).
• Distal colon cancer risk.
  -High vs low vegetable consumption possibly protects against distal colon cancer risk among both sexes (≥ 200 g/day). Probable evidence for a protective effect was found at the level of consumption of 200- < 300 g/day among men.
  -Total fruit possibly protects against distal colon cancer risk among women. This effect was found at the level of consumption of ≥ 400 g/day.
  -Items from the umbelliferae family possibly protect against distal colon cancer risk, but no evidence was found for an association with total colon cancer.
• Proximal colon cancer risk.
  -No evidence was found for an association between total vegetables and proximal cancer risk.
  -Total fruit possibly protects against proximal colon cancer risk among women at the level of consumption of 200- < 300 g/day.
• Rectal cancer risk.
  -Data about the relation with total vegetables was provided by 9 cohort studies. No evidence was found for an association between total vegetables and rectal cancer risk.
  -Data about the relation with total fruits was provided by 9 cohort studies. No evidence was found for an association between total fruit and rectal cancer risk.
• Effect modification:
  Possible effect modification by confounders was reviewed. No evidence was found for modifying effects on the relation between total fruits or vegetables and colon or rectal cancer risk.
• Advanced stage/metastatic disease risk or disease progression.
  No data was found about the relation with advanced/metastatic disease or disease progression.
• Mortality risk.
  -Data about the relation between total vegetables and colon cancer mortality was provided by 2 cohorts. No evidence was found for an association.
  -Data about the relation between total fruits and colon, rectal, and colorectal cancer mortality was provided by 6 cohorts. No evidence was found for an association.

CONCLUSION: Among women, total fruit possibly protects against distal, proximal and total colon cancer risk at different levels of consumption. For total colon cancer, this effect was found at the level of consumption of both 100- < 300 g/day, and ≥ 400 g/day. Among men, suggestive evidence was found for a protective effect of total vegetables against total colon cancer risk at an intermediate level of consumption (median of ranges: 336 g/day). For both sexes combined, high vs low vegetables consumption (≥ 200 g/day) possibly protects against distal colon cancer risk. But probable evidence for a protective effect was found at the level of consumption of 200- < 300 g/day among men. No other associations of total fruits or vegetables were found with any cancer end point and no evidence was found for effect modification by possible confounders.
High vs low consumption of bananas (≥ 1 banana/wk) and spinach (≥ 1 serving/wk. One serving = 1/2 cup) possibly protect against total colon cancer risk. Suggestive evidence of a protective effect was found for lower levels of consumption of both items. Suggestive evidence was found of a protective effect of total soy foods (but not tofu, or soybean paste soup) with cancer risk, but results were inconsistent and confined to research from Asian populations. Prunes possibly increase total colon cancer risk, but the level of consumption for this association could not be defined.
Possible protective effects against total colon cancer risk were found of intermediate (but not high) levels of consumption of the following items: peas/lima beans (> 0 to < 1 serving/wk. One serving = 1/2 cup/beans), broccoli (> 0 to < 1 serving/wk. One serving = 1/2 cup), tomatoes/tomato juice (1 tomato week to < 0.5 tomato/day), and Brussels sprouts (> 0 to < 1 serving/wk. One serving = 1/2 cup).
No evidence was found for any association with rectal cancer.

REFERENCE:
1) World Cancer Research Fund / American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington DC: AICR, 2007. Full text

Total vegetables and total colon cancer risk.

Data about the relation between total vegetables and total colon cancer risk was provided by a pooled analysis of 14 cohorts and 6 additional cohorts, including a total of > 9,847 cases (the amount of cases was not defined in one cohort of very large size [27]).
A significant protective trend among men, but not women, was found in one cohort including 734 male cases (30). And a nonsignificant trend of a protective effect among women, but not men, was found in one small cohort including 105 female cases (1). No other (non)significant associations were found.

Inclusion of intermediate levels of consumption:
Among men, (non)significant protective effects were found in the 2nd-5th quintile of consumption (median 212 - median 539 g/d) in one cohort of very large size (Park Y). And a significant protective effect was found in the 3rd quintile of consumption (median 336 g/d) in another cohort of very large size (Nomura AM).
Among women, no (non)significant associations were found at any level of consumption in any cohort.

Conclusion: Few effects were seen. No evidence was found for an association between total vegetables and total colon cancer risk. But among men, a protective effect at an intermediate levels of consumption is suggested (median intake 336 g/day). Lack of specific data about amounts of cases prevents indication of the level of evidence, but this evidence probably is suggestive.

Total vegetables and distal colon cancer risk.

Data about the relation between total vegetables and distal colon cancer risk was provided by a pooled analysis of 14 cohorts, and two additional cohorts.
A significant protective effect was found in the pooled analysis (29) including 756,217 subjects: RR = 0.82 (0.68-0.98; P = 0.01). Stratified by sex, the strength of the associaton did not change, but the trend became nonsignificant among both men and women. A significant protective effect among men, but not women was found in another cohort (27). No association was found in the remaining cohort (18).

Inclusion of intermediate levels of consumption:
Among men, a strong significant protective effect was found at the level of 200- < 300 g/day in the pooled analysis (Koushik A). In addition, significant protective effects were found at the 2 lower-peak levels of consumption (median 270, and median 540 g/day) in a cohort of very large size (Park Y).
Among women, also a significant protective effect was found at the consumption level of 200- < 300 g/day, but in the remainig cohort, resuls were not strengthened at this level of consumption.

Conclusion: A significant protective effect of high vs low consumption (≥ 200 g/day) was found in a pooled analysis, but the trend became nonsignificant when stratified by sex. In addition, a significant protective effect of high vs low consumption was also found in cohort of very large size, but this effect was restricted to men only. High vs low vegetable consumption possibly protects against distal colon cancer risk among both sexes.
A significant protective effect of an intermediate level of consumption (200-< 300 g/day) was found among both men and women, which remained significant when stratified by sex. Among men, this effect was strengthened by results from one cohort of very large size, in which a significant protective effect was found at this level of consumption. Vegetables probably protect against distal colon cancer risk among men at the level of 200-< 300 g/day.

Total vegetables and proximal colon cancer risk.

Data about the relation between total vegetables and proximal colon cancer risk was provided by a pooled analysis of 14 cohorts, and two additional cohorts. No associations were found.

Inclusion of intermediate levels of consumption:
Among men, a significant protective effect was found in the 3rd quintile of consumption (median intake 270 g/day) in one cohort of very large size (Park Y). No other associations were found. Clearly, no consistent level of consumption was found for any effect in both sexes:

Conclusion: No associations were found. No evidence was found for an association between total vegetables and proximal cancer risk.

Total vegetables and rectal cancer risk.

Data about the relation between total vegetables and rectal cancer risk was provided by 9 cohort studies.
A nonsignificant trend of an increased risk among women, but not men was found in one cohort (9). No other associations were found.

Inclusion of intermediate levels of consumption:
Among both men and women, no (non)significant effects were found at any level of consumption:

Conclusion: A nonsignificant trend of an increased risk among women was found in one cohort. No other associations were found. No evidence was found for an association between total vegetables and rectal cancer risk.

Total vegetables and total colorectal cancer risk.

Primary variables of interest were colon cancer, or rectal cancer. But results from articles about some cohorts were not stratified by cancer site (colon + rectal), and only show associations with total colorectal cancer risk.
The association with total colorectal cancer risk is not discussed, but findings are presented in the following table: Click.

Total fruit and total colon cancer risk.

Data about the relation between total fruit and total colon cancer risk was provided by a pooled analysis of 14 cohorts (29) and 6 additional cohorts, including a total of > 9,794 cases (the amount of cases was not defined in one cohort of very large size [27]).

A significant protective effect was found in the pooled analysis (RR = 0.87 [0.77-0.97; P = 0.04]), and in one additional cohort of small size among women (1) including a total of 5,897 cases (< 60% of all cases). In addition, a nonsignificant protective effect was found in one cohort of very large size (18) including a total of 1,828 cases (< 19% of all cases).
Stratified by gender, results from the pooled analysis were restricted to women, and the trend became nonsignificant.

Inclusion of intermediate levels of consumption:
Among women, significant protective effects were found at different levels of consumption (100- < 300 g/day, and ≥ 400 g/dag) in the pooled analysis (Koushik A). In addition, a significant protective effect was found at the level of consumption of > 246 g/day in one additional cohort of small size (Shibata A). No associations were found among men:

Conclusion: A significant protective effect was found in a pooled analysis of 14 cohorts, and one additional cohort including 60% of all cases. And a protective effect was found in one cohort of very large size, but this effect was nonsignificant. Total fruit possibly protects against total colon cancer risk. This evidence was restricted to women. Protective effects were found at the level of consumption of 100- < 300 g/day and ≥ 400 g/day.

Total fruit and distal colon cancer risk.

Data about the relation between total fruit and distal colon cancer risk was provided by a pooled analysis of 14 cohorts, and two additional cohorts.
A significant protective effect among women, but not men, was found in the pooled analysis (12 cohorts for women) at the level of consumption of ≥ 400 g/day (29). In addition, a nonsignificant trend of a protective was found in one cohort of very large size, but results were not stratified by gender (18). No association was found in the remaining cohort of very large size (27).

Inclusion of intermediate levels of consumption:
No other (non)significant effects were found at any level of consumption.

Conclusion: A significant protective effect among women was found in a pooled analysis of 12 cohorts, but no significant effects were found in any of the cohorts of very large size. Total fruit possibly protects against distal colon cancer risk among women. This effect was found at the level of consumption of ≥ 400 g/day.

Total fruit and proximal colon cancer risk.

Data about the relation between total fruit and proximal colon cancer risk was provided by a pooled analysis of 14 cohorts, and two additional cohorts. No (non)significant associations were found in any cohort.

Inclusion of intermediate levels of consumption:
A significant protective effect at an intermediate level of consumption (200- < 300 g/day) was found among women in the pooled analysis (12 cohorts for women). No other associations were found among men or women.

Conclusion: A significant protective effect of an intermediate level of fruit consumption was found among women in a pooled analysis of 12 cohorts. No other associations were found. Total fruit possibly protects against proximal colon cancer risk among women at the level of consumption of 200- < 300 g/day.

Total fruit and rectal cancer risk.

Data about the relation between total fruits and rectal cancer risk was provided by 9 cohort studies.
Women: A significant protective effect was found in one cohort examining women only (15), but a significantly increased risk was found in one other cohort among women, but not men (27). No other associations were found (6, 9, 24, 25, 30).
Men: No associations were found.

Inclusion of intermediate levels of consumption:
Some significant effects were found at intermediate levels of consumption, but clearly no consistent associations were found:

Conclusion: Inconsistent findings were done among women only, but no evidence was found for an association between total fruit and rectal cancer risk.

Total fruits and total colorectal cancer risk.

Primary variables of interest were colon cancer, or rectal cancer. But results from articles about some cohorts were not stratified by cancer site (colon + rectal), and only show associations with total colorectal cancer risk.
The association with total colorectal cancer risk is not discussed, but findings are presented in the following table: Click.

Colorectal cancer mortality.

Data about cancer mortality is reviewed. Total fruits or total vegetables consumption in relation to total-, distal-, or proximal colon, rectal cancer, and total colorectal cancer mortality is discussed. Data about cancer mortality is added to the related tables of cancer risk on this page.

1) Total vegetables:
Data about total vegetables in relation to colon cancer mortality was provided by 2 cohorts. A significant protective effect was found among women, but not men, in the largest cohort (7). No significant association with colon cancer + total colorectal cancer mortality was found in the other cohort (12). No other data was found.
2) Total fruits:
Colon cancer: Data about total fruits in relation to colon cancer mortality was provided by 2 cohorts. A significantly increased risk among women, but not men was found in one cohort (22). A significant trend of an increased risk was also found in the other cohort, examining men only (12).
Rectal cancer: Data about total fruits in relation to rectal cancer mortality was provided by 1 cohort (22). No association was found among men or women.
Colorectal cancer: Data about total fruits in relation to total colorectal cancer mortality was provided by 4 cohorts (2, 10, 19, 21). No associations were found.

Conclusion: Few associations were seen among cohorts. No evidence was found for an association between total fruits or total vegetables and colorectal cancer mortality.

Advanced stage/metastatic disease risk.

No data about the relation between fruits or vegetables and advanced stage and/or metastatic disease risk is provided by any article about any of the cohorts.

Possible effect modification by confounders.

Data about possible effect modification is reviewed. Modifying effects on the relation between total fruits or total vegetables and total-, distal-, or proximal colon, and rectal cancer risk are discussed. Effects are discussed when found in any number of cohorts.

1) Total vegetables

• BMI: Data about effect modification by BMI was provided by 3 cohorts. In one cohort, a decreased risk of total-, proximal-, or distal colon, and rectal cancer from vegetable consumption was most apparent among individuals in the highest tertile of BMI (18). No effect modification with total colon (15, 25), or rectal cancer (15, 25) was found in the remaining cohorts.
• Smoking status: Data about effect modification by smoking status was provided by 5 cohorts. In one cohort, a significantly increased rectal cancer risk of vegetable consumption was found among current smokers, while no association was found among never, and former smokers (18). In the same cohort, a significantly decreased colon cancer risk of vegetable consumption was found among former smokers, while no association was found among never, and current smokers. No effect modification with colon (6, 7, 25), or rectal (25) cancer was found in the remaining cohorts.
• A family history of cancer: Data about effect modification by a family history of cancer was provided by 3 cohorts. In one cohort, a nonsignificantly increased colon cancer risk of vegetable consumption was found among women with a positive family history of colon cancer, while no association was found among women without a family history (8). No effect modification with colon cancer by a family history of colorectal cancer was found in the remaining cohorts (6).
• Other: No other effect modification was found in any other cohort.

2) Total fruits:

• Meat consumption: Data about effect modification by meat consumption was provided by 2 cohorts. In one cohort, a decreased risk of total-, proximal-, or distal, and rectal cancer from fruit consumption was most apparent among individuals in the highest tertile of red and processed meat consumption (18). No effect modification with total colon, or rectal cancer by meat, or fish was found in the remaining cohort (25).
• Smoking status: Data about effect modification by smoking status was provided by 5 cohorts. In one cohort, a nonsignificantly increased colon cancer risk of fruit consumption was found among male ever smokers, while no association was found among never smokers (6). No effect modification with colon (6 [women], 7, 18, 25), or rectal cancer (18, 25) was found in the remaining cohorts.
• Other: No other effect modification was found in any other cohort.

Conclusion: Effect modification was found by few potential confounders, and any effects were restricted to findings from one single cohort. No evidence was found for effect modification.