Vegetables, Fruit, and prostate Cancer.

Abstract

OBJECTIVES:

  • To review all prospective studies which provided data about total fruits or vegetables, their subgroups, and specific types of vegetables and fruits, in relationship with prostate 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: 38 articles were found which provided information about 24 different cohorts. Of these, 0 articles were excluded.
Results are described when any evidence for an association - as defined in the Methods - was found. In addition, data about total vegetables or fruits, tomatoes, and soy is described. The 2 vegetable items were chosen because of a large amount of interest in the media.

Total prostate cancer risk.

  • Total vegetables: Data was provided by 11 cohorts, including 26,599 cases. No evidence was found for an association (RR = 0.98).
  • Total fruit: Data was provided by 16 cohorts, including 27,557 cases. No evidence was found for an association (RR = 1.03).
  • Tomatoes: No evidence was found for an association with tomatoes (8 cohorts), tomato sauce (3 cohorts), and tomato juice (4 cohorts) or the combined effect from all 3 categories.
  • Soy: Data about the relation with various soy foods was provided by 7 cohorts. No evidence was found for an association with total soy, tofu, and miso soup or the combined effect of all 3 categories.
  • Citrus fruit: Data was provided by 3 cohorts. Citrus fruit possibly increases prostate cancer risk among white men.
  • Legumes: Data was provided by 4 cohorts. Legumes possibly protect against prostate cancer risk at the level of consumption of > 71 g/day (RR = 0.86).

Advanced stage/metastatic disease risk or disease progression.

  • Total vegetables: Data about advanced prostate cancer risk was provided by 5 cohorts, including 4,188 cases. Findings were inconsistent, but no evidence was found for an association (RR = 1.08).
  • Total fruit: Data about advanced prostate cancer risk was provided by 5 cohorts, including 4,226 cases. No evidence was found for an association (RR = 0.95).
  • Tomatoes: Data about tomatoes was provided by 3 cohorts, and data about tomato sauce was provided by 2 cohorts. Though dose response results were found, no (non)significant effects between tomato sauce and advanced stage prostate cancer risk were found in any cohort. Inclusion of data about cooked tomatoes and high grade disease in the model, strengthens the possibility of a dose response effect, but does not strenghten the evidence. No evidence was found for an association between tomatoes and/or tomato sauce and advanced prostate cancer risk.
  • Soy: Data was provided by 5 cohorts. No evidence was found for an association.

Mortality risk.

  • Total vegetables: Data about prostate cancer mortality was provided by 4 cohorts, including 2,163 cases. Inconsistent findings were done, but no evidence was found for an association (RR = 0.85).
  • Total fruit: Data about prostate cancer mortality was provided by 4 cohorts of small size, including 456 cases. No evidence was found for an association (RR = 0.98).
  • Tomatoes: No evidence was found for an association with tomatoes (2 cohorts), or tomato sauce (1 cohort).
  • Soy: Data was provided by 2 cohorts. No evidence was found for an association.

Effect modification: Hardly any information is available about effect modification by possible confounders. No evidence was found for effect modification.

CONCLUSION: No evidence was found for an association between either total fruits or total vegetables and any examined end point: total cancer risk, advanced cancer risk, and cancer mortality. In addition, no evidence was found for an association when advanced cancer and mortality are considered as one single end point, or when advanced prostate cancer is stratified in disease stage and grade. No evidence was found for effect modification by confounders of any of these associations.
No evidence was found for an association between tomatoes, tomato juice, or tomato sauce and total- or advanced prostate cancer risk or mortality. The evidence did not change when all tomato categories were combined, or when advanced prostate cancer and mortality were grouped together.
No evidence was found for an association between any soy foods (total soy, tofu, miso soup, or a combination of these 3 items) and any cancer end point. But when advanced cancer risk and cancer mortality are considered one end point, miso soup possibly increases risk. The level of consumption for this effect could not be defined.
Citrus fruit possibly increases prostate cancer risk among white men. Legumes possibly protect against prostate cancer risk at daily consumption of > 71 g/day.


Total vegetables and prostate cancer.

Total prostate cancer risk: Data about total vegetables in relation to total prostate cancer risk was provided by 11 cohorts, including a total of 26,599 cases.
A protective association was found in the second (Wu K [7]), but not first (Giovannucci E [7]) part of follow-up of "The Health Professionals Follow-up Study". But no information is available about the strenght or significance of the association, and no adjustments were made for possible confounders. No other (non)significant associations were found. The average RR = 0.98 (excluding incomplete data from Tseng M [13], Wu K [7]).

Inclusion of intermediate levels of consumption:
A significantly increased risk was found in one cohort at the level of consumption of 140-193 g/day (Gonzalez A [21]). No other (non)significant associations were found at any level of consumption in any cohort.

RRs for the association between total vegetables and total prostate cancer risk (g/day):



Advanced stage prostate cancer risk: Data about total vegetables in relation to advanced prostate cancer risk was provided by 5 cohorts, including a total of 4,188 cases.
A significant protective effect against extraprostatic prostate cancer was found in one cohort, including 29,361 men in which the amount of cases is not defined (Kirsh VA [18]). But a significantly increased risk of advanced prostate cancer was found in one larger cohort, including 288,109 men and 1,778 cancer cases (George SM [24]). No other associations were found. The average RR = 1.08
Prostate cancer mortality: Data about total vegetables in relation to prostate cancer death was provided by 4 cohorts, including a total of 2,163 cases.
A signicantly increased risk of prostate cancer death was found in one cohort for low vs high consumption, but no specific amounts (servings/grams) of consumption were defined (Rodriguez C [9]). No other associations were found. The average RR = 0.85 (excluding incomplete data from Snowdon DA [1]).

Conclusion: Few associations were found. No evidence was found for an association between total vegetables and total prostate cancer risk at any level of consumption. Findings about the relation with advanced prostate cancer are contradictive, and no evidence was found for an association with advanced prostate cancer, or prostate cancer death. In addition, no evidence was found for an association when advanced cancer and mortality are considered as one single end point (RR = 1.00), or when advanced prostate cancer is stratified in disease stage and grade.

Prospective studies of total vegetables and total prostate cancer risk:
AuthorCohort nameCasesRelative Risk (RR)
24) George SM (2008)The NIH-AARP Diet and Health Study17,034RR = 0.97 (0.93-1.02; P = 0.106).
23) Ambrosini GL (2008)No cohort name97RR = 0.73 (0.38-1.40; P = 0.350).
21) Gonzalez A (2009)The VITAL Cohort761HR = 1.15 (0.93-1.42).
18) Kirsh VA (2007)The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial1,338RR = 0.88 (0.71-1.08; P = 0.24).
17) Stram DO (2006)The Multiethnic Cohort Study3,922RR = 1.00 (0.91-1.15; P = 0.466).
15) Key TJ (2004)The EPIC Study1,104RR = 1.00 (0.81-1.22; P = 0.738).
13) Tseng M (2004)The NHEFS Cohort136No association.
11) Chan JM (2000)The ATBC Study184RR = 0.8 (0.5-1.3; P = 0.84).
10) Schuurman AG (1998)The Netherlands Cohort Study606RR = 0.80 (0.57-1.12; P = 0.51).
7) Wu K (2004)The Health Professionals Follow-up Study (1993-1998)436Cases consumed less vegetables (no data).
7) Giovannucci E (1995)The Health Professionals Follow-up Study (1986-1992)773RR = 1.04 (0.81-1.34; P = 0.68).
2) Shibata A (1992)The Leisure World Study208RR = 1.04 (0.74-1.46).
Total number of cases: 26,599Average RR = 0.98


Prospective studies of total vegetables and advanced prostate cancer risk:
AuthorCohort nameCasesEnd pointRelative Risk (RR)
24) George SM (2008)The NIH-AARP Diet and Health Study1,778Advanced prostate cancerRR = 1.18 (1.01-1.38; P = 0.04).
18) Kirsh VA (2007)The Prostate, Lung, Colorectal and Ovarian Cancer Screening TrialAggressive: 520.
Extraprostatic: Not defined.
Aggressive or extraprostatic cancerAggressive cancer: RR = 0.81 (0.58-1.13; P = 0.27).

Extraprostatic cancer: RR = 0.41 (0.22-0.74; P = 0.01).
17) Stram DO (2006)The Multiethnic Cohort Study1,345Nonlocalized and high grade diseaseRR = 1.00 (0.90-1.10; P = 0.467).
10) Schuurman AG (1998)The Netherlands Cohort Study153Poorly- or undifferentiated prostate cancerRR = 0.99 (0.94-1.05).
7) Chan JM (2006)The Health Professionals Follow-up Study392Prostate cancer progressionRR = 1.26 (0.85-1.87).
Total number of cases: 4,188Average RR = 1.08


Prospective studies of total vegetables and prostate cancer mortality:
AuthorCohort nameCasesRelative Risk (RR)
22) Smit E (2007)The Puerto Rico Heart Health Progeam167OR = 1.61 (0.68-3.83; P = 0.48).
9) Rodriguez C (1997)The Cancer Prevention Study1,748RR = 1.26 (1.07-1.48) for low vs high consumption.
5) Hsing AW (1990)The Lutheran Brotherhood Cohort Study149RR = 0.7 (0.4-1.2).
1) Snowdon DA (1984)The Adventist Health Study99No association.
Total number of cases: 2,163Average RR = 0.85


Click here for an extended version of these tables.

Total fruit and prostate cancer.

Total prostate cancer risk: Data about total fruits in relation to total prostate cancer risk was provided by 16 cohorts, including a total of 27,557 cases. A significantly increased risk was found in one cohort, including 637 cases (Schuurman AG [10]). No other (non)significant associations were found. The average RR = 1.03 (excluding incomplete data from Kurahashi N [19], Tseng M [13], Wu K [7]).

Inclusion of intermediate levels of consumption:
Significantly increased risks were found at the levels of consumption of 151 g/day (Chan JM [11]), and 51-96 g/day (Gonzalez A [21]). Though the trend was significant, no (non)significant effects were found in one cohort (Schuurman AG [10]). No (non)significant protective effect was found at any level of consumption in any cohort.

RRs for the association between total fruit and total prostate cancer risk (g/day):



Advanced stage prostate cancer risk: Data about advanced prostate cancer risk was provided by 5 cohorts, including a total of 4,226 cases.
A significant protective effect was found in one cohort (Giovannucci E [7]). No other associations were found. The average RR = 0.95
Prostate cancer mortality: Data about total fruits in relation to prostate cancer death was provided by 4 cohorts of small size, including a total of 456 cases. No associations were found. The average RR = 0.98 (excluding incomplete data from Snowdon DA [1]).

Conclusion: Few associations were found with any end point. No evidence was found for an association between total fruits and total prostate cancer risk, advanced prostate cancer risk, or prostate cancer mortality. In addition, no evidence was found for an association when advanced cancer and mortality are considered as one single end point (RR = 0.95), or when advanced prostate cancer is stratified in disease stage and grade.

Prospective studies of total fruits and total prostate cancer risk:
AuthorCohort nameCasesRelative Risk (RR)
24) George SM (2008)The NIH-AARP Diet and Health Study17,034RR = 1.01 (0.95-1.06; P = 0.766).
23) Ambrosini GL (2008)No cohort name97RR = 0.94 (0.46-1.89; P = 0.848).
21) Gonzalez A (2007)The VITAL Cohort763HR = 1.19 (0.96-1.47).
19) Kurahashi N (2008)The JPHC Study201No association (P = 0.97).
18) Kirsh VA (2007)The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial1,338RR = 0.94 (0.77-1.15; P = 0.84).
17) Stram DO (2006)The Multiethnic Cohort Study3,922RR = 1.05 (0.94-1.16; P = 0.603).
15) Key TJ (2004)The EPIC Study1,104RR = 1.06 (0.84-1.34; P = 0.741).
14) Allen NE (2004)The Hiroshima/Nagasaki Life Span Study196RR = 1.20 (0.83-1.74; P = 0.40).
13) Tseng M (2004)The NHEFS Cohort136No association.
11) Chan JM (2000)The ATBC Study184RR = 1.3 (0.8-2.2; P = 0.13).
10) Schuurman AG (1998)The Netherlands Cohort Study637RR = 1.31 (0.96-1.79; P = 0.02).
7) Wu K (2004)The Health Professionals Follow-up Study (1993-1998)436No association.
7) Giovannucci E (1995)The Health Professionals Follow-up Study (1986-1992)773RR = 0.84 (0.59-1.84; P = 0.21).
6) Le Marchand L (1994)No cohort name198RR = 1.0 (0.7-1.6; P = 0.99).
3) Severson RK (1989)The Japan-Hawaii Study174RR = 1.57 (0.95-2.61).
2) Shibata A (1992)The Leisure World Study208RR = 1.04 (0.74-1.46).
1) Mills PK (1989)The Adventist Health Study156RR = 1.07 (0.72-1.58; P = 0.37).
Total number of cases: 27,557Average RR = 1.03


Prospective studies of total fruits and advanced prostate cancer risk:
AuthorCohort nameCasesEnd pointRelative Risk (RR)
24) George SM (2008)The NIH-AARP Diet and Health Study1,778Advanced prostate cancer riskRR = 0.98 (0.83-1.15; P = 0.91).
18) Kirsh VA (2007)The Prostate, Lung, Colorectal and Ovarian Cancer Screening TrialAggressive: 520.
Extraprostatic: Not defined.
Aggressive or extraprostatic cancerAggressive cancer: RR = 0.90 (0.65-1.25; P = 0.99).

Extraprostatic cancer: RR = 1.05 (0.61-1.83; P = 0.92).
17) Stram DO (2006)The Multiethnic Cohort Study1,345Non-localized or high grade diseaseRR = 1.01 (0.85-1.20; P = 0.769).
10) Schuurman AG (1998)The Netherlands Cohort Study160Poorly- or undifferentiated prostate cancerRR = 1.02 (0.99-1.06).
7) Giovannucci E (1998)The Health Professionals Follow-up Study423Advanced prostate cancer riskRR = 0.63 (0.43-0.93).
Total number of cases: 4,226Average RR = 0.95


Prospective studies of total fruits and prostate cancer mortality:
AuthorCohort nameCasesRelative Risk (RR)
22) Smit E (2007)The Puerto Rico Heart Health Program167OR = 1.13 (0.45-2.79; P = 0.30).
12) Appleby PN (2002)The Health Food Shoppers Study41RR = 0.66 (0.34-1.29).
5) Hsing AW (1990)The Lutheran Brotherhood Cohort Study149RR = 0.9 (0.6-1.4).
1) Snowdon DA (1984)The Adventist Health Study99No association.
Total number of cases: 456Average RR = 0.98


Click here for an extended version of these tables.

Possible effect modification by confounders.

Data about possible effect modification is reviewed. Modifying effects on the relation between total fruits or total vegetables and a) total prostate cancer risk, b) advanced prostate cancer risk, and c) prostate cancer death are discussed. All available data is discussed.

Total vegetables

  • Total prostate cancer risk: No effect modification of age or country was found (15).
  • Advanced prostate cancer risk: No effect modification of treatment groups and prognostic groups on prostate cancer progression was found (7).
    An increased risk of advanced prostate cancer was found in one cohort, but this association was weaker in never-smokers (24).
  • Prostate cancer mortality: No data available.

Total fruits

  • Total prostate cancer risk: No effect modification of age or country was found (15).
  • Advanced prostate cancer risk: No effect modification of treatment groups and prognostic groups on prostate cancer progression was found (7).
  • Prostate cancer mortality: No effect modification of smoking status was found (12).

Conclusion: Hardly any information is available about effect modification by possible confounders. No evidence was found for effect modification.