Tomatoes and prostate cancer.

Introduction:
Data was categorized into 3 groups: tomato sauce, tomato juice, and tomatoes.

The category "tomato sauce" includes all items defined as tomato sauce/ketchup, as well as all items that include tomatoes from pizza.
The category "tomato juice" includes all items defined as tomato juice/V8 juice.
The category "tomatoes" includes all items defined as tomatoes (with or without a definition), as well as all items including tomatoes combined with tomato juice and/or sauce.

1) Tomatoes.

Total prostate cancer risk: Data about the relation between tomatoes and total prostate cancer risk was provided by 8 cohorts, including a total of 7,277 cases.
Significant protective effects of tomatoes were found in 2 cohorts, including 914 cases (1, 7). No other (non)significant associations were found in the remaining 6 cohorts (10, 13, 16-18, 23). The average RR = 0.98 (excluding incomplete data from Platz EA [16], Tseng M [13]).
Including results from intermediate levels of consumption:
In one cohort, a significant protective effect was found at the level of ≥ 2 servings/week (7; Giovannucci E). No other (non)significant asssociations were found at any level of consumption in any cohort.

RRs for the association between tomatoes and total prostate cancer risk (servings/wk):

-123 g of tomatoes (1 medium whole tomato) was calculated to 1 serving.

Advanced prostate cancer risk: Data about the relation with advanced prostate cancer risk was provided by 3 cohorts, including 2,257 cases. The average RR = 1.04.

A significantly increased prostate cancer progression risk of "fresh tomato products", and "fresh tomatoes" was found in one cohort (7).
A nonsignificant protective effect against non-localized/high grade prostate cancer risk of "cooked tomatoes" was found in another cohort (17).
No association with aggressive and extraprostatic cancer of "tomatoes" was found in the remaining cohort (18).

Prostate cancer mortality: Data about the relation with prostate cancer mortality was provided by 2 cohorts (5, 20). No associations were found with "tomatoes".

2) Tomato sauce.

Total prostate cancer risk: Data about the relation between tomato sauce and prostate cancer risk was provided by 3 cohorts, including a total of 4,779 cases.
A significant protective effect of tomato sauce was found in one cohort, including 3,544 cases (7). No associations were found with tomato sauce (18, 23), or ketchup (18) in the remaining cohorts. The average RR = 0.84.
Advanced stage prostate cancer risk: Data about the relation with advanced stage prostate cancer risk was provided by 2 cohorts (1,388 cases).
A significant protective effect of tomato sauce against advanced stage cancer, and metastatic cancer was found in "The Health Professional's Follow Up Study" (Giovannucci E. 2002 [7]). However, in a later publication about the same cohort, associations with advanced stage cancer lost significance, though the strenght of the association remained almost identical (Giovannucci E. 2007 [7]).
No association of spaghetti/tomato sauce with advanced prostate cancer was found in the other cohort, but risk gradually decreased with increasing units of consumption (Kirsh VA [18]).
Including results from intermediate levels of consumption:
Categorized data from The Health Professional's Follow Up Study (in > 2 units of consumption) was only available from the first publication (Giovannucci E. 2002 [7]). Clear dose responses can be seen:

RRs for the association between tomato sauce and advanced stage prostate cancer risk (servings/wk):

Prostate cancer mortality: Data about the relation with prostate cancer mortality was provided by one cohort (7). No association was found with tomato sauce.

3) Tomato juice.

Total prostate cancer risk: Data about the relation between tomato juice and prostate cancer risk was provided by 4 cohorts, including a total of 6,593 cases. No (non)significant association with any level of consumption was found in any cohort (7, 10, 17, 18). The average RR = 1.00.
Advanced prostate cancer risk: No data was found.
Prostate cancer mortality: No data was found.

Combined effects from cooked tomatoes and tomato sauce against advanced stage/high grade prostate cancer risk.

Dietary variables in the following tables are categorized according to definitions in the introduction. The item "cooked tomatoes" from one cohort includes 16 food items which are not all defined (Stram DO [17]). For this analysis, cooked tomatoes is grouped together with the items in the category "tomato sauce" (Giovannucci E [7], and Kirsh VA [18]).
Many epidemiologic studies combine cancers of advanced stage (3-4) at the time of diagnosis and those with high Gleason grade (gleason score ≥ 7/[very] poorly differentiated). Though the following analysis also combines these variables, it should be noted that a risk factor could influence the progression of a cancer independently of an effect on tumor grade.
Effects on high grade disease, rather than advanced stage disease were used from The Health Professional's Follow Up Study, because this allowed for a larger amount of cases in the analysis. This analysis shows some dose response effects, but in no cohort was a trend significant (P = 0.099, 0.31, and 0.20 for Stram DO, Kirsh VA, and Giovannucci E, respectively). Combined results showed the average RR = 0.85.

RRs for the association between cooked tomatoes/tomato sauce and advanced stage/high grade prostate cancer risk (servings/wk):

-120 g of cooked tomatoes (0.5 cup broiled from fresh tomatoes) was calculated to 1 serving.

Conclusion: Significant protective effects of tomatoes against total prostate cancer risk were found in 2 cohorts, but these cohorts included only 13% of all cases, and at no level of consumption is any association suggested. No evidence was found for an association between tomatoes and total prostate cancer risk. Few other associations were found. No evidence was found for an association between items in any of the categories and total prostate cancer risk or cancer mortality. This evidence did not change when items in the 3 different categories were grouped together.
Though dose response effects 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 did not strenghten the evidence. No evidence was found for an association between tomatoes, tomato juice, or tomato sauce and advanced prostate cancer risk. This evidence did not change when items in the 3 different categories were grouped together and/or when mortality was added to the model.

Perspective: Most (non)significant protective associations were found in one cohort: "The Health Professional's Follow-Up Study", and came from 4 different publications about this specific cohort, in which no association was found between tomato sauce and the most "relevant" outcome: fatal prostate cancer. More research is needed to clear up the relation between tomato sauce and disease progression, or cancer death.

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All prostate cancer:

Aggressive prostate cancer:

Extraprostatic cancer:

RR = 0.98 (0.80-1.20; P = 0.33) for the highest vs lowest quintile of consumption.

Amount specific data (servings per day):
0.3: RR = 1.
0.5: RR = 1.16 (0.97-1.38).
0.7: RR = 1.14 (0.95-1.37).
1.0: RR = 1.04 (0.86-1.26).
1.5: RR = 0.98 (0.80-1.20).

RR = 1.12 (0.82-1.54; P = 0.91) for the highest vs lowest quintile of consumption.

Amount specific data (servings per day):
0.3: RR = 1.
0.5: RR = 1.27 (0.97-1.67).
0.7: RR = 1.13 (0.85-1.51).
1.0: RR = 0.97 (0.72-1.32).
1.5: RR = 1.12 (0.82-1.54).

RR = 0.86 (0.50-1.47; P = 0.31) for the highest vs lowest quintile of consumption.

Amount specific data (servings per day):
0.3: RR = 1.
0.5: RR = 1.19 (0.77-1.84).
0.7: RR = 1.09 (0.69-1.72).
1.0: RR = 0.91 (0.55-1.49).
1.5: RR = 0.86 (0.50-1.47).

Total tomato servings:

Raw tomatoes:

Canned tomatoes:

RR = 0.99 (0.81-1.21; P = 0.36) for the highest vs lowest quintile of consumption.

Amount specific data (servings/d):
0.33: RR = 1.
0.53: RR = 1.16 (0.97-1.38).
0.72: RR = 1.05 (0.87-1.26).
0.97: RR = 1.05 (0.87-1.26).
1.47: RR = 0.99 (0.81-1.21).

RR = 1.04 (0.86-1.27; P = 0.84) for the highest vs lowest quintile of consumption.

Amount specific data (servings):
< 2.5/mo: RR = 1.
2.5/mo to 1/wk: RR = 1.10 (0.90-1.34).
> 1 to 2/wk: RR = 1.08 (0.90-1.30).
> 2 to 3/wk: RR = 0.98 (0.80-1.21).
> 3/wk: RR = 1.04 (0.86-1.27).

RR = 0.96 (0.79-1.16; P = 0.50) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/mo: RR = 1.
1-3/mo: RR = 1.08 (0.95-1.22).
1/wk: RR = 0.93 (0.78-1.12).
≥ 2/wk: RR = 0.96 (0.79-1.16).

Prostate cancer risk:

Tomatoes

Cooked tomatoes

Raw tomatoes

RR = 1.02 (0.92-1.14; P = 0.862) for the highest vs lowest quintile of consumption.

Amount specific data (g/1000 kcal):
≤ 12.0: RR = 1.
> 12.0-≤ 18.2: RR = 1.06 (0.96-1.18).
> 18.2-≤ 25.4: RR = 1.08 (0.98-1.20).
> 25.4-≤ 37.3: RR = 1.02 (0.92-1.14).
> 37.3: RR = 1.02 (0.92-1.14).

(P for heterogeneity by ethnic group = 0.275).

RR = 0.95 (0.85-1.06; P = 0.381) for the highest vs lowest quintile of consumption.

Amount specific data (g/1000 kcal):
≤ 20.5: RR = 1.
> 20.5-≤ 34.4: RR = 0.98 (0.89-1.09).
> 34.4-≤ 50.7: RR = 0.97 (0.88-1.08).
> 50.7-≤ 77.9: RR = 0.98 (0.88-1.09).
> 77.9: RR = 0.95 (0.85-1.06).

(P for heterogeneity by ethnic group = 0.111).

RR = 1.06 (0.96-1.18; P = 0.605) for the highest vs lowest quintile of consumption.

Amount specific data (g/1000 kcal):
≤ 1.9: RR = 1.
> 1.9-≤ 4.5: RR = 1.09 (0.98-1.20).
> 4.5-≤ 9.0: RR = 1.06 (0.95-1.17).
> 9.0-≤ 16.8: RR = 1.05 (0.95-1.17).
> 16.8: RR = 1.06 (0.96-1.18).

(P for heterogeneity by ethnic group = 0.360).

Total prostate cancer:

Ketchup

Spaghetti/tomato sauce

RR = 0.99 (0.82-1.19; P = 0.68) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/mo: RR = 1.
1-3/mo: RR = 1.04 (0.88-1.23).
1-2/wk: RR = 1.00 (0.85-1.19).
> 2/wk: RR = 0.99 (0.82-1.19).

RR = 0.96 (0.76-1.19; P = 0.65) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/mo: RR = 1.
1-3/mo: RR = 0.97 (0.81-1.16).
1/wk: RR = 0.90 (0.73-1.10).
≥ 2/wk: RR = 0.96 (0.76-1.19).

Spaghetti/tomato sauce.
Stratified by degree of disease progression at diagnosis:

Advanced prostate cancer (Stage III-IV or Gleason score ≥ 7)
(520 cases)

Nonadvanced prostate cancer (Stage I-II or Gleason score < 7)
(714 cases)

RR = 0.81 (0.57-1.16; P = 0.31) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/mo: RR = 1.
1-3/mo: RR = 0.88 (0.67-1.16).
1/wk: RR = 0.84 (0.61-1.16).
≥ 2/wk: RR = 0.81 (0.57-1.16).

Stage III-IV only:
When analyses were confined to high stage alone (stage III or IV, n = 189 cases), risks also tended to decrease with greater consumption of spaghetti/tomato sauce (RR, 0.73; 95% CI, 0.39-1.38 for the highest group; P = 0.35); however, no inverse associations were seen for any of the other variables (data not shown).

RR = 0.99 (0.73-1.35; P = 0.77) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/mo: RR = 1.
1-3/mo: RR = 1.03 (0.80-1.33).
1/wk: RR = 0.96 (0.72-1.28).
≥ 2/wk: RR = 0.99 (0.73-1.35).

Spaghetti/tomato sauce and total prostate cancer.
Stratified by family history of prostate cancer:

Family history of prostate cancer
(141 cases)

No family history of prostate cancer
(1197 cases)

RR = 0.68 (0.31-1.51; P = 0.12) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/mo: RR = 1.
1-3/mo: RR = 1.27 (0.71-2.27).
1/wk: RR = 1.15 (0.60-2.21).
≥ 2/wk: RR = 0.68 (0.31-1.51).

RR = 0.99 (0.79-1.25; P = 0.88) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/mo: RR = 1.
1-3/mo: RR = 0.94 (0.78-1.14).
1/wk: RR = 0.88 (0.71-1.09).
≥ 2/wk: RR = 0.99 (0.79-1.25).

Prostate cancer incidence
(3,544? cases):

Fatal prostate cancer
(312? cases):

RR = 0.80 (0.68-0.93; P = 0.01) for the highest vs lowest quartile of consumption.

Amount specific data (servings/week):
< 0.25: RR = 1.
0.25-1: RR = 0.93.
1-2: RR = 0.89.
> 2: RR = 0.80 (0.68-0.93).

RR = 0.91 (0.54-1.54; P = 0.67) for the highest vs lowest quartile of consumption.

Amount specific data (servings/week):
< 0.25: RR = 1.
0.25-1: RR = 1.16.
1-2: RR = 1.16.
> 2: RR = 0.91 (0.54-1.54).

Stratified by stage of prostate cancer:

Organ confined (T1 or T2 and NOMO)
(2,161 cases)

Minimally extraprostatic (T3a and NOMO)
(345 cases)

Advanced (T3b or T4 or N1 or M1)
(523 cases)

RR = 0.75 (0.61-0.92; P = ≤ 0.05) for the highest vs lowest quartile of consumption.

RR = 0.64 (0.37-1.10; No P-value) for the highest vs lowest quartile of consumption.

RR = 0.66 (0.44-1.00; P = 0.12) for the highest vs lowest quartile of consumption.

Stratified by disease grade:

Low grade (Gleason < 7)
(1,601? cases)

High grade (Gleason ≥ 7)
(1,110? cases)

RR = 0.66 (0.52-0.84; P = 0.003) for the highest vs lowest quartile of consumption.

Amount specific data (servings/week):
< 0.25: RR = 1.
0.25-1: RR = 0.82.
1-2: RR = 0.76.
> 2: RR = 0.66 (0.52-0.84).

RR = 0.86 (0.64-1.15; P = 0.20) for the highest vs lowest quartile of consumption.

Amount specific data (servings/week):
< 0.25: RR = 1.
0.25-1: RR = 0.95.
1-2: RR = 0.00.
> 2: RR = 0.86 (0.64-1.15).

Total prostate cancer:

Organ-confined

(no evidence of extraprostatic involvement):

Advanced

(with involvement of adjacent organs):

Metastatic

(including fatal cancers, and those with pelvic lymph node or distant metastasis):

Cumulative average updated RR = 0.77 (0.66-0.90; P = < 0.001) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/month: RR = 1.
1-3/month: RR = 0.96 (0.85-1.07).
1/week: RR = 0.80 (0.70-0.91).
≥ 2/week: RR = 0.77 (0.66-0.90).

This association did not change after additional adjustment for total fruit and vegetables (RR = 0.78; 95% CI = 0.66-0.91; P = < 0.001), or olive oil preference (RR = 0.77; 95% CI = 0.66-0.91; P = < 0.001).

RR = 0.72 (0.59-0.89; P = < 0.001) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/month: RR = 1.
1-3/month: RR = 0.86 (0.74-1.0).
1/week: RR = 0.63 (0.53-0.76).
≥ 2/week: RR = 0.72 (0.59-0.89).

RR = 0.65 (0.42-0.99; P = 0.02) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/month: RR = 1.
1-3/month: RR = 0.99 (0.75-1.31).
1/week: RR = 0.77 (0.55-1.08).
≥ 2/week: RR = 0.65 (0.42-0.99).

RR = 0.64 (0.39-1.05; P = 0.03) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/month: RR = 1.
1-3/month: RR = 1.06 (0.78-1.44).
1/week: RR = 0.77 (0.52-1.12).
≥ 2/week: RR = 0.64 (0.39-1.05).

Total prostate cancer. Stratified by age of diagnosis:

< 65 (807 cases)

≥ 65 (1674 cases)

RR = 0.89 (0.67-1.17; P = 0.20) for consumption ≥ 2 servings/week vs < 1 serving/month.

RR = 0.69 (0.56-0.84; P = 0.001) for consumption ≥ 2 servings/week vs < 1 serving/month.

The association did not strenghten with increasing age.

Total prostate cancer. Stratified by ancestry:

Southern European
(528 cases)

Other caucasian
(1474 cases)

RR = 0.66 (0.47-0.93; P = 0.002) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/month: RR = 1.
1-3/month: RR = 1.14 (0.87-1.49).
1/week: RR = 0.91 (0.68-1.23).
≥ 2/week: RR = 0.66 (0.47-0.93).

RR = 0.79 (0.65-0.98; P = 0.005) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
< 1/month: RR = 1.
1-3/month: RR = 0.90 (0.78-1.03).
1/week: RR = 0.77 (0.65-0.91).
≥ 2/week: RR = 0.79 (0.65-0.98).

**Prospective studies of tomato juice and prostate cancer:**
Author	Cohort name	Subjects	Years of follow-up	Cases	End point	Consumption of	Relative Risk (RR)	Adjustments
18) Kirsh VA (2006)	The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.	29,361 men aged 55-74. (USA)	Mean 4.2 (1993-2001 to 2001)	1338	Prostate cancer risk	Tomato and vegetable juice	RR = 1.02 (0.87-1.19; P = 0.89) for the highest vs lowest tertile of consumption. Amount specific data (servings): < 1/mo: RR = 1. 1-3/mo: RR = 1.03 (0.91-1.17). ≥ 1/wk: RR = 1.02 (0.87-1.19).	Age, total energy, race, study center, family history of prostate cancer, BMI, smoking status, physical activity, supplemental vitamin E intake, total fat intake, red meat intake, history of diabetes, aspirin use, and previous number of screening exams within the follow-up period.
17) Stram DO. (2006)	The multiethnic cohort study.	82,486 African-American, Japanese-American, Native-Hawaiian, Latino and White males aged 45-75. (USA)	1993-96 to 2001	3,922? (1,345 nonlocalized and high grade disease)	prostate cancer risk	Tomato/V8 Juice	RR = 0.95 (0.87-1.04; P = 0.247) for the highest vs lowest tertile of consumption. Amount specific data (g/1000 kcal): ≤ 0: RR = 1. > 0-≤ 5.3: RR = 0.95 (0.87-1.04). > 5.3: RR = 0.95 (0.87-1.04). (P for heterogeneity by ethnic group = 0.365).	age, BMI, education and family history of prostate cancer
10) Schuurman AG (1998)	The Netherlands Cohort Study.	58,279 men aged 55-69	6.3 ((1986-1992)	606?	prostate cancer risk	Tomato juice	No association: RR = 1.12 (0.96-1.29) per 25 g/day increment.	age, family history of prostate cancer, socioeconomic status and total fruit. Additionaly adjusted for total vegetables.
7) Giovannucci E (1995)	The Health Professionals Follow-Up Study.	47,894 men aged 40-75. (USA)	1986-1992	727	Non-stage A1 prostate cancer risk	Tomato juice	RR = 1.15 (0.90-1.49; P = 0.67) for the highest vs lowest quartile of consumption. Amount specific data (servings): 0: RR = 1. 1-3/mo: RR = 1.02 (0.86-1.21). 1/wk: RR = 0.85 (0.65-1.11). ≥ 2/wk: RR = 1.15 (0.90-1.49).	Age and energy.

Prospective studies of tomato juice and prostate cancer:

Author

Cohort name

Subjects

Years of follow-up

Cases

End point

Consumption of

Relative Risk (RR)

Adjustments

18) Kirsh VA (2006)

The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

29,361 men aged 55-74.
(USA)

Mean 4.2
(1993-2001 to 2001)

1338

Prostate cancer risk

Tomato and vegetable juice

RR = 1.02 (0.87-1.19; P = 0.89) for the highest vs lowest tertile of consumption.

Amount specific data (servings):
< 1/mo: RR = 1.
1-3/mo: RR = 1.03 (0.91-1.17).
≥ 1/wk: RR = 1.02 (0.87-1.19).

Age, total energy, race, study center, family history of prostate cancer, BMI, smoking status, physical activity, supplemental vitamin E intake, total fat intake, red meat intake, history of diabetes, aspirin use, and previous number of screening exams within the follow-up period.

17) Stram DO. (2006)

The multiethnic cohort study.

82,486 African-American, Japanese-American, Native-Hawaiian, Latino and White males aged 45-75.
(USA)

1993-96 to 2001

3,922?
(1,345 nonlocalized and high grade disease)

prostate cancer risk

Tomato/V8 Juice

RR = 0.95 (0.87-1.04; P = 0.247) for the highest vs lowest tertile of consumption.

Amount specific data (g/1000 kcal):
≤ 0: RR = 1.
> 0-≤ 5.3: RR = 0.95 (0.87-1.04).
> 5.3: RR = 0.95 (0.87-1.04).

(P for heterogeneity by ethnic group = 0.365).

age, BMI, education and family history of prostate cancer

10) Schuurman AG (1998)

The Netherlands Cohort Study.

58,279 men aged 55-69

6.3
((1986-1992)

606?

prostate cancer risk

Tomato juice

No association: RR = 1.12 (0.96-1.29) per 25 g/day increment.

age, family history of prostate cancer, socioeconomic status and total fruit.
Additionaly adjusted for total vegetables.

7) Giovannucci E (1995)

The Health Professionals Follow-Up Study.

47,894 men aged 40-75.
(USA)

1986-1992

727

Non-stage A1 prostate cancer risk

Tomato juice

RR = 1.15 (0.90-1.49; P = 0.67) for the highest vs lowest quartile of consumption.

Amount specific data (servings):
0: RR = 1.
1-3/mo: RR = 1.02 (0.86-1.21).
1/wk: RR = 0.85 (0.65-1.11).
≥ 2/wk: RR = 1.15 (0.90-1.49).

Age and energy.

Cancer & Diet. A systematic review.

Literature review.

Relating various aspects of our diet
to prostate cancer risk & mortality.

Tomatoes and prostate cancer.

Cancer & Diet. A systematic review.

Literature review.

Relating various aspects of our dietto prostate cancer risk & mortality.

Tomatoes and prostate cancer.

Relating various aspects of our diet
to prostate cancer risk & mortality.