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Plant foods and colon cancer Table 6. Association between colon cancer and fiber in the US multicentar study population All subjects < 67 years 67+ years Distal Proximal OR= (CI) OR= (CI) OR" (CI) OR" (CI) OR" (CI) Men (no. cases/controls) 1,099/1.290 542/645 557/645 542/1,290 526/1,290 Dietary fiber (g) < 17.2 1.0 w 1.0 ~ 1.0 w 1.0 Q 1.0 -- 17.3-22.3 0.9 (0.7-1.2) 0.9 (0.6-1.4) 0.8 (0.6-1.2) 0.8 (0.6.1.1) 1.0 (0.8-1.4) 22.4-27.5 0.9 (0.7-1,1) 0.9 (0.6-1.4) 0.8 (0.6-1.2) 0.8 (0.6-1.1) 0.9 (0.7-1.3) 27.6-34.5 0,9 (0,7-1.2) 0.9 (0.6-1.4) 0,9 (0.6-1,4) 0,9 (0.6-1.2) 1.0 (0.7-1,4) > 34.5 0,7 (0.5-1.0) 0.9 (0.6-1.5) 0.5 (0.3-0.9) 0.8 (0.5-1.3) 0.6 (0.4-1.0) P trend 0.16 0.34 0.10 0.56 0.10 Soluble fiber(g) <5.6 1.0 ~ 1.0 -- 1.0 ~ 1.0 ~ 1.0 -- 5.7-7.4 1.0 (0.8-1.3) 1.0 (0.7-1.5) 1.0 (0.7-1.4) 1.0 (0.7-1,4) 1.0 (0,7-1.4) 7.5-9.1 1,0 (0.7-1.3) 1.0 (0.7-1.5) 0.9 (0.6-1.3) 0.8 (0.6-1,2) 1.0 (0.7-1.4) 9.2-11.7 0,8 (0.6-1.1) 0.9 (0.6-1.4) 0.7 (0.5-1.1) 0.8 (0.6-1.1) 0.9 (0.7-1.3) > 11.7 0,8 (0.6-1.1) 1.0 (0.6-1.6) 0.6 (0.3-0.9) 0.9 (0.6-1.4) 0.6 (0.4-1.0) P trend 0.08 0.32 0.02 0.38 0.10 Insoluble fiber(g) < 11.0 1.0 w 1.0 Q 1.0 -- 1.0 w 1.0 w 11.1-14.4 0.9 (0.7-1.2) 1.0 (0.7-1.5) 0:8 (0.5-1.1) 0.8 (0.5-1.1) 1.0 (0.7-1.4) 14.5-17.8 0.8 (0.6-1.1) 0.9 (0.6.1.3) 0.8 (0.6-1.2) 0.8 (0.6-1.1) 0.9 (0.6-1.2) 17.9-22.5 1.0 (0.7-1.3) 1.0 (0.7-1.5) 0.9 (0.6-1.3) 1,0 (0.7-1.4) 0.9 (0.7-1.3) > 22.5 0.7 (0.5-1.0) 0.8 (0.5-1.3) 0.6 (0.4-0.9) 0.8 (0.5-1.2) 0.6 (0.4-1.0) P trend 0.16 0.34 0.14 0.66 0.08 Pectin (g) ~1.9 1.0 -- 1.0 ~ 1.0 -- 1.0 ~ 1.0 ~ 2.0-2.7 0.9 (0.7-1,.1) 0.7 (0.5-1.0) 1.0 (0.7-1.4) 0.8 (0.6-1.1) 0.9 (0.6-1.2) 2.8-3.5 0.9 (0.7-1.2) 0.9 (0.6-1.3) 0.9 (0.6-1.3) 0.9 (0.6-1.2) 1.0 (0.7-1.4) 3.6-4.7 0.8 (0.6-1.0) 0.7 (0.5-1.0) 0.9 (0.6-1.3) 0.7 (0.5-1.0) 0.8 (0.6-1.1) > 4.7 0.7 (0.5-0.9) 0.7 (0.5-1.1) 0.6 (0.5-0.9) 0.8 (0.6-1.2) 0.5 (0.4-0.8) P trend 0.02 0.36 0.02 0.20 0.02 Women (no. cases/controls) 89411120 4491543 446/577 429/1.120 446/1.120 Dietary fiber (g) ~ 14.5 1.0 ~ 1.0 -- 1.0 ~ 1.0 ~ 1.0 -- 14.6-18.9 1.1 (0.9-1.5) 1.3 (0.8-1.9) 1.1 (0.7-1.6) 1.2 (0.8-1.8) 1.1 (0.8-1.6) 19.0-23.3 0.8 (0.6-1.1) 0.9 (0.5-1.3) 0.8 (0.5-1.2) 1.0 (0.7-1.5) 0.7 (0.5-1.0) 23.4-30.3 0.9 (0.7-1.3) 1.0 (0.6-1,6) 0.9 (0.6-1.4) 1.1 (0.8-1.7) 0.8 (0.6-1.2) • 30.3 0.8 (0.5-1.1) 0.9 (0.5-1,5) 0.7 (0.4-1.2) 1.2 (0.8-1.9) 0.5 (0,3-0.9) P trend 0.12 0.42 0.18 0.62 0.02 Soluble fiber(g) ~4.8 1.0 -- 1.0 ~ 1.0 ~ 1.0 ~ 1.0 w 4.9-6.4 1.1 (0.8-1.4) 1.0 (0.7-1.6) 1.3 (0.6.1.8) 1.1 (0.7-1.5) 1.1 (0.8-1.6) 6.5-7.8 0.8 (0.6.1.1) 0,7 (0.4-1.0) 1.0 (0.7-1.6) 0.8 (0.6-1.2) 0.8 (0.5-1.2) 7.9-10.1, 0.9 (0.6.1.2) 0,8 (0.5-1.3) 1.0 (0.6.1.5) 1.0 (0.7-1.5) 0.8 (0.6-1.2) • 10.1 0.7 (0.5-1.1) 0,7 (0.4-1.2) 0.8 (0.6.1.4) 0.9 (0.6-1.4) 0,6 (0.4-1.0) P trend 0.06 0,10 0.40 0.60 0,02 Insoluble fiber (g) ~; 9.5 1.0 -- 1.0 -- 1.0 ~ 1.0 ~ 1.0 -- 9.6-12.2 1.0 (0.7-1.3) 1.1 (0.7-1.6) 0.9 (0.6-1.3) 1.0 (0.7-1.5) 0.9 (0.7-1.3) 12.3-15.0 0.8 (0.6-1.0) 0.7 (0.5-1.1) 0.8 (0.6-1.3) 0.9 (0.6-1.3) 0.7 (0.5-1.0) 15.1-19.8 0.8 (0.6.1.1) 1.0 (0.6-1.6) 0.7 (0.5-1.1) 1.0 (0.7-1.5) 0.7 (0.5-1.1) • 19.8 0.7 (0.5-0.9) 0.7 (0.4-1.1) 0.6 (0.4-1.1) 1.0 (0.6-1.6) 0.5 (0.3-0.7) P trend 0.02 0.18 0.08 0.98 < 0.01 Pectin (g) ~;1.8 1.0 ~ 1.0 -- 1.0 ~ 1,0 Q 1.0 -- 1.9-2,4 0.8 (0.6.1.1) 1.0 (0.6-1.4) 0.7 (0.5-1.0) 0.9 (0.6-1.3) 0.8 (0.5-1.1) 2.5-3.2 0.9 (0.7-1.2) 0.9 (0.6-1.3) 0.9 (0,6-1.4) 0.9 (0.6-1.2) 0.9 (0.7-1.3) 3.2-4,2 0.7 (0.5-1.0) 0.7 (0.5-1.1) 0.8 (0,5-1.1) 0.8 (0.6-1.2) 0.7 (0.5-I.0) > 4.2 0.8 (0.6-1.1) 0.8 (0.5-1.3) 0.8 (0,5-1.3) 1.0 (0.6-1.4) 0.7 (0.5-1.1) P trend 0.10 0.18 0.38 0.68 0.08 OR = odds ratio; CI = 95% confidence interval. Model adjusted for age. body mass index (wt/ht~ for men, wt/ht1"s for women). lifetime vigorous leisure time physical activity, use of aspirin/NSAIDs, presence or absence of a first-degree relative with colorectai cancer, total energy intake, arid calcium. Czacer C=uses a~d Control. Vol 8. 1997 585

Table 7. Associations between colon cancer and nutrients found in the US multicenter study population No. (cases/controls) = Men Women All subjects Distal Proximal All subjects Distal Proximal OR" (Cl) OR" (Cl) OR= (Cl) OR= (el) OR= (Cl) OR" (Cl) (I ,096/1,290) (542/1,290) (526/1,290) (894/1,120) 142911,120) (446/1 ,I 20) Vegetable proteinb Low 1.0 m 1.0 m 1.0 -- 1.0 m 1.0 -- 1.0 -- 2 1.2 (0.9-1.5 1.1 (0.8-1.5) 1.3 (1.0-1.8) 0.8 (0.6-1.1) 0.9 (0.6-1.3) 0.8 (0.6-1.2) 3 1.0 (0.8-1.3) 0.9 (0.6-1.2) 1.2 (0.6-1.7) 0.9 (0.7-1.2) 0.S (0.5-1.1) 1.0 (0.7-1.4) 4 1.0 (0.8-1.4) 1.1 (0.7-1.5) 1.0 (0.7-1.5) 0.7 (0.5-1.0) 0.7 (0.4-1.0) 0.8 (0.5-1.2) High 0.9 (0.7-1.3) 0.9 (0.6-1.4) 1.0 (0.7-1.6) 0.7 (0.5-1.0) 0.7 (0.5-1.2) 0.7 (0.4-1.2) P trend 0.46 0.56 0.64 0.04 0.08 0.20 Vitamins ~-carotene Low 1.0 ~ 1.0 ~ 1.0 -- 1.0 ~ 1.0 ~ 1.0 -- 2 1.1 (0.8-1.4) 1.0 (0.7-1.4) 1.3 (0.9-1.7) 1.0 (0.7-1.3) 0.8 (0.5-1.1) 1.2 (0.6-1.7) 3 0.9 (0.7-1.1) 0.7 (0.5-1.0) 1.1 (0.7-1.5) 1.2 (0.9-1.6) 1.0 (0.7-1.4) 1.5 (1.0-2.1) 4 1.2 (0.9-1.6) 1.2 (0.8-1.6) 1.3 (0.9-1.8) 1.1 (0.8-1.5) 0.9 (0.6-1.3) 1.4 (0.9-2.1) High 1.1 (0.6-1.5) 1.2 (0.8-1.7) 1.2 (0.8-1.7) 1.3 (0.9-1.8) 1.1 (0.7-1.7) 1.7 (1.1-2.8) P trend 0.40 0.36 0.44 0.16 0.64 0.03 Vitamin C Low 1.0 -- 1.0 -- 1.0 -- 1.0 -- 1.0 ~ 1.0 -- 2 0.9 (0.7-1.2) 0.8 (0.6-1.1) 1.0 (0.7-1.4) 1.1 (0.8-1.5) 1.3 (0.9-1.9) 1.0 (0.7-1.4) 3 1.1 (0.8-1.4) 1.0 (0.7-1.4) 1.1 (0.8-1.6) 1.1 (0.8-1.4) ~.2 (0.8-1.8) 1.0 (0.7-1.4) 4 1.0 (0.6-1.3) 0.9 (0.6-1.3) 1.0 (0.8-1.6) 1.2 (0.9-1.6) 1.2 (0.8-1.7) 1.3 (0.9-1.8) High 0.9 (0.6-1.2) 0.9 (0.6-1.3) 0.8 (0.6-1.3) 1.0 (0.7-1,4) 0.9 (0.6-1.5) 1.1 (0.7-1,8) P trend 0.64 0.76 0.78 0.90 0.68 0.30 Folic acid Low 1.0 m 1.0 -- 1.0 -- 1.0 -- 1.0 m 1.0 -- 2 1.3 (1.0-1.7) 1.4 (1.0-1.9) 1.3 (0.9-1.8) 0.9 (0.7-1.2) 0.7 (0.5-1.0) 1.2 (0.8-1.7) 3 1.1 (0.6-1,4) 1.0 (0.7-1.5) 1.0 (0.7-1,5) 1.0 (0.7-1.4) 0.8 (0.6-1.2) 1.3 (0.9-1.9) 4 0.9 (0.7-1.2) 0.8 (0.7-1.3) 1.0 (0.7-1.4) 0.9 (0.6-1.1) 0.7 (0.5-1.0) 1.0 (0.7-1.6) High 1.2 (0.8-1.6) 1.2 (0.8-1.7) 1.2 (0.8-1.9) 0.9 (0.6-1.3) 0.7 (0.4-1.0) 1.2 (0.8-1.9) P trend 0.70 0.58 0.88 0.38 0.10 0.56 Vitamin Bs Low 1.0 ~ 1.0 -- 1.0 ~ 1.0 ~ 1.0 ~ 1.0 -- 2 0.9 (0.7-1.2) 1.0 (0.7-1.4) 0.8 (0.6-1,1) 0.7 (0.5-0.9) 0.6 (0.4-0.8) 0.7 (0.5-1.0) 3 0.9 (0.7-1.1) 0.9 (0.7-1.2) 0.8 (0.6-1.1) 0.7 (0.5-0.9) 0.6 (0.5-0.9) 0.7 (0.5-1.0) 4 0.8 (0.6-1.0) 0.9 (0.7-1.3) 0.7 (0.5-0.9) 0.7 (0.6-1.0) 0.6 (0.4-0.9) 0.8 (0.6-1.2) High 0.7 (0.6-1.0) 0.7 (0.5-0.9) 0.8 (0.6-1.1) 0.6 (0.5-0.8) 0.6 (0.4-0.8) 0.6 (0.4-0.9) P trend < 0.01 0.02 0.10 < 0.01 < 0.01 0.08 Thiamin Low 1.0 -- 1.0 -- 1.0 -- 1.0 -- 1.0 -- 1.0 ~ 2 0.8 (0.6-1.0) 0.8 (0.6-1.1) 0.7 (0.5-1.0) 0.9 (0.7-1.2) 0.8 (0.6-1.1) 1.0 (0.7-1.4) 3 0.8 (0.6-1.1) 0.8 (0.6-1.1) 0.9 (0.6-1.2) 0.8 (0.6-1.1) 0.6 (0.4-0.8) 1.1 (0.8-1.5) 4 0.7 (0.6-0.9) 0.7 (0.5-1.0) 0.7 (0.6-1.0) 0.9 (0.7-1.2) 0.8 (0.6-1.2) 1.0 (0.7-1.5) High 0.7 (0.5-0.9) 0.6 (0.4-0.9) 0.8 (0.6-1.2) 0.7 (0.5-0.9) 0.6 (0.4-0.9) 0.7 (0.5-1.0) P trend < 0.01 < 0.01 0.26 0.02 0.03 0.18 Niacin Low 1.0 ~ 1.0 ~ 1.0 ~ 1.0 ~ 1.0 ~ 1.0 ~ 2 1.1 (0.6-1.4) 1.0 (0.8-1.4) 1.0 (0.8-1.4) 0.8 (0.6-1.0) 0.9 (0.6-1.3) 0.6 (0.4-0.9) 3 0.9 (0.7-1.2) 0.9 (0.7-1.3) 0.8 (0.6-1.2) 0.9 (0.7-1.2) 1.0 (0.7-1.4) 0.8 (0.6-1.2) 4 1.0 (0.8-1.4) 1.2 (0.8-1.6) 0.9 (0.6-1.3) 0.9 (0.7-1.2). 0.8 (0.5-1.1) 1.0 (0.7-1.4) High 1.0 (0.7-1.3) 1.0 (0.7-1.4) 0.9 (0.7-1.3) 0.8 (0.6-1.0) 0.8 (0.5-1.1) 0.7 (0.5-1.1) P trend 0.72 0.86 0.46 0.22 0.18 0.54 OR = Odds ratio; CI = confidence interval. Model adjusted for age, body mass index (wt/ht2 for men, wt/ht~'s for women), lifetime vigorous leisure time physical activity, use of aspirin/NSAIDS, presence or absence of a first-degree relative with colorectal cancer, total energy intake, and calcium. The cut points for men are as follows: Vegetable protein (g/1,000 Kcal): 9.99, 11.9, 13.4, 15.3; ~-carotene (mcg): 2,538, 3,884, 5,483, 8,475; Vitamin C (mg): 92.4, 128.2, 169.7, 240.4; Folic acid (mcg/1,000 Kcal): 120, 140, 170, 210; B6 (mg/1,000 Kcal): 0.75, 0.87, 1.01, 1.18; Thiamin (mg/1,000 Kcal): 0.69, 0.77, 0.85, 0.96; Niacin (mg/1,000 Kcal): 8.67, 9.87, 11.0, 12.6. For women: Vegetable protein (g/1,000 Kcal): 10.9, 12.5, 14.1, 15.8; I~carotene (mcg): 25.78, 3884, 5609, 8369; Vitamin C (mg): 90.9, 130.2, 168.8, 230.6, Folic acid (mcg/1,000 Kcal): 130, 160, 190, 230; B6 (mg/t,000 Kcal): 0.82, 0.96, 1.08, 1.28; Thiamin (mg/1,000 Kcal): 0.71, 0.79, 0.87, 0.99; Niacin (rag/1,000 Kcal): 8.9, 9.9, 11.2, 12.8. 586 C.~c.er C~u=e~ ~d Conu'oL Vol 8. 1997

Plant foods and colon cancer Table 8. Associations between colon cancer and plant foods adjusting for nutrients found in plant foods in the US multicenter study population Adlustment Men Women Dietary fiber Vegetable Vitamins Dietary fiber Vegetable Vitamins protein protein OR" (Cl) OR" (CI) OR" (Ci) ORa (el) OR= (Cl) OR= (CI) No. (cases/controls) - (1,09911,290) (1,099/1,290) (1,099/1,290) (894/1,120) (894/1,120) (894/1,120) Fruits Low 1.0 i 1.0 i 1.0 -- 1.0 -- 1.0 -- 1.0 -- 2 1.1 (0.9-t.5) 1.1 (0.8-1.4) 1.1 (0.8-1.4) 1.2 (0.9-1.6) 1.2 (0.9-1.5) 1.2 (0.9.1.5) 3 1.2 (0.9-1.6) 1.2 (0.9-1.6) 1.2 (0.9-1.5) 1.0 (0.8-1.4) 1.0 (0.7-1.3) 1.0 (0.7-1.3) 4 1.2 (0.9.1.6) 1.1 (0.9-1.5) 1.1 (0.9.1.5) 1.1 (0.8-1.5) 1.0 (0.8-1.4) 1.0 (0.7-1.4) High 1.3 (1.0-1.8) 1.1 (0.9-1.5) 1.2 (0.8-1.6). 1.2 (0.9-1.7) 1.1 (0.8-1.5) 1.0 (0.7-1.5) Vegetables Low 1.0 ~ 1.0 ~ 1.0 w 1.0 w 1.0 ~ 1.0 -- 2 1.1 (0.9-1.5) 1.1 (0.9-1.4) 1.1 (0.9-1.4) 0.9 (0.7-1.2) 0.9 (0.7-1.2) 0.9 (0.6-1.1) 3 1.0 (0.8-1.3) 1.0 (0.8-1.3) 1.0 (0.8-1.3) 0.9 (0.7-1,2) 0.9 (0.7-1.2) 0.9 (0.7-1.2) 4 1.0 (0.8-1.3) 1.0 (0.7-1.3) 0.9 (0.7-1.2) 0.8 (0.6-1.0) 0.8 (0.6-1.0) 0".7 (0.5-1.0) High 0.8 (0.5-1.1) 0.7 (0.5-1.0) 0.6 (0.5-0.9) 0.8 (0.5-1.1) 0.8 (0.6-1.1) 0.6 (0.4-0.9) Whole grains Low 1.0 w 1.0 w 1.0 ~ 1.0 ~ 1.0 ~ 1.0 ~ 2 0.9 (0.7-1.1) 0.9 (0.7-1.1) 0.8 (0.7-1.1) 1.5 (1.1-2.0) 1,5 (1.1-2.0) 1.5 (1.1-2.0) 3 1.1 (0.9-1.4) 1.1 (0.8-1.4) 1.0 (0.8-1.4) 1.5 (1.1-1.9) 1.5 (1.1-2.0) 1.5 (1.1-2.0) 4 1.0 (0.7-1.3) 1.0 (0.7-1.3) 0.9 (0.7-1.2) 1.5 (1.1-2.1) 1.6 (1.2-2.1) 1.5 (1.1-2.1) High 0.9 (0.6-1.2) 0.8 (0.6-1.1) 0.8 (0.6-1.0) 1.2 (0.9.1.7) 1.3 (0.9-1.7) 1.2 (0.6-1.6) Refined grains Low 1.0 ~ 1.0 ~ 1.0 ~ 1.0 ~ 1.0 ~ 1.0 -- 2 1.4 (1.1-1.8) 1.4 (1.1-1.9) 1.4 (1.1-1.9) 1.2 (0.9-1.6) 1.2 (0.9-t .6) 1.2 (0,9-1.6) 3 1.4 (1.1-1.9) 1.5 (1.1-2.0) 1.5 (1.2-1.9) 1.0 (0.7-1.3) 1.0 (0.6-1.4) 1.0 (0.7-1.3) 4 1.2 (0.9-1.6) 1.3 (1.0-1.7) 1.2 (0.9-1.6) 1,1 (0.9-1.6) 1.2 (0.9-1.6) 1,2 (0.9-1.6) High 1.5 (1.1-2.0) 1.6 (1.2-2.3) 1.5 (1.1-2.1) 1.1 (0.8-1.5) 1.2 (0.8-1.7) 1.1 (0.8-1.6) Nuts and seeds: Low 1.0 ~ 1.0 ~ 1.0 ~ 1.0 -- 1.0 ~ 1.0 -- 2 0.9 (0.8-1.1) 0.9 (0.8-1.1) 0.9 (0.7-1.1) 1.2 (1.0-1.5) 1.2 (1.0-1.5) 1.2 (1.0-1.4) 3 1.1 (0.8-1.5) 1.1 (0.8-1.5) 1.1 (0.8-1.4) 0.9 (0.7-1.3) 0.9 (0.7-1.3) 0.9 (0.7-1.3) High 1.0 (0.7-1.4) 1.0 (0.7-1.4) 0.9 (0.6-1.2) 1.2 (0.8-1.7) 1.3 (0.9-1.8) 1.1 (0.8-1.6) a OR = odds ratio; CI = 95% confidence intervals. All models are adjusted for age, body mass index (wt/ht2 for men, wt/ht~'s for women), lifetime vigorous leisure time physical activity, total energy intake, dietary calcium, use of aspirin/NSAIDS, and presence or absence of a family history of a first-degree relative with coloractal cancer. Model 3 also adjusts for all vitamins shown in Table 7. Cut-points used for men and women are the same as those shown in Table 2. - a finding noted previously in both human and animal s~udies.~':' Canned fruit contributed approximately six percent of sucrose and glucose to the diet of study participants. Although we did not observe a protective effect for fruit juice, it is possible that this category of fruits is more subject to inaccurate recall. It is possible that reported fruit juice is not 100 percent fruit juice, and that people reported fruit drinks, which contain a high sugar content, despite the fact that we asked about juice rather than drinks. Another interpretation of this obser- vation is that individuals eating canned fruit may be consuming lower levels of labile phytochemicals than individuals consuming fresh fruits and vegetables. Plant foods are major contributors of fiber in the diet. Fiber has been associated with reduced risk of colon cancer in other studies)~ We also observed decreased risk for both soluble and insoluble fiber, with the strongest associations being observed for older people and those with proximal tumors. Several mechanisms exist whereby fiber could decrease colon cancer risk, including: decreas- ing transit time; increasing fecal bulk; increasing adsorption of bile acids, fatty acids, and minerals; and providing a fermentable substrate for colonic bacteria. The products of fermentable volatile fatty acids include butyrate which, in addition to being a major colonic epithelial cell. fuel, may play a role in apoptosis and cell C~taccr C,~us~s and Control. Vol 8. 1997 587

IIII Table 9. Interaction between family history of first degree relative with colorectal cancer and intake of plant foods in the US multicenter study population All subjects < 67 years 67+ years 01stal Proximal OR= (CI) ORa (el) OR" (el) OR= (CI) OR" (el) Men Family history/vegetable intake Absent High 1.0 u 1.0 u 1.0 ~ 1.0 -- 1.0 -- Absent Low 1.2 (0.9-1.6) 1.2 (0.8-1.8) 1.3 (0.9-1.9) 1.1 (0.8-1.5) 1.4 (1.0-2.1) Present High 1.9 (1.1-3.4) 2.3 (1.0-5.4) 1.7 (0.8-3.8) 1.9 (1.0-3.6) 2.0 (1.0-4.2) Present Low 3.1 (1.8-5.2) 3.7 (1.5-8.9) 2.9 (1.5-5.8) 2.5 (1.3-4.6) 3.9 (2.1-7.2) Family history/refined grains Absent Low 1.0 -- 1.0 -- 1,0 ~ 1.0 -- 1.0 -- Absent High 1.4 (1.0-1,8) 1,5 (1.0-2.3) 1,2 (0.8-1.9) 1.4 (1.0-2.1) 1.3 (0.9-1.9) Present Low 1.8 (1.0-3.2) 1.5 (0.6-4.0) 1,9 (1.0-3.8) 1.2 (0.5-2.5) 2.2 (1.2-4.3) Present High 4.0 (2.3-7.2) 7.2 (2.9-17.8) 2,4 (1.1-5.3) 4.4 (2.3-8.5) 3.4 (1.7-6.9) Women Family history/vegetable intake Absent High 1.0 -- 1.0 ~ 1.0 ~ 1.0 ~ 1,0 u Absent Low 1.5 (1.1-2.0) 1.9 (1.2-2.8) 1.3 (0.8-2.0) 1.3 (0.9-1.9) 1.7 (1,2-2.5) Present High 1.7 (1.0-3.1) 2,3 (1.0-5.2) 1.3 (0.6-2.9) 1.3 (0.6-2.7) 2.3 (1,2-4.5) Present Low 2.0 (1.1-3.6) 1.9 (0.7-4.9) 2.1 (1.0-4.3) 1.9 (0.9-3,8) 2.7 (1.2-4.7) Family history/refined grains Absent Low 1.0 -- 1.0 -- 1.0 ~ 1.0 ~ 1.0 ~ Absent High 1.0 (0.8-1.4) 0.9 (0.6-1.5) 1.2 (0.8-1.9) 1.0 (0.7-1.5) 1.1 (0.7-1.6) Present Low 1.8 (1.0-3.2) 1.9 (0.6-5.8) 1.8 (0.9-3.5) 1.9 (0.9-3.7) 1.8 (0.9-3,5) Present High 1.5 (0.9-2.8) 2.2 (0,9-5.3) 1.0 (0.4-2.4) 1.0 (0.4-2.1) 2.1 (1.1-4.3) OR = Odds ratio; CI = confidence interval. Model adjusted for age, body mass index (wt/ht~ for men, wt/htl"s for women), lifetime vigorous leisure time physical activity, use of aspirin/NSAID, total energy intake, and calcium. replication.2~ Fruits and vegetables also are major sources of pectin which is generally water soluble; outside of the colon, pectin reduces the rate of glucose absorption and decreases the rate of absorption and/or availability of lipids?° Stronger associations of fiber with proximal tumors may reflect the role of fiber in bile acid absorption, which may play a larger role in proximal cfdistal tumors21 While it has been hypothesized that starch may decrease risk of colon cancer because of its fermentable proper- des,S= in this study we did not observe an association with colon cancer. It also has been argued that the relationship of fiber to colon cancer could be explained by phytic acid commonly found in nuts and seed and grains." We did not find a protective effect for nuts and seeds or refined grains; phytic acid commonly found in these foods could alter risk in either way as it binds dietary calcium, a factor which has been suggested to be protective for colon cancer.~ The associations of vit='w~ins commo.[y found in plant foods with colon cancer have been less clear in the litera- ture. Vitamins with antioxidant properties, including ~-carotene and vitamin C, have been examined in several studies and have been shown to decrease colon cancer risk in some, although not all studies.~a' p-carotene increased recurrence of large polyps in an intervention trial.~ In this study, we observed an increase in risk asso- ciated with vitamin A activity {rom plant foods (designed 588 Cancer Causes and Control. Vol 8. 1997 as ~-carotene in the NCC database) among women with proximal tumors: vitamin C was not found to alter risk of colon cancer. However, given the association we observed with specific foods, such as tomatoes, there are suggestions that other carotenoids, such as lycopene, may be associated more strongly with a lower risk of colon cancer than ~-carotene. Of the vitamins examined, vitamins Bs and thiamin showed the most protection for colon cancer. Vitamin Bs, also commonly found in fruits and vegetables, is involved in the metabolism of sulfur-containing amino adds. Pyri- doxal phosphate, the coenzyme form of vitamin Bs, is required for transulfhydration reactions in which cysteine is synthesized from methionlne, the major methyl donor in the body.~ Deficiencies of Bs can result in increased excretion of metabolites of methionine. Both folate and Bs may reduce colon cancer risk by reducing the likeli- hood of DNA hypomethylation, an early step in the colon cancer process.~* Folate was protective only among women with distal tumors, which is similar to reports by others.~°,~ Niacin is converted into active forms of niacinamide nucleotides, NAD and NADP(H), in mucosal cells. These nucleotides are involved in oxidative reactions, fatty acid synthesis, cholesterol and steroid hormone synthesis, synthesis of glutamate, synthesis of deoxyribonucleotides,

and" protein synthesis. NAD is a substrate in adenosine diphosphoribose (ADP-ribose) transfer reactions; a rapid biochemical response to carcinogen-induced DNA damage is synthesis of ADP-ribose polymers from NAD.4' These observations suggest that niacin is involved in the regulation of many cellular processes.~2 Niacin is also a component of the glucose tolerance factor that potentiates the action of insulin; it has been hypothesized that insulin is associated with cancer.~ At the cellular level, thiamin is involved in energy transformation and the synthesis of nicotinamide adenine dinucleotide phosphate (NADPH), a co-enzyme form of niacin. Absorption of thiamin is impaired by low levels of folate and high levels of alcohol.37 For many foods and nutrients, associations were slightly stronger for proximal tumors. These observations may be explained in part by bioactive dietary constituents such as phytoestrogensTM found in plant foods. The role of such compounds when present in large amounts may be markedly different before and after menopause in women, while only gradually changing their impact with age in men; this may account for the slightly stronger associations observed for plant foods for women than for men. Phytoestrogens may influence the methylation of the estrogen receptor gene,'S which is silenced in colon tumors.~ Endogenous estrogens have been hypothesized to be associated more with proximal tumors than with distal tumors; ~1 it is possible that phytoestrogens have similar associations. There are study limitations. Since the purpose of this study was to examine plant foods and colon cancer, we limited our analyses to nutrients from foods, the associa- tions reported here do not take supplements into account. Thus, studies which have included nutrients from supplements may observe different associations. Also, exposure information in this study is based on one uniform time period (two years prior to diagnosis); if other periods of exposure are more relevant to disease, then associations reported here may not capture the most important time period of action. Another limitation is our inability to examine many bioacdve compounds found in plant foods. Although we have attempted to do this by examining food groups, a complete analysis is impossible using existing nutrient databases. As we obtain more information on phytochemicals, we will be able to examine bioacdve components of plant foods in relation to colon cancer. It also is possible that case subjects may have reported their diet differently because of their disease, however fruit- and vegetable-specific associations argue against any selective recall. While it could be argued that the findings reported here are the result of making many comparisons, the primary objective of the study was to evaluate colon cancer asso- ciations for gender-, age-, and site-specific groups. We Plant foods and colon cancer believe that the purpose of epidemiologic studies is to conduct a scientific inquiry into etiology and possible biological mechanisms by summarizing and interpreting the data in a relevant and informative manner given back- ground theory and knowledge. It is undesirable to sacrifice power for the sake of maintaining the study's type I error probability. Further, it has been argued that a universal null hypothesis is rarely applicable in obser- vational studies such as the one conducted here.° In summary, results suggest that plant foods and many dietary constituents contained in plant foods are associ- ated with colon cancer. Some of these constituents of plants, such as dietary fiber, have been reported previously as decreasing risk of colon cancer. Other factors, such as several B vitamins, have not been reported previously as decreasing risk of colon cancer;, in this population they appear to be associated inversely with colon cancer. These associations provide additional insight into possible mechanisms whereby plant foods may alter colon cancer risk. Our data suggests that mechanisms exist whereby plant foods decrease risk of colon cancer unrelated to standard micronutrients, since adjustment for known measurable constituents of plant foods did not apprecia- bly alter the observed associations between plant foods and risk of colon cancer. Thus, it seems prudent to consume a diet high in vegetables, certain fruits, and whole grains as a way to reduce risk of colon cancer. Acknowledgement n We acknowledge the contribu- tions to data collection by Sandra Edwards, Dr Richard Kerber, and Dr Kristin Anderson. References I. Slavin.~. Epidemiological evidence for the impact of whole grains on health. CHt Re~ Food Sci Muir 1994; 34: 427-34. 2. Steinmetz KA, PotterJD. Vegetables, fruits, and cancer. If. Mechanisms. Cancer Causes Control 1991; 2: 427-42. 3. Potter JD, Slattery ML, Bostick RM, Gapstur SM. Colon cancer:. A review of the epidemiology. Epidemiol Rev 1993; 15: 499-545. 4. Howe G, Benito E, Duff'y S, et al. Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case=control studles.JNCI 1992; 84: 1887-96. 5. West DW, Slattery ML, Robison LM, et al. Dietary intake and colon Cancer'. Sex and anatomical site-specific associa- tions. AmJ Epideraiol 1989; 130: 883-94. 6. Whittemore AS, Wu=Williams AH, Lee M, et al. 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