Whole-Grain Intake and Cancer: An Expanded Review and Meta-Analysis David R. Jacobs, Jr., Leonard Marquart, Joanne Slavin, Lawrence H. Kushi [Nutrition and Cancer 30(2):85-96, 1998. © 1998 Lawrence Erlbaum Associates, Inc.] Abstract Whole grains are nutrient rich and may protect against chronic disease. To study this, we previously reviewed 14 case-control studies of colorectal, gastric, and endometrial cancers and found consistently lower risk in those with high than in those with low whole-grain intake. Questions remained concerning other cancers, dietary assessment, quantity consumed, confounding, and differential study quality. Here we expand the review to 40 case-control studies of 20 cancers and colon polyps. Odds ratios are <1 for 46 of 51 mentions of whole-grain intake and for 43 of 45 after exclusion of 6 mentions with design/reporting flaws or low intake. The pooled odds ratio for high vs. low whole-grain intake among the 45 mentions was 0.66 (95% confidence interval = 0.60-0.72); they range from 0.59 to 0.78 across four types of dietary questionnaires. Odds ratios were <1 in 9 of 10 mentions of studies of colorectal cancers and polyps, 7 of 7 mentions of gastric and 6 of 6 mentions of other digestive tract cancers, 7 of 7 mentions of hormone-related cancers, 4 of 4 mentions of pancreatic cancer, and 10 of 11 mentions of 8 other cancers. Most pooled odds ratios for specific cancers were in the range of 0.5-0.8, notable exceptions being breast (0.86) and prostate (0.90). The pooled odds ratio was similar in studies that adjusted for few and many covariates. Dose-response associations were stronger in studies using food-frequency questionnaires than in more quantitative questionnaires. The case-control evidence is supportive of the hypothesis that whole-grain intake protects against various cancers. Introduction Consumption of phytochemical-rich plant foods, including whole grains, fruits, and vegetables, has been observed to be associated with reduced risk for certain cancers[1-4]. Whole grains, which contain micronutrients and nonnutrients lost in the refining process[5,6], may have health associations different from refined grains[4,5]. We previously reviewed 14 case-control studies of colorectal, gastric, and endometrial cancers and found reduced risk in high compared to low whole-grain intake in 18 of 21 mentions. Questions remained concerning the association of whole-grain intake with other cancers, the influence of disparate methods of dietary assessment in the various published studies, whether there is a dose-response relationship across increasing quantity consumed, the extent of residual confounding from related diet and life-style factors, and differential study quality. The purpose of this study is to expand the previous review and investigate the issues concerning that review as noted above. We include 40 case-control studies of 20 cancers and colon polyps. Selection of Studies for Review We used computerized bibliographic searches (i.e., Medline) and selected articles based on the occurrence in the title or abstract of "whole grain" or "whole meal" or "cancer"; we also systematically screened studies that mention "diet" and "cancer." We further searched for articles authored by any of the principal investigators of several groups who have published case-control studies of cancer. Additional articles were identified through a review of references for papers that were located. In addition to the 14 case-control studies[7-20] we previously reviewed[4], we have since located another 26 studies[21-46]. The studies were published between 1984 and 1997. This study was supported in part by General Mills, Inc. Address reprint requests to David R. 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