Fruit and Vegetable Intakes and Risk of Colorectal Cancer
Fruit and Vegetable Intakes and Risk of Colorectal Cancer
The authors examined the associations between fruit and vegetable intakes and risk of colorectal cancer in the NIH-AARP Diet and Health Study. Diet was assessed with a food frequency questionnaire at baseline. Relative risks and 95% confidence intervals were estimated by using the Cox proportional hazards model. During 5-year follow-up of 488,043 men and women aged 50-71 years, 2,972 incident colorectal cancer cases were identified. The respective 10th and 90th percentiles of total fruit and vegetable intake (servings/1,000 kcal per day) were 1.4 and 5.2 for men and 1.8 and 6.5 for women. Compared with that for the lowest quintile of vegetable intake, the multivariate relative risk for the highest quintile was 0.82 (95% confidence interval: 0.71, 0.94) for men and 1.12 (95% confidence interval: 0.90, 1.38) for women. Increased risk of colorectal cancer was observed for very low intake of total fruits and vegetables by men (multivariate relative risk for < 1 vs. ≥2.0 servings/1,000 kcal per day = 1.26, 95% confidence interval: 1.03, 1.54). Among subgroups of vegetables, green leafy vegetables were associated with a lower risk of colorectal cancer for men (multivariate relative risk for the highest quintile vs. the lowest = 0.86, 95% confidence interval: 0.74, 0.99). Intake of fruits was not related to risk of colorectal cancer in men or women.
Fruits and vegetables, rich in potentially anticarcinogenic constituents such as vitamin C, carotenoids, folate, dietary fiber, flavonoids, plant sterols, phenolic acids, and other phytochemicals, have been hypothesized to reduce risk of colorectal cancer. Animal and human feeding studies support the hypothesized protective effect of fruits and vegetables on cancer by providing plausible biologic mechanisms including reduction of oxidative damage to lipids and DNA, induction of phase I and II enzymes, and stimulation of DNA repair and apoptosis.
However, evidence from observational studies of fruit and vegetable intakes and risk of colorectal cancer has been inconsistent. The 1997 World Cancer Research Fund report, reviewing 22 case-control studies and four prospective cohort studies, concluded that convincing evidence of decreased risk of colorectal cancer existed for vegetable intake but not for fruit intake. In contrast, prospective cohort studies published after the World Cancer Research Fund report have generally found no associations or statistically nonsignificant, weak inverse associations of fruit, vegetable, and total fruit and vegetable intakes with risk of colorectal cancer. A recent review of 11 prospective cohort studies published through early 2003 found that fruit and vegetable intakes were not related to risk of colorectal cancer. Recently, the Women's Health Initiative Randomized Controlled Dietary Modification Trial reported that daily intake of at least five servings of fruits and vegetables along with a low-fat diet did not lower risk of colorectal cancer in postmenopausal women.
Although aggregate results from prospective cohort studies suggest no significant association between fruit and vegetable intakes and risk of colorectal cancer, the results should be carefully interpreted because of limitations in those studies. First, in the meta-analysis, considerable between-study heterogeneity was observed in the estimation of summarized relative risks but the sources of heterogeneity were not identified, suggesting that the summary of relative risks should be interpreted with caution. Second, null or statistically nonsignificant weak associations observed in most prospective cohort studies may be due to methodological limitations in observational studies. These cohort studies used a food frequency questionnaire (FFQ) that measured individuals' usual intakes of fruits and vegetables with error. The measurement error in intake estimation combined with errors from covariates modeled in multivariate models may attenuate true relative risks and lead to obscured null associations between intakes of fruits and vegetables and risk of colorectal cancer. Other potential limitations in cohort studies include limited ranges of fruit and vegetable intakes and relatively small numbers of cases in some studies, resulting in a lack of statistical power to detect a true modest association.
Two recent studies have suggested a possible threshold effect of fruit and vegetables on colorectal cancer; very low intakes of fruits and vegetables were associated with increased risk of colorectal cancer, but moderate to high intake did not lower this risk. Because our large cohort of men and women reported a wide range of fruit and vegetable intakes, we were able to investigate the associations of very low and high fruit and vegetable intakes with risk of colorectal cancer. In addition, we were able to examine specific subgroups of fruits and vegetables in relation to risk of colorectal cancer.
Abstract and Introduction
Abstract
The authors examined the associations between fruit and vegetable intakes and risk of colorectal cancer in the NIH-AARP Diet and Health Study. Diet was assessed with a food frequency questionnaire at baseline. Relative risks and 95% confidence intervals were estimated by using the Cox proportional hazards model. During 5-year follow-up of 488,043 men and women aged 50-71 years, 2,972 incident colorectal cancer cases were identified. The respective 10th and 90th percentiles of total fruit and vegetable intake (servings/1,000 kcal per day) were 1.4 and 5.2 for men and 1.8 and 6.5 for women. Compared with that for the lowest quintile of vegetable intake, the multivariate relative risk for the highest quintile was 0.82 (95% confidence interval: 0.71, 0.94) for men and 1.12 (95% confidence interval: 0.90, 1.38) for women. Increased risk of colorectal cancer was observed for very low intake of total fruits and vegetables by men (multivariate relative risk for < 1 vs. ≥2.0 servings/1,000 kcal per day = 1.26, 95% confidence interval: 1.03, 1.54). Among subgroups of vegetables, green leafy vegetables were associated with a lower risk of colorectal cancer for men (multivariate relative risk for the highest quintile vs. the lowest = 0.86, 95% confidence interval: 0.74, 0.99). Intake of fruits was not related to risk of colorectal cancer in men or women.
Introduction
Fruits and vegetables, rich in potentially anticarcinogenic constituents such as vitamin C, carotenoids, folate, dietary fiber, flavonoids, plant sterols, phenolic acids, and other phytochemicals, have been hypothesized to reduce risk of colorectal cancer. Animal and human feeding studies support the hypothesized protective effect of fruits and vegetables on cancer by providing plausible biologic mechanisms including reduction of oxidative damage to lipids and DNA, induction of phase I and II enzymes, and stimulation of DNA repair and apoptosis.
However, evidence from observational studies of fruit and vegetable intakes and risk of colorectal cancer has been inconsistent. The 1997 World Cancer Research Fund report, reviewing 22 case-control studies and four prospective cohort studies, concluded that convincing evidence of decreased risk of colorectal cancer existed for vegetable intake but not for fruit intake. In contrast, prospective cohort studies published after the World Cancer Research Fund report have generally found no associations or statistically nonsignificant, weak inverse associations of fruit, vegetable, and total fruit and vegetable intakes with risk of colorectal cancer. A recent review of 11 prospective cohort studies published through early 2003 found that fruit and vegetable intakes were not related to risk of colorectal cancer. Recently, the Women's Health Initiative Randomized Controlled Dietary Modification Trial reported that daily intake of at least five servings of fruits and vegetables along with a low-fat diet did not lower risk of colorectal cancer in postmenopausal women.
Although aggregate results from prospective cohort studies suggest no significant association between fruit and vegetable intakes and risk of colorectal cancer, the results should be carefully interpreted because of limitations in those studies. First, in the meta-analysis, considerable between-study heterogeneity was observed in the estimation of summarized relative risks but the sources of heterogeneity were not identified, suggesting that the summary of relative risks should be interpreted with caution. Second, null or statistically nonsignificant weak associations observed in most prospective cohort studies may be due to methodological limitations in observational studies. These cohort studies used a food frequency questionnaire (FFQ) that measured individuals' usual intakes of fruits and vegetables with error. The measurement error in intake estimation combined with errors from covariates modeled in multivariate models may attenuate true relative risks and lead to obscured null associations between intakes of fruits and vegetables and risk of colorectal cancer. Other potential limitations in cohort studies include limited ranges of fruit and vegetable intakes and relatively small numbers of cases in some studies, resulting in a lack of statistical power to detect a true modest association.
Two recent studies have suggested a possible threshold effect of fruit and vegetables on colorectal cancer; very low intakes of fruits and vegetables were associated with increased risk of colorectal cancer, but moderate to high intake did not lower this risk. Because our large cohort of men and women reported a wide range of fruit and vegetable intakes, we were able to investigate the associations of very low and high fruit and vegetable intakes with risk of colorectal cancer. In addition, we were able to examine specific subgroups of fruits and vegetables in relation to risk of colorectal cancer.
