Dietary Fiber and the Risk of Colorectal Cancer and Adenoma in Women
Charles S. Fuchs, M.D., Edward L. Giovannucci, M.D., Graham A. Colditz, M.D., David J. Hunter, M.B., B.S., Meir J. Stampfer, M.D., Bernard Rosner, Ph.D., Frank E. Speizer, M.D., and Walter C. Willett, M.D.
Background A high intake of dietary fiber has been thought toreduce the risk of colorectal cancer and adenoma.
Methods We conducted a prospective study of 88,757 women, whowere 34 to 59 years old and had no history of cancer, inflammatorybowel disease, or familial polyposis, who completed a dietaryquestionnaire in 1980. During a 16-year follow-up period, 787cases of colorectal cancer were documented. In addition, 1012patients with adenomas of the distal colon and rectum were foundamong 27,530 participants who underwent endoscopy during thefollow-up period.
Results After adjustment for age, established risk factors,and total energy intake, we found no association between theintake of dietary fiber and the risk of colorectal cancer; therelative risk for the highest as compared with the lowest quintilegroup with respect to fiber intake was 0.95 (95 percent confidenceinterval, 0.73 to 1.25). No protective effect of dietary fiberwas observed when we omitted adjustment for total energy intake,when events during the first six years of follow-up were excluded,or when we excluded women who altered their fiber intake duringthe follow-up period. No significant association between fiberintake and the risk of colorectal adenoma was found.
Conclusions Our data do not support the existence of an importantprotective effect of dietary fiber against colorectal canceror adenoma.
The rarity of colorectal cancer in Africa suggested to Burkittseveral decades ago that the high-fiber diet of Africans wasprotective against colorectal cancer.1 Since then, dietary fiberhas been postulated to prevent colorectal cancer by dilutingor adsorbing fecal carcinogens, reducing colonic transit time,altering bile acid metabolism, reducing colonic pH, or increasingthe production of short-chain fatty acids.2
Despite the intuitive appeal of Burkitt's hypothesis, epidemiologicstudies of a possible link between dietary fiber and colorectalcancer have been inconclusive.3 The limited data on other dietaryfactors included in most studies did not permit a clear distinctionto be made between the effects of fiber and those of other constituentsof plant foods. Moreover, the retrospective design of thesestudies may have introduced recall and selection biases.
We prospectively examined the relation between fiber intakeand the risk of colorectal cancer in a large cohort of women.In an earlier report based on 150 cases of colorectal cancerreported during six years of follow-up,4 we observed a minimalinverse association that was not statistically significant.In the present analysis, we extend follow-up to 16 years inorder to examine more thoroughly the influence of dietary fiberon the risk of colorectal cancer and adenoma.
Methods
Study Cohort
The Nurses' Health Study was initiated in 1976, when 121,700female registered nurses who were 30 to 55 years of age andresiding in the United States completed a mailed questionnaireon known or suspected risk factors for cancer and coronary heartdisease.5 Since then, the women have been sent follow-up questionnairesevery two years to bring information on these risk factors upto date and to identify newly diagnosed cases of cancer andother diseases. Dietary intake was first assessed in 1980, whenthe women completed a mailed semiquantitative food-frequencyquestionnaire. For this analysis, we excluded women who left10 or more items blank on the 1980 food-frequency questionnaire,those with implausibly high or low scores for total energy intake,and those who reported a history of cancer (except nonmelanomaskin cancer), ulcerative colitis, Crohn's disease, or a familialpolyposis syndrome. After these exclusions, 88,757 women remainedeligible for follow-up from 1980 through 1996.
Data on Dietary Fiber and Other Factors
The study women provided information on their smoking history,age, height, weight, level of physical activity, aspirin use,family history of colorectal cancer, and any examination bycolonoscopy or sigmoidoscopy, as well as the indications forthe procedure.
In 1980 the semiquantitative food-frequency questionnaire included61 items; the 1984 questionnaire was expanded to 121 items,and the 1986 questionnaire included 136 items. For each foodlisted, a commonly used unit or portion size was specified andparticipants were asked how often, on average, they had consumedthat amount of each food over the past year; there were ninepossible responses. We also asked about the brand of breakfastcereal and multivitamin typically used and provided an open-endedsection for foods not listed. We computed nutrient intakes bymultiplying the frequency of consumption of each food by thenutrient content of the specified portions, using compositionvalues from Department of Agriculture sources supplemented withother data, including the components of specific multivitaminsand breakfast cereals.6 Values for total dietary fiber werebased on the work of Southgate and colleagues.7 All nutrientsand dietary fiber were adjusted for total energy intake by theresiduals method.8 At base line, we did not collect informationon fiber supplements; on the 1994 questionnaire, fewer than6 percent of the women were taking plantago-seed (psyllium-seed)supplements regularly.
The reproducibility and validity of these questionnaires havebeen documented previously.9,10 The energy-adjusted correlationfor crude intake of fiber as measured by the 1980 questionnaireand as calculated from records of dietary intake of weighedfoods in 1980 was 0.61.10 Similarly, the correlation betweencrude intake of fiber as reported in the 1984 questionnaireand that found in the 1980 dietary records of weighed portionswas 0.56.11 Among the chief contributors to dietary fiber, theenergy-adjusted correlations between intake as reported on the1980 questionnaire and in the dietary records were 0.71 forwhite bread, 0.77 for dark bread, 0.79 for cold cereal, 0.80for apples, 0.74 for oranges, 0.79 for bananas, 0.50 for peas,0.73 for tomatoes, 0.63 for string beans, and 0.69 for broccoli.12
Identification of Cases of Colorectal Cancer or Adenoma
On each questionnaire we inquired whether colon or rectal cancerhad been diagnosed and, if so, requested the date of the diagnosis.For this analysis, the follow-up data were available for 96percent of the total possible person-years. Most of the deathsin the cohort were reported by family members or the postalsystem in response to the follow-up questionnaires. In addition,we used the National Death Index, a highly sensitive methodof identifying deaths among nonrespondents.13 When a woman (orthe next of kin) reported a diagnosis of colorectal cancer,we asked for permission to obtain medical records and pathologyreports. A study physician blinded to the womens' exposure andintake data reviewed all records and extracted data on the histologictype, anatomical location, and stage of cancer. We excludedthe small number of cancers that were not adenocarcinomas, aswell as carcinomas in situ. This left 787 cases of invasivecolorectal adenocarcinoma.
The analysis of adenomas was restricted to women who were eligiblefor the analysis of cancer and who reported undergoing colonoscopyor sigmoidoscopy during the study period. Because the reviewof medical records for cases of adenoma has been completed onlythrough 1994, the study period for adenomas was defined as 1980through 1994. After these exclusions, 27,530 women were eligiblefor this portion of the analysis. When a woman reported a diagnosisof a colorectal polyp, we obtained medical records and pathologyreports. A study physician unaware of the risk-factor data reviewedall records and extracted data on the type, location, and sizeof the adenoma.14 Because a sigmoidoscopic examination encompassesonly the distal portion of the colon and rectum and becausea substantial portion of those who underwent endoscopy had asigmoidoscopy, we assessed only adenomas of the descending colonand rectum. Women with adenomas proximal to the descending colonwere not classified as having adenoma in this analysis. Thisleft 1012 patients with adenomas of the distal colon and rectum.
Statistical Analysis
Women were categorized according to quintiles with respect tototal fiber intake and intake of specific types of fiber ascomputed from the 1980, 1984, and 1986 dietary questionnaires.For the primary analysis, we used incidence rates, with person-yearsof follow-up as the denominator. For each woman, person-yearsof follow-up were counted from the date of the return of thebase-line questionnaire until the date of a diagnosis of colorectalcancer or death or until May 31, 1996. We used relative riskas a measure of association, defined as the incidence of colorectalcancer among study women in each quintile of fiber intake dividedby the corresponding rate among the women in the lowest quintile.Age-adjusted relative risks were calculated after stratification,according to five-year age categories. Proportional-hazardsmodels were used to adjust for multiple risk factors simultaneously.Stratified analyses were conducted to determine whether theinfluence of fiber intake was modified by other risk factorsfor colorectal cancer. All P values are two-sided.
To evaluate the influence of measurement error on our findings,we used a correction procedure that adjusts the relative risksand confidence intervals to account for errors in assessingfiber intake.15 This procedure requires a "gold standard" fora subgroup of the women in order to calibrate the questionnaireused in the entire cohort; for this, we used detailed dietaryrecords of weighed portions of food collected for 28 days overa 1-year period for a subgroup made up of 173 participants.10
Results
During the 16 years of follow-up (1,408,232 person-years), wedocumented 787 cases of colorectal cancer among the 88,757 eligiblewomen. Within the entire cohort, the median energy-adjustedtotal dietary fiber intake differed by more than a factor of2.5 between the highest and the lowest quintiles (Table 1).Women who consumed more fiber were older, less likely to havesmoked cigarettes, and more apt to exercise regularly, to havea family history of colorectal cancer, and to undergo screeningendoscopy. In addition, women who reported higher fiber intakeconsumed less red meat and alcohol but more folate, calcium,and vitamin D.
Table 1. Base-Line Characteristics of the Study Cohort.
In age-adjusted and multivariate analyses based on data fromthe 1980 questionnaire and 16 years of follow-up, energy-adjustedtotal dietary fiber intake was not significantly associatedwith the incidence of colorectal cancer (Table 2). Moreover,there was no relation between total dietary fiber intake andthe risk of cancer in the proximal or distal colon. There wasalso no relation when dietary fiber was analyzed without adjustmentfor total energy intake (multivariate relative risk of colorectalcancer in the highest as compared with the lowest quintile,1.17; 95 percent confidence interval, 0.91 to 1.51) or whenwe analyzed crude fiber (multivariate relative risk, 0.96; 95percent confidence interval, 0.73 to 1.25).
Table 2. Relative Risk of Colorectal Cancer According to Total Dietary Fiber Intake in 1980.
Because the variation in fiber intake within the highest quintilewas much greater than that within the other quintiles (Table 1),we also analyzed total fiber as a continuous variable. Inmultivariate analyses, each increment of 10 g per day in totalfiber intake corresponded to a relative risk of colorectal cancerof 0.99 (95 percent confidence interval, 0.83 to 1.17). To evaluateextreme levels of dietary fiber consumption, we repeated ouranalysis after categorizing fiber intake according to energy-adjusteddeciles. As compared with women in the lowest decile (medianintake, 8.5 g per day), women in the highest decile (medianintake, 28.5 g per day) had a relative risk of colorectal cancerof 1.01 (95 percent confidence interval, 0.71 to 1.43).
Since previous work has suggested that fiber from various foodsources may be related to colorectal cancer in different ways,we computed the contributions of dietary fiber from cereals,fruits, and vegetables (Table 3). Only fruit fiber was associatedwith any appreciable reduction in risk (multivariate relativerisk, 0.86; 95 percent confidence interval, 0.67 to 1.10), butthe overall trend was not statistically significant (P=0.16).In contrast, greater consumption of vegetable fiber was associatedwith a significant increase in the risk of colorectal cancer(multivariate relative risk, 1.35; 95 percent confidence interval,1.05 to 1.72; P for trend=0.004).
Table 3. Relative Risk of Colorectal Cancer According to Dietary Intake of Fiber from Various Sources in 1980.
To examine the possibility that total dietary fiber influencesthe risk of colorectal cancer only after several years, we analyzedthe relation between dietary fiber as assessed in 1980 and therisk of colorectal cancer from 1986 through 1996. Despite thesix-year latency period, greater dietary fiber intake was notassociated with a reduction in the risk of colorectal cancer(multivariate relative risk, 1.00; 95 percent confidence interval,0.72 to 1.38).
Among the women who returned the 1980 questionnaire, 65,186women also completed a longer and more detailed dietary questionnairein 1986. In an analysis based on the 1986 questionnaire andthe incidence of cancer from 1986 through 1996, no significanttrend was observed between energy-adjusted dietary fiber intakeand the risk of colorectal cancer (multivariate relative risk,0.98; 95 percent confidence interval, 0.72 to 1.34). We alsoexamined the risk of colorectal cancer according to the meandietary fiber intake in 1980, 1984, and 1986 and found no association(multivariate relative risk for the highest as compared withthe lowest quintile, 1.00; 95 percent confidence interval, 0.69to 1.47).
We assessed the effect of consistent fiber intake over a six-yearinduction period. After classifying the women according to theirfiber intake in 1980, we excluded those who subsequently increasedor decreased their fiber intake by more than one quintile asreported on either the 1984 or the 1986 questionnaire. Amongwomen who maintained a consistent level of fiber intake from1980 through 1986, dietary fiber intake was not associated witha reduction in the risk of colorectal cancer from 1986 through1996 (Table 4). Similarly, neither consistent consumption offiber from cereal nor consistent intake of vegetable fiber wasassociated with a reduction in the incidence of colorectal cancer.
Table 4. Relative Risk of Colorectal Cancer among Women with Consistent Fiber Intake.
We found no evidence of an inverse association between fiberand colorectal cancer in any subgroup defined by age, familyhistory of colorectal cancer, aspirin use, physical activity,body-mass index, cigarette smoking, or total intake of fat (Table 5),or by intake of alcohol, red meat, methionine, calcium,or vitamin D (data not shown). We did find an inverse relationbetween total dietary fiber intake and the incidence of colorectalcancer among women in the lowest third of the group with respectto folate consumption. Within this stratum, the inverse associationwas restricted to fruit fiber (relative risk for the highestas compared with the lowest quintile of fruit fiber, 0.59; 95percent confidence interval, 0.35 to 0.99; P for trend=0.06).
Table 5. Relative Risk of Colorectal Cancer According to Dietary Fiber Intake in Subgroups Defined by Selected Variables.
To evaluate possible distortion of our findings by higher ratesof screening endoscopy among women who consumed more dietaryfiber, we repeated our analysis after stratification accordingto whether or not women had undergone screening endoscopy duringthe study period; we found no inverse relation between fiberintake and colorectal cancer in either stratum (Table 5). Wealso repeated our analysis after excluding women whose cancersmay have been detected incidentally or only by screening (Dukes'stages A and B). When we restricted the outcome to more advancedlesions in this way, the relative risk for the highest as comparedwith the lowest quintile with respect to fiber intake was 0.94(95 percent confidence interval, 0.62 to 1.44).
Errors in assessing dietary fiber intake could have biased therelative risks. When we adjusted for age and total energy intake,the relative risk of colorectal cancer associated with a 10-gincrease in daily total dietary fiber intake was 1.00 (95 percentconfidence interval, 0.89 to 1.13). After adjustment for errorsin measuring fiber and total energy intake, the relative riskassociated with a 10-g increase was still 1.00 (95 percent confidenceinterval, 0.74 to 1.36).
We also assessed the relation between fiber intake and the riskof distal colorectal adenomas among 27,530 women who reportedundergoing colonoscopy or sigmoidoscopy between 1980 and 1994.There was no reduction in the risk of colorectal adenoma withincreasing dietary intake of total, cereal, fruit, or vegetablefiber, even when we restricted our analysis to women who hadundergone endoscopy before 1980 and had been determined at thattime to be free of polyps (Table 6).
Table 6. Relative Risk of Distal Colorectal Adenoma According to Dietary Fiber Intake in 1980.
Discussion
In this large, prospective cohort study, we found no evidencethat dietary fiber reduces the risk of colorectal cancer. Thisresult is unlikely to be due to imprecise measurement of fiberintake or to biased ascertainment of colorectal cancers. Ourprospective study design precluded bias attributable to differentialrecall of intake by women with and without cancer. Variationin fiber intake over time was not a factor, because our resultsremained unchanged when we excluded women who substantiallyaltered their fiber intake during the first six years of observation.
By means of a food-frequency questionnaire, we were able toexamine the influence of fiber at recommended intakes (25 to35 g per day),16 which are considerably higher than the meandietary fiber intake in the U.S. adult population (13.3 g perday).17 The fact that, in this cohort and others, strong inverseassociations between fiber intake and the incidence of symptomaticdiverticular disease,18 coronary heart disease,19 hypertension,20,21and non-insulin-dependent diabetes mellitus22 were observedin studies using the same questionnaire suggests that we useda physiologically relevant measure of fiber intake.
We cannot rule out a weak association between fiber intake andcolorectal cancer, an effect of fiber early in life, or an influenceof the consumption of more than 30 to 35 g of fiber per day.However, the last association would imply a nonlinear relationbetween fiber intake and the risk of colorectal cancer, whichis not suggested by the previous retrospective studies.
Evidence for the hypothesis that fiber intake is related tothe risk of colon cancer has been inconclusive. A meta-analysisof case–control studies demonstrated a combined odds ratioof 0.58 for colon cancer in the highest as compared with thelowest quintile of fiber intake.23 However, when this analysiswas restricted to studies that used validated dietary questionnairesand incorporated qualitative data into estimates of nutrientintakes, the relative-risk estimates for colorectal cancer associatedwith consumption of more dietary fiber were closer to 1.00.24In five large, prospective studies,25,26,27,28,29 inverse associationsbetween the intake of fiber and the risk of colon cancer wereweak or nonexistent. Using a limited dietary questionnaire,Thun et al. did find a significant inverse relation betweenthe intake of "citrus fruit, vegetable, and high-fiber grains"and colon cancer, although dietary fiber intake was not specificallyanalyzed.30 Moreover, three placebo-controlled, randomized trialsfound no significant reduction in the incidence of colorectaltumors among subjects who received fiber supplementation.31,32,33A recent prospective study of 16,448 U.S. men also did not finda significant association between the dietary intake of total,cereal, or vegetable fiber and colorectal adenomas, althougha slight reduction in risk was observed with increasing intakeof fruit fiber.34
Many previous studies assessed a limited number of potentialconfounders. One of these, folate, occurs in plant foods andmay protect against colon cancer.3,35,36 In our analysis, adjustmentfor folate intake did attenuate the weak association betweenfiber and colorectal cancer.
The significant positive association between the intake of vegetablefiber and the risk of colorectal cancer was unexpected. In aprospective study of 41,837 middle-aged women, Steinmetz etal. observed an increased risk of colon cancer with greaterconsumption of cruciferous vegetables and potatoes.29 In ourown study, however, we found no link between vegetable-fiberintake and the risk of adenoma.
There are cogent reasons for increasing fiber intake, particularlythe inverse association with coronary heart disease observedin many studies.19,37 However, we found no evidence to supportthe hypothesis that total dietary fiber intake is protectiveagainst colorectal cancer or adenoma.
Supported by grants (HL 34594 and CA 40356) from the NationalInstitutes of Health and by an Academic Award in PreventiveOncology from the National Institutes of Health (CA 66385, toDr. Fuchs).
Source Information
From the Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (C.S.F., E.L.G., G.A.C., D.J.H., M.J.S., B.R., F.E.S., W.C.W.); the Department of Adult Oncology, Dana–Farber Cancer Institute (C.S.F.); and the Departments of Epidemiology (G.A.C., D.J.H., M.J.S., W.C.W.), Environmental Health (F.E.S.), Nutrition (E.L.G., M.J.S., W.C.W.), and Biostatistics (B.R.), Harvard School of Public Health — all in Boston.
Address reprint requests to Dr. Fuchs at the Dana–Farber Cancer Institute, 44 Binney St., Boston, MA 02115.
References
Burkitt DP. Epidemiology of cancer of the colon and rectum. Cancer 1971;28:3-13. [CrossRef][Medline]
Kritchevsky D. Epidemiology of fibre, resistant starch and colorectal cancer. Eur J Cancer Prev 1995;4:345-352. [CrossRef][Medline]
Giovannucci E, Willett WC. Dietary factors and risk of colon cancer. Ann Med 1994;26:443-452. [Medline]
Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Speizer FE. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N Engl J Med 1990;323:1664-1672. [Abstract]
Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Hennekens CH, Speizer FE. Dietary fat and the risk of breast cancer. N Engl J Med 1987;316:22-28. [Abstract]
Department of Agriculture. Composition of foods: raw, processed, prepared. Agricultural handbook no. 8. Washington, D.C.: Government Printing Office, 1963–1988.
Southgate DA, Bailey B, Collinson E, Walker AF. A guide to calculating intakes of dietary fibre. J Hum Nutr 1976;30:303-313. [Medline]
Willett W, Stampfer MJ. Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 1986;124:17-27. [Free Full Text]
Giovannucci E, Colditz G, Stampfer MJ, et al. The assessment of alcohol consumption by a simple self-administered questionnaire. Am J Epidemiol 1991;133:810-817. [Free Full Text]
Willett WC, Sampson L, Stampfer MJ, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 1985;122:51-65. [Free Full Text]
Willett WC, Sampson L, Browne ML, et al. The use of a self-administered questionnaire to assess diet four years in the past. Am J Epidemiol 1988;127:188-199. [Free Full Text]
Salvini S, Hunter DJ, Sampson L, et al. Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. Int J Epidemiol 1989;18:858-867. [Free Full Text]
Stampfer MJ, Willett WC, Speizer FE, et al. Test of the National Death Index. Am J Epidemiol 1984;119:837-839. [Free Full Text]
Giovannucci E, Colditz GA, Stampfer MJ, et al. A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in U.S. women. J Natl Cancer Inst 1994;86:192-199. [Free Full Text]
Rosner B, Spiegelman D, Willett WC. Correction of logistic regression relative risk estimates and confidence intervals for measurement error: the case of multiple covariates measured with error. Am J Epidemiol 1990;132:734-745. [Free Full Text]
Diet, nutrition, and cancer prevention: a guide to food choices. Bethesda, Md.: National Institutes of Health, 1984. (NIH publication no. 87-2711.)
Lanza E, Jones DY, Block G, Kessler L. Dietary fiber intake in the US population. Am J Clin Nutr 1987;46:790-797. [Free Full Text]
Aldoori WH, Giovannucci EL, Rimm EB, Wing AL, Trichopoulos DV, Willett WC. A prospective study of diet and the risk of symptomatic diverticular disease in men. Am J Clin Nutr 1994;60:757-764. [Free Full Text]
Rimm EB, Ascherio A, Giovannucci E, Spiegelman D, Stampfer MJ, Willett WC. Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. JAMA 1996;275:447-451. [Free Full Text]
Ascherio A, Hennekens C, Willett WC, et al. Prospective study of nutritional factors, blood pressure, and hypertension among US women. Hypertension 1996;27:1065-1072. [Free Full Text]
Ascherio A, Rimm EB, Giovannucci EL, et al. A prospective study of nutritional factors and hypertension among US men. Circulation 1992;86:1475-1484. [Free Full Text]
Salmeron J, Manson JE, Stampfer MJ, Colditz GA, Wing AL, Willett WC. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. JAMA 1997;277:472-477. [Free Full Text]
Howe GR, Benito E, Castelleto R, 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 studies. J Natl Cancer Inst 1992;84:1887-1896. [Free Full Text]
Friedenreich CM, Brant RF, Riboli E. Influence of methodologic factors in a pooled analysis of 13 case-control studies of colorectal cancer and dietary fiber. Epidemiology 1994;5:66-79. [Erratum, Epidemiology 1994;5:385.] [Medline]
Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC. Intake of fat, meat, and fiber in relation to risk of colon cancer in men. Cancer Res 1994;54:2390-2397. [Free Full Text]
Goldbohm RA, Van der Brandt PA, Van 't Veer P, Dorant E, Sturmans F, Hermus RJ. Prospective study on alcohol consumption and the risk of cancer of the colon and rectum in the Netherlands. Cancer Causes Control 1994;5:95-104. [CrossRef][Medline]
Heilbrun LK, Nomura A, Hankin JH, Stemmermann GN. Diet and colorectal cancer with special reference to fiber intake. Int J Cancer 1989;44:1-6. [Medline]
Kato I, Akhmedkhanov A, Koenig K, Toniolo PG, Shore RE, Riboli E. Prospective study of diet and female colorectal cancer: the New York University Women's Health Study. Nutr Cancer 1997;28:276-281. [Medline]
Steinmetz KA, Kushi LH, Bostick RM, Folsom AR, Potter JD. Vegetables, fruit, and colon cancer in the Iowa Women's Health Study. Am J Epidemiol 1994;139:1-15. [Free Full Text]
Thun MJ, Calle EE, Namboodiri MM, et al. Risk factors for fatal colon cancer in a large prospective study. J Natl Cancer Inst 1992;84:1491-1500. [Free Full Text]
DeCosse JJ, Miller HH, Lesser ML. Effect of wheat fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis. J Natl Cancer Inst 1989;81:1290-1297. [Free Full Text]
MacLennan R, Macrae F, Bain C, et al. Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas: the Australian Polyp Prevention Project. J Natl Cancer Inst 1995;87:1760-1766. [Free Full Text]
McKeown-Eyssen GE, Bright-See E, Bruce WR, Jazmaji V. A randomized trial of a low fat high fibre diet in the recurrence of colorectal polyps: Toronto Polyp Prevention Group. J Clin Epidemiol 1994;47:525-536. [CrossRef][Medline]
Platz EA, Giovannucci E, Rimm EB, et al. Dietary fiber and distal colorectal adenoma in men. Cancer Epidemiol Biomarkers Prev 1997;6:661-670. [Free Full Text]
Glynn SA, Albanes D. Folate and cancer: a review of the literature. Nutr Cancer 1994;22:101-119. [Medline]
Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998;129:517-524. [Free Full Text]
Willett W. Nutritional epidemiology. New York: Oxford University Press, 1990.
Dietary Fiber and Colorectal Cancer
Ravin N. D., Mohandas K.M., Cummings J. H., Southgate D. A.T., Heaton K. W., Lewis S. J., Madar Z., Stark A., Camire M. E., Fuchs C. S., Willett W. C.
Extract |
Full Text
N Engl J Med 1999;
340:1924-1926, Jun 17, 1999.
Correspondence
This article has been cited by other articles:
Timm, D. A., Slavin, J. L.
(2008). Dietary Fiber and the Relationship to Chronic Diseases. AMERICAN JOURNAL OF LIFESTYLE MEDICINE
2: 233-240
[Abstract]
Toden, S., Bird, A. R., Topping, D. L., Conlon, M. A.
(2007). High red meat diets induce greater numbers of colonic DNA double-strand breaks than white meat in rats: attenuation by high-amylose maize starch. Carcinogenesis
28: 2355-2362
[Abstract][Full Text]
Guerreiro, C. S, Cravo, M. L, Brito, M., Vidal, P. M, Fidalgo, P. O, Leitao, C. N
(2007). The D1822V APC polymorphism interacts with fat, calcium, and fiber intakes in modulating the risk of colorectal cancer in Portuguese persons. Am. J. Clin. Nutr.
85: 1592-1597
[Abstract][Full Text]
Wakai, K., Date, C., Fukui, M., Tamakoshi, K., Watanabe, Y., Hayakawa, N., Kojima, M., Kawado, M., Suzuki, K., Hashimoto, S., Tokudome, S., Ozasa, K., Suzuki, S., Toyoshima, H., Ito, Y., Tamakoshi, A., for the JACC Study Group,
(2007). Dietary Fiber and Risk of Colorectal Cancer in the Japan Collaborative Cohort Study. Cancer Epidemiol. Biomarkers Prev.
16: 668-675
[Abstract][Full Text]
Hudson, T. S., Forman, M. R., Cantwell, M. M., Schatzkin, A., Albert, P. S., Lanza, E.
(2006). Dietary Fiber Intake: Assessing the Degree of Agreement between Food Frequency Questionnaires and 4-Day Food Records.. J. Am. Coll. Nutr.
25: 370-381
[Abstract][Full Text]
Kostikas, K., Papaioannou, A. I., Gourgoulianis, K. I., Etzel, C. J., Kachroo, S., Yanai, H., Yoshida, H., Tada, N., Jacobson, B. C., Camargo, C. A. Jr.
(2006). BMI and Gastroesophageal Reflux in Women. NEJM
355: 848-850
[Full Text]
Jacobs, E. T, Lanza, E., Alberts, D. S, Hsu, C.-H., Jiang, R., Schatzkin, A., Thompson, P. A, Martinez, M. E.
(2006). Fiber, sex, and colorectal adenoma: results of a pooled analysis. Am. J. Clin. Nutr.
83: 343-349
[Abstract][Full Text]
Park, Y., Hunter, D. J., Spiegelman, D., Bergkvist, L., Berrino, F., van den Brandt, P. A., Buring, J. E., Colditz, G. A., Freudenheim, J. L., Fuchs, C. S., Giovannucci, E., Goldbohm, R. A., Graham, S., Harnack, L., Hartman, A. M., Jacobs, D. R. Jr, Kato, I., Krogh, V., Leitzmann, M. F., McCullough, M. L., Miller, A. B., Pietinen, P., Rohan, T. E., Schatzkin, A., Willett, W. C., Wolk, A., Zeleniuch-Jacquotte, A., Zhang, S. M., Smith-Warner, S. A.
(2005). Dietary Fiber Intake and Risk of Colorectal Cancer: A Pooled Analysis of Prospective Cohort Studies. JAMA
294: 2849-2857
[Abstract][Full Text]
Michels, K. B., Fuchs, C. S., Giovannucci, E., Colditz, G. A., Hunter, D. J., Stampfer, M. J., Willett, W. C.
(2005). Fiber Intake and Incidence of Colorectal Cancer among 76,947 Women and 47,279 Men. Cancer Epidemiol. Biomarkers Prev.
14: 842-849
[Abstract][Full Text]
Mizoue, T., Yamaji, T., Tabata, S., Yamaguchi, K., Shimizu, E., Mineshita, M., Ogawa, S., Kono, S.
(2005). Dietary Patterns and Colorectal Adenomas in Japanese Men: The Self-Defense Forces Health Study. Am J Epidemiol
161: 338-345
[Abstract][Full Text]
Roberts, C. K., Barnard, R. J.
(2005). Effects of exercise and diet on chronic disease. J. Appl. Physiol.
98: 3-30
[Abstract][Full Text]
Barnard, R. J.
(2004). Prevention of Cancer Through Lifestyle Changes. Evid Based Complement Alternat Med
1: 233-239
[Abstract][Full Text]
Yuan, H., Liddle, F. J., Mahajan, S., Frank, D. A.
(2004). IL-6-induced survival of colorectal carcinoma cells is inhibited by butyrate through down-regulation of the IL-6 receptor. Carcinogenesis
25: 2247-2255
[Abstract][Full Text]
Papas, M. A., Giovannucci, E., Platz, E. A.
(2004). Fiber from Fruit and Colorectal Neoplasia. Cancer Epidemiol. Biomarkers Prev.
13: 1267-1270
[Full Text]
Chamberlain, K.
(2004). Food and Health: Expanding the Agenda for Health Psychology. J Health Psychol
9: 467-481
[Abstract]
Tsao, A. S., Kim, E. S., Hong, W. K.
(2004). Chemoprevention of Cancer. CA Cancer J Clin
54: 150-180
[Abstract][Full Text]
Nakaji, S., Ishiguro, S., Iwane, S., Ohta, M., Sugawara, K., Sakamoto, J., Fukuda, S.
(2004). The Prevention of Colon Carcinogenesis in Rats by Dietary Cellulose Is Greater than the Promotive Effect of Dietary Lard as Assessed by Repeated Endoscopic Observation. J. Nutr.
134: 935-939
[Abstract][Full Text]
Lupton, J. R.
(2004). Microbial Degradation Products Influence Colon Cancer Risk: the Butyrate Controversy. J. Nutr.
134: 479-482
[Abstract][Full Text]
Dyer, K.J., Fearon, K C H, Buckner, K., Richardson, R.A.
(2004). Diet and colorectal cancer risk: Baseline dietary knowledge of colorectal patients. Health Education Journal
63: 242-253
[Abstract]
Erhardt, J. G, Meisner, C., Bode, J C., Bode, C.
(2003). Lycopene, {beta}-carotene, and colorectal adenomas. Am. J. Clin. Nutr.
78: 1219-1224
[Abstract][Full Text]
Satia-Abouta, J., Galanko, J. A., Potter, J. D., Ammerman, A., Martin, C. F., Sandler, R. S.
(2003). Associations of Total Energy and Macronutrients with Colon Cancer Risk in African Americans and Whites: Results from the North Carolina Colon Cancer Study. Am J Epidemiol
158: 951-962
[Abstract][Full Text]
Kipnis, V., Subar, A. F., Midthune, D., Freedman, L. S., Ballard-Barbash, R., Troiano, R. P., Bingham, S., Schoeller, D. A., Schatzkin, A., Carroll, R. J.
(2003). Structure of Dietary Measurement Error: Results of the OPEN Biomarker Study. Am J Epidemiol
158: 14-21
[Abstract][Full Text]
Mai, V., Flood, A., Peters, U., Lacey, J. V Jr, Schairer, C., Schatzkin, A.
(2003). Dietary fibre and risk of colorectal cancer in the Breast Cancer Detection Demonstration Project (BCDDP) follow-up cohort. Int J Epidemiol
32: 234-239
[Abstract][Full Text]
Lawlor, D. A, Ness, A. R
(2003). Commentary: The rough world of nutritional epidemiology: Does dietary fibre prevent large bowel cancer?. Int J Epidemiol
32: 239-243
[Full Text]
Butler, L. M., Sinha, R., Millikan, R. C., Martin, C. F., Newman, B., Gammon, M. D., Ammerman, A. S., Sandler, R. S.
(2003). Heterocyclic Amines, Meat Intake, and Association with Colon Cancer in a Population-based Study. Am J Epidemiol
157: 434-445
[Abstract][Full Text]
Fung, T., Hu, F. B., Fuchs, C., Giovannucci, E., Hunter, D. J., Stampfer, M. J., Colditz, G. A., Willett, W. C.
(2003). Major Dietary Patterns and the Risk of Colorectal Cancer in Women. Arch Intern Med
163: 309-314
[Abstract][Full Text]
Hamill, F. A.
(2002). Colon Cancer and the Western Diet. Integr Cancer Ther
1: 420-424
McCullough, M. L, Feskanich, D., Stampfer, M. J, Giovannucci, E. L, Rimm, E. B, Hu, F. B, Spiegelman, D., Hunter, D. J, Colditz, G. A, Willett, W. C
(2002). Diet quality and major chronic disease risk in men and women: moving toward improved dietary guidance. Am. J. Clin. Nutr.
76: 1261-1271
[Abstract][Full Text]
Mitchell, R. J., Farrington, S. M., Dunlop, M. G., Campbell, H.
(2002). Mismatch Repair Genes hMLH1 and hMSH2 and Colorectal Cancer: A HuGE Review. Am J Epidemiol
156: 885-902
[Abstract][Full Text]
Jacobs, E. T., Giuliano, A. R., Roe, D. J., Guillen-Rodriguez, J. M., Alberts, D. S., Martinez, M. E.
(2002). Baseline Dietary Fiber Intake and Colorectal Adenoma Recurrence in the Wheat Bran Fiber Randomized Trial. JNCI J Natl Cancer Inst
94: 1620-1625
[Abstract][Full Text]
Jacobs, E. T., Giuliano, A. R., Roe, D. J., Guillen-Rodriguez, J. M., Hess, L. M., Alberts, D. S., Martinez, M. E.
(2002). Intake of Supplemental and Total Fiber and Risk of Colorectal Adenoma Recurrence in the Wheat Bran Fiber Trial. Cancer Epidemiol. Biomarkers Prev.
11: 906-914
[Abstract][Full Text]
Wacker, M., Wanek, P., Eder, E., Hylla, S., Gostner, A., Scheppach, W.
(2002). Effect of Enzyme-resistant Starch on Formation of 1,N2-Propanodeoxyguanosine Adducts of trans-4-Hydroxy-2-nonenal and Cell Proliferation in the Colonic Mucosa of Healthy Volunteers. Cancer Epidemiol. Biomarkers Prev.
11: 915-920
[Abstract][Full Text]
Wolter, F., Stein, J.
(2002). Resveratrol Enhances the Differentiation Induced by Butyrate in Caco-2 Colon Cancer Cells. J. Nutr.
132: 2082-2086
[Abstract][Full Text]
Fenton, J. I., Wolff, M. S., Orth, M. W., Hord, N. G.
(2002). Membrane-type matrix metalloproteinases mediate curcumin-induced cell migration in non-tumorigenic colon epithelial cells differing in Apc genotype. Carcinogenesis
23: 1065-1070
[Abstract][Full Text]
Emenaker, N. J., Calaf, G. M., Cox, D., Basson, M. D., Qureshi, N.
(2001). Short-Chain Fatty Acids Inhibit Invasive Human Colon Cancer by Modulating uPA, TIMP-1, TIMP-2, Mutant p53, Bcl-2, Bax, p21 and PCNA Protein Expression in an In Vitro Cell Culture Model. J. Nutr.
131: 3041S-3046
[Abstract][Full Text]
Gerber, M.
(2001). The Comprehensive Approach to Diet: A Critical Review. J. Nutr.
131: 3051S-3055
[Abstract][Full Text]
Giovannucci, E.
(2001). Insulin, Insulin-Like Growth Factors and Colon Cancer: A Review of the Evidence. J. Nutr.
131: 3109S-3120
[Abstract][Full Text]
Normen, A L., Brants, H. A., Voorrips, L. E, Andersson, H. A, van den Brandt, P. A, Goldbohm, R A.
(2001). Plant sterol intakes and colorectal cancer risk in the Netherlands Cohort Study on Diet and Cancer. Am. J. Clin. Nutr.
74: 141-148
[Abstract][Full Text]
Topping, D. L., Clifton, P. M.
(2001). Short-Chain Fatty Acids and Human Colonic Function: Roles of Resistant Starch and Nonstarch Polysaccharides. Physiol. Rev.
81: 1031-1064
[Abstract][Full Text]
Michels, K. B., Giovannucci, E., Feskanich, D., Willett, W. C.
(2001). Response. JNCI J Natl Cancer Inst
93: 791-791
[Full Text]
Sandhu, M. S., White, I. R., McPherson, K.
(2001). Systematic Review of the Prospective Cohort Studies on Meat Consumption and Colorectal Cancer Risk: A Meta-Analytical Approach. Cancer Epidemiol. Biomarkers Prev.
10: 439-446
[Abstract][Full Text]
Terry, P., Giovannucci, E., Michels, K. B., Bergkvist, L., Hansen, H., Holmberg, L., Wolk, A.
(2001). Fruit, Vegetables, Dietary Fiber, and Risk of Colorectal Cancer. JNCI J Natl Cancer Inst
93: 525-533
[Abstract][Full Text]
Sano, T., Sasako, M.
(2001). Green Tea and Gastric Cancer. NEJM
344: 675-676
[Full Text]
Kipnis, V., Midthune, D., Freedman, L. S., Bingham, S., Schatzkin, A., Subar, A., Carroll, R. J.
(2001). Empirical Evidence of Correlated Biases in Dietary Assessment Instruments and Its Implications. Am J Epidemiol
153: 394-403
[Abstract][Full Text]
Zhu, W.-G., Lakshmanan, R. R., Beal, M. D., Otterson, G. A.
(2001). DNA Methyltransferase Inhibition Enhances Apoptosis Induced by Histone Deacetylase Inhibitors. Cancer Res.
61: 1327-1333
[Abstract][Full Text]
Willett, W. C.
(2001). Diet and Cancer: One View at the Start of the Millennium. Cancer Epidemiol. Biomarkers Prev.
10: 3-8
[Abstract][Full Text]
Perrin, P, Pierre, F, Patry, Y, Champ, M, Berreur, M, Pradal, G, Bornet, F, Meflah, K, Menanteau, J
(2001). Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats. Gut
48: 53-61
[Abstract][Full Text]
Voorrips, L. E., Goldbohm, R. A., van Poppel, G., Sturmans, F., Hermus, R. J. J., van den Brandt, P. A.
(2000). Vegetable and Fruit Consumption and Risks of Colon and Rectal Cancer in a Prospective Cohort Study The Netherlands Cohort Study on Diet and Cancer. Am J Epidemiol
152: 1081-1092
[Abstract][Full Text]
Michels, K. B., Edward Giovannucci, , Joshipura, K. J., Rosner, B. A., Stampfer, M. J., Fuchs, C. S., Colditz, G. A., Speizer, F. E., Willett, W. C.
(2000). Prospective Study of Fruit and Vegetable Consumption and Incidence of Colon and Rectal Cancers. JNCI J Natl Cancer Inst
92: 1740-1752
[Abstract][Full Text]
Willett, W. C.
(2000). Diet and Cancer. The Oncologist
5: 393-404
[Abstract][Full Text]
Reddy, B. S., Hirose, Y., Cohen, L. A., Simi, B., Cooma, I., Rao, C. V.
(2000). Preventive Potential of Wheat Bran Fractions against Experimental Colon Carcinogenesis: Implications for Human Colon Cancer Prevention. Cancer Res.
60: 4792-4797
[Abstract][Full Text]
Gråsten, S. M., Juntunen, K. S., Poutanen, K. S., Gylling, H. K., Miettinen, T. A., Mykkänen, H. M.
(2000). Rye Bread Improves Bowel Function and Decreases the Concentrations of Some Compounds That Are Putative Colon Cancer Risk Markers in Middle-Aged Women and Men. J. Nutr.
130: 2215-2221
[Abstract][Full Text]
Janne, P. A., Mayer, R. J.
(2000). Chemoprevention of Colorectal Cancer. NEJM
342: 1960-1968
[Full Text]
McKean-Cowdin, R., Feigelson, H. S., Ross, R. K., Pike, M. C., Henderson, B. E.
(2000). Declining Cancer Rates in the 1990s. JCO
18: 2258-2268
[Abstract][Full Text]
Slavin, J. L.
(2000). Mechanisms for the Impact of Whole Grain Foods on Cancer Risk. J. Am. Coll. Nutr.
19: 300S-307
[Abstract][Full Text]
Jacobs, D. R. Jr, Pereira, M. A., Meyer, K. A., Kushi, L. H.
(2000). Fiber from Whole Grains, but not Refined Grains, Is Inversely Associated with All-Cause Mortality in Older Women: The Iowa Women's Health Study. J. Am. Coll. Nutr.
19: 326S-330
[Abstract][Full Text]
Schatzkin, A., Lanza, E., Corle, D., Lance, P., Iber, F., Caan, B., Shike, M., Weissfeld, J., Burt, R., Cooper, M. R., Kikendall, J. W., Cahill, J., Freedman, L., Marshall, J., Schoen, R. E., Slattery, M., The Polyp Prevention Trial Study Group,
(2000). Lack of Effect of a Low-Fat, High-Fiber Diet on the Recurrence of Colorectal Adenomas. NEJM
342: 1149-1155
[Abstract][Full Text]
Alberts, D. S., Martinez, M. E., Roe, D. J., Guillen-Rodriguez, J. M., Marshall, J. R., van Leeuwen, J. B., Reid, M. E., Ritenbaugh, C., Vargas, P. A., Bhattacharyya, A.B., Earnest, D. L., Sampliner, R. E., Parish, D., Koonce, K., Fales, L., The Phoenix Colon Cancer Prevention Physicians' Ne,
(2000). Lack of Effect of a High-Fiber Cereal Supplement on the Recurrence of Colorectal Adenomas. NEJM
342: 1156-1162
[Abstract][Full Text]
Reddy, B. S.
(2000). Novel Approaches to the Prevention of Colon Cancer by Nutritional Manipulation and Chemoprevention. Cancer Epidemiol. Biomarkers Prev.
9: 239-247
[Abstract][Full Text]
MARIC, R, CHENG;, K K, LAGERGREN, J, NYREN, P
(2000). Association between colon cancer and adenocarcinoma of the oesophagus • Reply. Gut
46: 293a-293
[Full Text]
Kien, C. L., Chang, J. C., Cooper, J. R.
(2000). Butyric Acid Is Synthesized by Piglets. J. Nutr.
130: 234-237
[Abstract][Full Text]
Augenlicht, L. H., Anthony, G. M., Church, T. L., Edelmann, W., Kucherlapati, R., Yang, K., Lipkin, M., Heerdt, B. G.
(1999). Short-Chain Fatty Acid Metabolism, Apoptosis, and Apc-initiated Tumorigenesis in the Mouse Gastrointestinal Mucosa. Cancer Res.
59: 6005-6009
[Abstract][Full Text]
Nixon, D.
(1999). Alternative and Complementary Therapies in Oncology Care. JCO
17: 35-37
[Full Text]
Newmark, H., Wittkowski, K. M., Shiff, S. J., Hirsch, J., Holmes, M. D., Rosner, B., Willett, W. C.
(1999). Dietary Fat and Risk of Breast Cancer. JAMA
282: 1223-1224
[Full Text]
Martínez, M. E., Marshall, J. R., Graver, E., Whitacre, R. C., Woolf, K., Ritenbaugh, C., Alberts, D. S.
(1999). Reliability and Validity of a Self-Administered Food Frequency Questionnaire in a Chemoprevention Trial of Adenoma Recurrence. Cancer Epidemiol. Biomarkers Prev.
8: 941-946
[Abstract][Full Text]
Pierre, F., Perrin, P., Bassonga, E., Bornet, F., Meflah, K., Menanteau, J.
(1999). T cell status influences colon tumor occurrence in Min mice fed short chain fructo-oligosaccharides as a diet supplement. Carcinogenesis
20: 1953-1956
[Abstract][Full Text]
Hallfrisch, J., Behall, K. M.
(1999). Breath Hydrogen and Methane Responses of Men and Women to Breads Made with White Flour or Whole Wheat Flours of Different Particle Sizes. J. Am. Coll. Nutr.
18: 296-302
[Abstract][Full Text]
Garner, C. M.
(1999). Dietary fibre intake was not associated with a lower risk of colorectal cancer in women. Evid. Based Nurs.
2: 89-89
[Full Text]
Ravin, N. D., Mohandas, K.M., Cummings, J. H., Southgate, D. A.T., Heaton, K. W., Lewis, S. J., Madar, Z., Stark, A., Camire, M. E., Fuchs, C. S., Willett, W. C.
(1999). Dietary Fiber and Colorectal Cancer. NEJM
340: 1924-1926
[Full Text]
Potter, J. D.
(1999). Colorectal Cancer: Molecules and Populations. JNCI J Natl Cancer Inst
91: 916-932
[Abstract][Full Text]
Levin, B.
(1999). Colorectal Cancer Screening: Sifting Through the Evidence. JNCI J Natl Cancer Inst
91: 399-400
[Full Text]
Temple, R.
(1999). Meta-analysis and Epidemiologic Studies in Drug Development and Postmarketing Surveillance. JAMA
281: 841-844
[Full Text]
(1999). Does Dietary Fiber Reduce Risk for Colorectal Cancer?. Journal Watch Dermatology
1999: 13-13
[Full Text]
(1999). Dietary Fiber Healthful, But Doesn't Prevent Colon Cancer. JWatch Women's Health
1999: 14-14
[Full Text]
(1999). Does Dietary Fiber Reduce Risk for Colorectal Cancer?. JWatch General
1999: 2-2
[Full Text]
Potter, J. D.
(1999). Fiber and Colorectal Cancer -- Where to Now?. NEJM
340: 223-224
[Full Text]
