NUTRITION AND CANCER, 58(1), 6–21 Copyright C  2007, Lawrence Erlbaum Associates, Inc. Fruits and Vegetables and Endometrial Cancer Risk: A Systematic Literature Review and Meta-Analysis Elisa V. Bandera, Lawrence H. Kushi, Dirk F. Moore, Dina M. Gifkins, and Marjorie L. McCullough Abstract: Endometrial cancer is the most common female gynecological cancer in the United States. Although obesity is a well-established risk factor, the role of other dietary factors is not well understood. The purpose of this study was to summarize and quantify the current evidence for fruit and vegetable intake and endometrial cancer by conducting a systematic literature review and meta-analysis. Searches were conducted to identify relevant papers published up to June 2006 in various databases. We included peer-reviewed manuscripts published in any language. Random and fixed- effects pooled risk estimates were estimated. We found one cohort study and 16 case-control studies evaluating various aspects of consumption. The random-effects summary esti- mates (95% CI) comparing high vs. low categories of intake reported were 0.71 (0.55–0.91) for total vegetables based on 10 studies, 0.85 (0.74–0.97) for cruciferous vegetables based on seven studies, and 0.90 (0.72–1.12) for total fruit based on 14 studies. For 100 g/day intake, summary ORs were 0.90 (0.86–0.95) for total vegetables, 0.79 (0.69–0.90) for cruciferous vegetables, and 0.97 (0.92–1.02) for total fruit. Excluding studies not meeting certain quality criteria provided similar results. The current evidence, based solely on case-control studies, with less than half being population- based, suggests a modest inverse association with vegetable consumption, particularly for cruciferous vegetables. We did not find any cohort studies evaluating fruit and vegetables separately. No firm conclusion can be drawn at this time in the absence of additional well-conducted population-based studies and, particularly, prospective data. INTRODUCTION Endometrial cancer accounts for about 4% of all cancers in women worldwide (1). It is the most common female gyne- cological cancer in the United States, ranking fourth among Elisa V. Bandera, Dirk F. Moore, and Dina M. Gifkins are affiliated with The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey; and School of Public Health, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey. Lawrence H. Kushi is affiliated with Division of Research, Kaiser Permanente, Oakland, California. Marjorie L. McCullough is affiliated with Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia. all cancers in women in age-adjusted incidence (2). Most of the major known risk factors for endometrial cancer have in common a prolonged and excessive exposure of the en- dometrium to estrogens unopposed by progesterone, such as estrogen replacement therapy (without progestin), sequential oral contraceptive formulations, a history of polycystic ovar- ian syndrome, and obesity (3). Reproductive factors have also been implicated, with studies indicating that late menopause, never having children, and infertility may increase risk (3). Although hypertension and diabetes have been reported as risk factors for endometrial cancer risk (3), their role, inde- pendent of obesity, is unclear. There is strong evidence of a relationship between obesity and endometrial cancer, partic- ularly for older women (4). In part because of the significant and well-established impact of obesity on endometrial cancer risk, there has been growing interest in the role that dietary factors may play on risk of this cancer. The role of fruits and vegetables on endometrial can- cer risk was reviewed in the WCRF/AICR 1997 Report (5). Based on a narrative review including data from five case- control studies, this report concluded that there was “pos- sible” evidence that consumption of vegetables and fruits decreased risk. A workgroup organized by the International Agency for Research on Cancer (IARC) evaluating the role of fruit and vegetable consumption on cancer prevention in- cluding data on seven case-control studies concluded in a report published in 2003 that the evidence for endometrial cancer was “weak at best” (6, 7). Commissioned by the WCRF, we conducted a sys- tematic and comprehensive literature review of the nutritional epidemiology of endometrial cancer starting in June 2003. The purpose of this review was to en- hance and update the previous 1997 review conducted for the First WCRF/AICR Report on Food, Nutrition, and the Prevention of Cancer (5). Our general methods followed the WCRF Specification Manual, available online (http://wcrf.org/research/research pdfs/slr manual 15.doc).