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A Pooled Analysis of Cohort Studies

Stephanie A. Smith-Warner, PhD; Donna Spiegelman, ScD; Shiaw-Shyuan Yaun, MPH; Hans-Olov Adami, MD; W. Lawrence Beeson, DrPH; Piet A. van den Brandt, PhD; Aaron R. Folsom, MD; Gary E. Fraser, MB, ChB; Jo L. Freudenheim, PhD; R. Alexandra Goldbohm, PhD; Saxon Graham, PhD; Anthony B. Miller, MB, BCh; John D. Potter, MB, BS; Thomas E. Rohan, MB, BS; Frank E. Speizer, MD; Paolo Toniolo, MD; Walter C. Willett, MD; Alicja Wolk, DSc; Anne Zeleniuch-Jacquotte, MD; David J. Hunter, MB, BS

JAMA. 2001;285:769-776.

Context  Some epidemiologic studies suggest that elevated fruit and vegetable consumption is associated with a reduced risk of breast cancer. However, most have been case-control studies in which recall and selection bias may influence the results. Additionally, publication bias may have influenced the literature on associations for specific fruit and vegetable subgroups.

Objective  To examine the association between breast cancer and total and specific fruit and vegetable group intakes using standardized exposure definitions.

Data Sources/Study Selection  Eight prospective studies that had at least 200 incident breast cancer cases, assessed usual dietary intake, and completed a validation study of the diet assessment method or a closely related instrument were included in these analyses.

Data Extraction  Using the primary data from each of the studies, we calculated study-specific relative risks (RRs) that were combined using a random-effects model.

Data Synthesis  The studies included 7377 incident invasive breast cancer cases occurring among 351 825 women whose diet was analyzed at baseline. For comparisons of the highest vs lowest quartiles of intake, weak, nonsignificant associations were observed for total fruits (pooled multivariate RR, 0.93; 95% confidence interval [CI], 0.86-1.00; P for trend = .08), total vegetables (RR, 0.96; 95% CI, 0.89-1.04; P for trend = .54), and total fruits and vegetables (RR, 0.93; 95% CI, 0.86-1.00; P for trend = .12). No additional benefit was apparent in comparisons of the highest and lowest deciles of intake. No associations were observed for green leafy vegetables, 8 botanical groups, and 17 specific fruits and vegetables.

Conclusion  These results suggest that fruit and vegetable consumption during adulthood is not significantly associated with reduced breast cancer risk.

Author Affiliations: Departments of Nutrition (Drs Smith-Warner and Willett and Ms Yaun), Epidemiology (Drs Spiegelman, Willett, and Hunter), Biostatistics (Dr Spiegelman), and Environmental Health (Dr Speizer), Harvard School of Public Health, Harvard Center for Cancer Prevention (Drs Willett and Hunter), Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (Drs Speizer, Willett, and Hunter), Boston, Mass; Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden (Drs Adami and Wolk); Center for Health Research, Loma Linda University School of Medicine, Loma Linda, Calif (Drs Beeson and Fraser); Department of Epidemiology, Maastricht University, Maastricht, the Netherlands (Dr van den Brandt); Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis (Dr Folsom); Department of Social and Preventive Medicine, State University of New York, Buffalo (Drs Freudenheim and Graham); Department of Epidemiology, TNO Nutrition and Food Research Institute, Zeist, the Netherlands (Dr Goldbohm); Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany (Dr Miller); Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Wash (Dr Potter); Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY (Dr Rohan); Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY (Dr Toniolo); and Nelson Institute of Environmental Medicine and Kaplan Cancer Center, New York University School of Medicine, New York (Dr Zeleniuch-Jacquotte).

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