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Mon, Jun 24, 2019

Cancer
The Health Benefits of Fruits and Vegetables



In the United States, 1 of every 4 deaths is attributed to cancer, totaling over 500,000 deaths per year (1). In the year 2001, 1,268,000 new cancer cases were anticipated. The National Institutes of Health estimated that overall costs for cancer were $180.2 billion in 2001 (1). The importance of dietary factors in the etiology of most cancers is well recognized and has been summarized in past reports including that of the American Institute for Cancer Research published in 1997 (2). Fruits and vegetables are among the most widely studied dietary risk factors for cancer (3). The current evidence is summarized in the following section according to the most common sites of cancer.


Cancer of the lung and bronchus is the leading cause of cancer death in men and women, with an estimated 157,400 deaths anticipated in 2001 (1). A variety of early reports showed an inverse relationship between fruit and vegetable intake and lung cancer and recent data support this association.


“… the current evidence collectively demonstrates that fruit and vegetable intake is associated with improved health, reduced risk of major diseases, and possibly delayed onset of age-related indicators.”


American women (Nurses' Health Study) in the highest quintile of fruit, vegetable, or combined fruit and vegetable intake had a 21-32% lower risk of lung cancer, with vegetable intake being statistically significant (4). Lung cancer risk was notably elevated among women consuming less than 2 servings of fruits and vegetables per day. The greatest protection was associated with intake of cruciferous vegetables (broccoli, cauliflower, brussel sprouts, cabbage), citrus fruits, and foods high in total carotenoids. Consistent with these data, strong inverse associations between intake of cruciferous vegetables and citrus fruits and lung cancer risk were reported in a cohort study in the Netherlands (5). Furthermore, prospective data from the American nurses (above) and men (in the Health Professionals' Follow-Up Study) showed an inverse association between lung cancer risk and intake of total carotenoids and ß-carotene (6), although fruit and vegetable intake was not associated with lung cancer risk in men.


Data from an ethnically diverse population in Hawaii showed a significant inverse association between lung cancer risk and consumption of foods rich in the flavonoid quercetin, including apples and onions (7). White grapefruit, an excellent source of the flavonoid naringen, was also protective. Total quercetin content of the diet tended to be associated with reduced risk although the effect was not significant.


The smoking status of an individual may be an important determinant of potential benefits associated with fruit and vegetable consumption. Recent data from a 25-year study of European men showed that fruit intake was associated with reduced risk of lung cancer, but the beneficial effect was limited to heavy smokers (8).
These results suggest that while not all studies of lung cancer and fruit and vegetable intake have shown statistically significant results, most prospective data suggest trends in the direction of a positive benefit. There is clearly a need for well-controlled intervention studies to further clarify the association between fruit and vegetable intake and lung cancer risk.


Breast cancer accounts for 31% of all cancer diagnoses and 15% of cancer deaths anticipated in females in 2001(1). Although dietary variables have been implicated in the development of breast cancer in case-control studies, a recent report that analyzed the collective data from 8 prospective trials found no association between intake of fruits and vegetables and reduced risk of breast cancer (9). Breast cancer risk was 3 to 9% lower in women in the highest decile of fruit or vegetable intake compared with the lowest decile but this reduction was not statistically significant.


Some studies including an analysis of specific subcategories of fruit and vegetable intake have shown that consumption of cruciferous vegetables might be protective against breast cancer. A recent case-control study found that cruciferous consumption (1-2 servings per day) reduced breast cancer risk by 40-50% in post-menopausal women (3, 10). Studies of biomarkers for breast cancer risk support a potential protective effect for cruciferous vegetables. In post-menopausal women, increasing daily intake of cruciferous vegetables from 9 grams to 193 grams (2 servings/day) resulted in a favorable shift in the ratio of urinary 2-hydroxysterone to 16-a hydroxysterone (11). These estrogen metabolites have been implicated as endocrine biomarkers for breast cancer. The average consumption of cruciferous vegetables in the United States is estimated to be 5-11 grams per day, well below the average intake in the above study (11). Thus, the available data seem to indicate a potential protective effect of some vegetables on risk of breast cancer. The association between breast cancer and total fruit and vegetable intake is less clear.


“… The average consumption of cruciferous vegetables in the United States is estimated to be 5-11 grams per day, well below the average intake in the above study (by Fowke, et al.)…Thus, the available data seem to indicate a potential protective effect of some vegetables on risk of breast cancer.”


Prostate cancer is the leading cancer diagnosis in men and accounts for 11% of anticipated deaths in males in 2001(1). There are very few studies linking fruit and vegetable intake with prostate cancer risk although a recent case-control study did show an inverse association between prostate cancer and intake of vegetables (35% reduced risk) and particularly cruciferous vegetables (41% reduced risk) (12). It has been suggested that lycopene, found mostly in tomatoes, may also be protective (3) although this finding has not been consistent. Clearly, further study is needed to determine the effect of cruciferous vegetables and tomatoes on risk of prostate cancer.


Cancers of the colon and rectum are equally distributed among men and women, accounting for approximately 10% of new cancer cases and 10% of expected cancer deaths in 2001(1). The majority of case-control studies published in the past showed an inverse association between fruit and vegetable consumption and colorectal cancer risk [reviewed in Steinmetz and Potter, 1996 (13)]. However, results from several recent prospective investigations have not consistently shown this effect.


The protective effects of fruits and vegetables on colorectal cancer risk might be less evident in study subjects who have a higher intake of these foods and/or regularly use a multiple-vitamin supplement (14). Terry et al. studied Swedish women with a wide range of fruit and vegetable intake over 9.6 years (14). They found an inverse association between colorectal cancer and total fruit and vegetable consumption, particularly among women who consumed very low amounts of fruits and vegetables. The authors concluded that increased fruit and vegetable consumption might be most beneficial for individuals who consume less than 2 servings of fruits and vegetables per day. In two large American cohorts of men and women, the majority of subjects consumed more than 2 servings of fruits and vegetables per day and over 30% used multiple vitamins. It is possible that these factors may have accounted, in part, for the lack of an association between fruit and vegetable intake and colon/rectal cancer incidence over a 10-16 year period (15).


Specific subsites of colorectal cancer may be affected by vegetable intake. In the Netherlands Cohort Study on Diet and Cancer vegetables, particularly cruciferous and cooked leafy vegetables, were more protective for distal than proximal colon cancers (16).


In summary, prospective studies have not provided conclusive evidence that fruit and vegetable consumption reduces risk of colorectal cancer (17). Clinical intervention studies are needed to provide additional data.


Non-Hodgkin's Lymphoma is the fifth leading cause of cancer death in men and sixth in women (1). There is limited evidence on the relationship between fruit and vegetable intake and risk of Non-Hodgkin's lymphoma but available studies suggest an inverse relationship. Data from 88,410 women enrolled in the Nurses' Health study showed that fruit and vegetable intake was associated with reduced risk of this cancer (18). The protective association was stronger for vegetables than for fruits. Consumption of 3 or more vegetable servings per day was associated with 38% lower risk compared to consumption of 1 or fewer vegetable servings per day. Women who consumed 3 or more servings/day of fruits had a 30% lower risk compared to women consuming 1 serving. A higher intake of cruciferous vegetables was specifically associated with a reduced risk. Women who consumed 5 or more servings of cruciferous vegetables had a 33% lower risk than women consuming 2 or fewer servings per week.


These data differs somewhat from an earlier case-control study that reported reduced risk of Non-Hodgkin's lymphoma associated with citrus fruit and dark green vegetable consumption in men, but not for women (3). Further research is needed to conclusively define the effects of fruit and vegetable intake on risk of Non-Hodgkin's lymphoma.


It was expected that ovarian cancer would be diagnosed in 23,400 women in the U.S., accounting for 4% of newly diagnosed cancers in 2001 (1). Recent case-control studies have reported a protective effect of fruits and vegetables on risk of this cancer. There was a 40% decrease in ovarian cancer incidence among women in the highest quartile of total fruit and vegetable intake (>164 grams/day) compared to women in the lowest quartile (<80 grams/day) (19). There was also reduced risk in women consuming higher amounts of dietary fiber, total vitamin A, total carotenoids, vitamin E, and ß-carotene.


A population based case-control study including pre- and post-menopausal women demonstrated that several micronutrients found in fruits and vegetables were associated with reduced risk of ovarian cancer (20). Total carotene, a-carotene, and ß-carotene intake were associated with significantly decreased risk in post-menopausal women and lycopene intake appeared to be protective in pre-menopausal women. Consistent with these observations, foods known to be rich sources of these nutrients were most clearly associated with decreased risk for ovarian cancer. Women consuming 2 or more servings (1/2 cup each) of tomato sauce per week had a 40% decrease in risk of ovarian cancer compared to women eating tomato sauce less than once a month. Women consuming 5 or more servings of raw carrots per week (4 cut sticks) had a 54% reduction in risk of ovarian cancer compared to women eating carrots less than once a month.
Although more study is needed, the available data are suggestive of an inverse relationship between fruit and vegetable consumption, particularly carotenoid rich sources, and risk of ovarian cancer.


Esophageal cancer was expected to account for 3% of all cancer deaths in American males in 2001(1). Until recently, squamous cell esophageal cancer was relatively rare in women, but rates have been on the rise in several countries over the past decade (21). Several newly published case-control studies support earlier data suggesting that fruit and vegetable consumption reduces risk of esophageal cancer. A recent composite analysis of case-control data from South America (22) and several case-control studies using populations in Uruguay, Italy, and Switzerland (21, 23, 24) have shown that intake of vegetables (cooked and raw), fruit, and combined fruits and vegetables is associated with reduced risk of carcinoma of the esophagus. Citrus fruit intake was associated with reduced incidence in the Italian population. Individuals with higher fruit and vegetable consumption (4-6 servings per day) have been shown to have 40-60% lower risk of esophageal cancer compared to those who consume 1-2 fruit and vegetable servings per day (3). In some studies the risk reduction remained significant after adjustment for antioxidant content, suggesting that other bioactive constituents in fruits and vegetables might account for the protective effect.


“… Citrus fruit intake was associated with reduced incidence (of esophageal cancer) in the Italian population. Individuals with higher fruit and vegetable consumption (4-6 servings per day) have been shown to have 40-60% lower risk of esophageal cancer compared to those who consume 1-2 fruit and vegetable servings per day.”


Thus, the bulk of evidence, although based primarily on case-control studies, suggests that consumption of vegetables and particularly fruits, reduces risk of squamous esophageal cancer. However, because the incidence of esophageal cancer is relatively low in affluent countries, there are no prospective data available regarding the association.


Cancers of the oral cavity were expected to account for 3% of all newly diagnosed cancers in U.S. males in 2001(1). Recent and past case-control studies have shown an inverse relationship between fruit and vegetable intake and cancers of the oral cavity, pharynx, and larynx (3, 13). In countries with a high prevalence of laryngeal cancer, raw vegetable intake was associated with the greatest reduction in risk (25). There was also a significant risk reduction with total fruit intake, and total fruit and vegetable intake, but not cooked vegetables. An analysis of several individual food items showed that tomatoes, lettuce, and oranges were associated with the strongest decrease in the risk of laryngeal cancer (65-68%), although several other fruits and vegetables also provided significant protection.


Bladder cancer was predicted to be the 9th leading cause of cancer death in men in 2001 (1). Two recent prospective trials and a meta-analysis provide general support for an inverse association between fruit and vegetable consumption and bladder cancer (26-28). In Japanese atomic-bomb survivors, consuming green-yellow vegetables several times a week (2-4 times every day) reduced risk of bladder cancer by 38-46% (26). There was a marginally significant protective effect for fruit as well. In an American cohort of male health professionals, intake of cruciferous vegetables was associated with reduced incidence of bladder cancer (28). These recent studies provide support for several earlier case-control studies showing that specific vegetables may be protective against the development of bladder cancer. However, studies of bladder cancer are confounded by the relatively low incidence rate.


Early case-control studies showed mixed results in relation to endometrial cancer risk and fruit and vegetable consumption (3). Several recent case-control studies have suggested a protective effect of consuming fruits, vegetables, or a combination of both although the association may be diminished after adjustment for body mass index (29). Reduced risk of endometrial cancer may be associated with intake of specific items including dark green/deep yellow fruits and vegetables (34% lower risk) and cruciferous vegetables (34% lower risk). Two other case-control studies showed an inverse association between endometrial cancer and vegetable, but not fruit, intake (30, 31).


Stomach cancer has been widely studied for dietary effects (3). The majority of case-control studies support a positive association between fruit and vegetable intake and reduced risk of stomach cancer (3). However, recent prospective trials have provided mixed results. In a 14-year follow-up study of 1.2 million men and women in the United States, there was no association between specific food groups and risk of stomach cancer (32). An overall diet pattern associated with increased intake of plant foods (sum of vegetables, citrus fruit, and whole grains) reduced risk by 21% in men (highest versus lowest textile), but this association was not evident in women. At least two European prospective studies have found no association between fruit and vegetable intake and stomach cancer while two others have noted an inverse effect (3). The reasons for this discrepancy are not clear and further study is needed to define the true effect of fruit and vegetable intake on risk of developing stomach cancer.


In conclusion, fruit and vegetable consumption is among the many factors that might influence the risk of developing cancer. Due to the complex etiology and the varied forms of different cancers, there are still many unresolved questions regarding the true association between fruit and vegetable intake and cancer risk. However, while the prospective studies are less convincing than the case-control studies, there are ample data to suggest that fruit and vegetable intake is likely to be protective for most cancers. Current investigations are beginning to move toward focusing on biomarkers of cancer risk and examination of plausible mechanisms by which fruit and vegetable intake might be protective. The ongoing work promises to provide important information to characterize the association between fruit and vegetable consumption and cancer.

 

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