THESE INVESTIGATORS WANTED TO LEARN MORE ABOUT THE relationship between fruit and vegetable intake and cancer risk. To do this, they undertook a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort for the years between 1992 and 2000. The details of the EPIC study have been published; suffice it to say that it is a rigorous, large, impressive, meticulously done cohort study evaluating the effects of diet and other lifestyle factors on a variety of health outcomes. Because of the nature of the study, the investigators have access to fairly precise information about diet and lifestyle factors. For purposes of this study, they were able to correlate fruit and vegetable intake with cancer incidence and mortality, controlling for tobacco smoking and alcohol drinking. The initial cohort was 142,605 men and 335,873 women recruited from 23 European centers. There were significant variations among the centers in how the participants were recruited. For example, the French cohort drew from members of a health insurance plan, but participants at most of the Spanish and Italian centers included blood donors, members of several health insurance programs, employees of several enterprises, civil servants, and the general population. The cohorts of France, Norway, Utrecht, and Naples included only women. Data on diet of the participants for the preceding year were generally collected by country-specific, self-administered, food-frequency questionnaires, although there was variation in how this was done. The investigators evaluated associations between cancer and intake of total fruits, total vegetables, and total fruits and vegetables combined. Of note, potatoes, other tubers, legumes, and vegetable juices were not included in the calculation. Lifestyle questionnaires collected information on education, medical history, tobacco smoking, alcohol intake, occupational and leisure time physical activities, menstrual and reproductive history, use of oral contraceptives, and hormonal therapy. Height and weight were measured at the baseline examination. There were a variety of methods used to assess cancer incidence and mortality, but these data generally came from population-based registries, by contacting the study participants and next of kin, and by searches through health insurance records. Cancer incidence and mortality data were coded according to the ICD-10 and the second revision of the International Classification of Diseases for Oncology (ICDO-2). Nonmelanoma skin cancer was excluded from the analysis. For this study, smoking-associated cancers were considered to be cancers of the lung, kidney, upper GI tract, liver, stomach, pancreas, and bladder; alcohol-associated cancers included cancers of the upper GI tract, breast, liver, and colorectum. During a follow-up period of about 9 years, 9,604 men and 21,000 women were identified with cancer. The crude cancer incidence rates were 7.9 per 1,000 person-years in men and 7.1 per 1,000 person-years in women. Reduced cancer risk was statistically significantly associated with increased intake of fruits and vegetables combined, and also with total vegetable intake for the entire cohort (200 g/d increased intake of fruits and vegetables combined, hazard ratio [HR] = 0.97; 100 g/d increased intake of total vegetables, HR = 0.98). The reduction in cancer risk with intake of fruits alone showed a slightly weaker inverse association (100 g/d increased intake of total fruits, HR = 0.99). Stratification by alcohol intake suggested a stronger reduction (e.g., greater benefit with higher fruit and vegetable intake) in cancer risk in heavy drinkers; further, this analysis suggested that the reduction in cancer risk associated with intake for fruits and vegetables was greatest for cancers caused by smoking and alcohol. There appeared to be a "dose-response" relationship between fruit and vegetable intake and cancer risk; there was a decreased overall cancer risk for the second to the fifth quintiles of the distribution compared with the first quintile (P for trend < 0.001). Results were comparable in men and women, although the precision of the risk estimates was greater in women because of the larger number of cancers. There were variations in fruit and vegetable intake and in cancer risk among the centers. The median intake of fruits and vegetables was 335 g/d in the entire cohort. (This is roughly 4.5 servings per day. A "portion" of fruit or vegetables is about 80 g.) The intake ranged from a low of 231 g/day in Sweden to 511 g/day in Spain. In general, intake was higher in southern European countries than in northern European countries. High intake of fruits and vegetables was associated with female sex, higher education, physical activity, low alcohol intake, and never-smoking status. With regard to cancer risk, country-specific rates in men ranged from 3.8 per 1,000 personyears in the Netherlands to 10.1 per 1,000 person-years in Denmark. When countries were combined according to geographic region, the decrease in overall cancer risk for a 200 g/day increase in intake of fruits and vegetables was similar in the northern countries and in the southern countries. Since tobacco smoking and alcohol drinking are major causes of cancer, the investigators repeated the main analysis after stratification for these behaviors. Stratification by alcohol drinking suggested a stronger association in heavy drinkers than in moderate or nondrinkers. When cancers were stratified according to the presence of a causal association with tobacco smoking or alcohol drinking, the inverse association with higher intake of fruits and vegetables was restricted to cancers associated with smoking and drinking, and the duration of follow-up did not change the results. The authors concluded that there is a "very small inverse association between intake of total fruits and vegetables and cancer risk," and suggested that these results should be applied with caution. [ABSTRACT FROM AUTHOR]