NCI medNews

"Prevention of colorectal cancer" is redistributed by University of Bonn, Medical Center

Prevention of colorectal cancer

208/04731

Get this document via a secure connection

Summary Of Evidence
Significance
Evidence Of Benefit

CancerMail from the National Cancer Institute

###########################################################################

!!! ATTENTION !!!

The National Cancer Institute (NCI) has updated its cancer information delivery services. In the future, please use the Cancer.gov web site (Http: //cancer.gov/) to meet your cancer information needs. CancerMail users in the United States can obtain cancer information by telephone at 1-800-4-CANCER (1-800-422-6237).

The NCI will no longer support CancerMail after November 2002. If you have comments about the NCI's cancer information delivery services, contact us by e-mail at cancer.govstaff@mail.nih.gov or call 301-496-9096.

###########################################################################

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Information from PDQ -- for Health Professionals

SUMMARY OF EVIDENCE

Note: Separate PDQ summaries on Screening for Colorectal Cancer; Colon Cancer Treatment; and Rectal Cancer Treatment are also available.

High Fat Diet

Epidemiologic, experimental (animal), and clinical investigations suggest that diets high in total fat, protein, calories, alcohol, and meat (both red and white) and low in calcium and folate, are associated with an increased incidence of colorectal cancer.

Levels of Evidence:

3aii: Evidence obtained from well-designed and conducted cohort or case-control analytic studies, preferably from more than one center or research group, that have a cancer incidence endpoint

4aii: Ecologic (descriptive) studies that have a cancer incidence endpoint

Fiber, Fruits, and Vegetables

Cereal fiber supplementation and diets low in fat and high in fiber, fruits, and vegetables, however, do not reduce the rate of adenoma recurrence over a 3-year to 4-year period.

Level of Evidence:

1b: Evidence obtained from at least one well-designed and conducted randomized controlled trial that has a generally accepted intermediate endpoint (adenomatous polyps) for studies of colorectal cancer prevention

Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs including piroxicam, sulindac and aspirin may prevent adenoma formation or cause adenomatous polyps to regress in the setting of familial adenomatous polyposis.

Levels of Evidence:

1b: Evidence obtained from at least one well-designed and conducted randomized controlled trial that has a generally accepted intermediate endpoint (adenomatous polyps) for studies of colorectal cancer prevention

3ai,3aii: Evidence obtained from well-designed and conducted cohort or case-control analytic studies, preferably from more than one center or research group that have cancer mortality and cancer incidence endpoints

Cigarette Smoking

Cigarette smoking is associated with an increased tendency to form adenomas and develop colorectal cancer.

Level of Evidence:

3aii: Evidence obtained from well-designed and conducted cohort or case-control analytic studies, preferably from more than one center or research group that have a cancer incidence endpoint

Postmenopausal Hormone Use

Postmenopausal female hormone use is associated with a decreased risk of colon cancer but not rectal cancer.

Level of evidence:

3aii: Evidence obtained from well-designed and conducted cohort or case-control analytic studies, preferably from more than one center or research group with a cancer incidence endpoint

Colonoscopy

Colonoscopy with removal of adenomatous polyps may reduce the risk of colorectal cancer.

Level of Evidence:

3ai: Evidence obtained from well-designed and conducted cohort or case-control analytic studies, preferably from more than one center or research group that have a cancer mortality endpoint

SIGNIFICANCE

Incidence and Mortality

Colorectal cancer is the third most common malignant neoplasm worldwide [1] and the second leading cause of cancer deaths (irrespective of gender) in the United States.[2] It is estimated that there will be 148,300 new cases and 56,600 deaths in the United States in 2002. Between 1973 and 1995, mortality from colorectal cancer declined by 20.8% and incidence declined by 7.4% in the United States. The overall 5-year survival rate is 62.1%. About 6% of Americans are expected to develop the disease within their lifetime.[3] The risk of colorectal cancer begins to increase after the age of 40 and rises sharply at the ages of 50 to 55; the risk doubles with each succeeding decade, and continues to rise exponentially. Despite advances in surgical technique and adjuvant therapy, there has been only a modest improvement in survival for patients who present with advanced neoplasms.[4,5] Hence, effective primary and secondary preventive approaches must be developed to reduce the morbidity and mortality from colorectal cancer.

Definition of Prevention

Primary prevention involves the identification of genetic, biologic, and environmental factors that are etiologic or pathogenic in the development of cancer, and subsequent complete or significant interference with their effects on carcinogenesis. Removal of premalignant lesions (adenomas) may also be an effective form of primary prevention.

Etiology and Pathogenesis of Colorectal Cancer

Genetics,[6,7] experimental,[8,9] and epidemiologic [10,11] studies suggest that colorectal cancer results from complex interactions between inherited susceptibility and environmental factors. It has been suggested that dietary factors may be responsible for a significant but poorly quantitated number of cancer cases.[12] Efforts to identify causes and to develop effective preventive measures have led to the hypothesis that adenomatous polyps (adenomas) are precursors for the vast majority of colorectal cancers.[13] While most of these adenomas are polypoid, flat and depressed lesions may be more prevalent than previously recognized. Large flat and depressed lesions are more likely to be severely dysplastic. Specialized techniques may be needed to identify, biopsy, and remove such lesions.[14] In effect, measures which reduce the incidence and prevalence of adenomas may result in a subsequent decrease in the risk of colorectal cancer.[15] The finding of an adenoma on flexible sigmoidoscopy may warrant colonoscopy to evaluate the more proximal colon for synchronous neoplasms.[16] Many of the intervention trials employ adenoma recurrence or disappearance as a surrogate end point.[17] The evolution of a carcinoma from a small adenoma, however, takes many years.[10]

References:

  1. Shike M, Winawer SJ, Greenwald PH, et al.: Primary prevention of colorectal cancer: the WHO Collaborating Centre for the Prevention of Colorectal Cancer. Bulletin of the World Health Organization 68(3): 377-385, 1990.
  2. American Cancer Society: Cancer Facts and Figures-2002. Atlanta, Ga: American Cancer Society, 2002.
  3. Ries LA, Kosary CL, Hankey BF, et al., eds.: SEER Cancer Statistics Review 1973-1995. Bethesda, Md: National Cancer Institute, 1998.
  4. Moertel CG, Fleming TR, Macdonald JS, et al.: Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. New England Journal of Medicine 322(6): 352-358, 1990.
  5. Krook JE, Moertel CG, Gunderson LL, et al.: Effective surgical adjuvant therapy for high-risk rectal carcinoma. New England Journal of Medicine 324(11): 709-715, 1991.
  6. Willett W: The search for the causes of breast and colon cancer. Nature 338(6214): 389-394, 1989.
  7. Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61(5): 759-767, 1990.
  8. Reddy B, Engle A, Katsifis S, et al.: Biochemical epidemiology of colon cancer: effect of types of dietary fiber on fecal mutagens, acid, and neutral sterols in healthy subjects. Cancer Research 49(16): 4629-4635, 1989.
  9. Reddy BS, Tanaka T, Simi B: Effect of different levels of dietary trans fat or corn oil on azoxymethane-induced colon carcinogenesis in F344 rats. Journal of the National Cancer Institute 75(4): 791-798, 1985.
  10. Potter JD: Reconciling the epidemiology, physiology, and molecular biology of colon cancer. JAMA: Journal of the American Medical Association 268(12): 1573-1577, 1992.
  11. Wynder EL, Reddy BS: Dietary fat and fiber and colon cancer. Seminars in Oncology 10(3): 264-272, 1983.
  12. Doll R, Peto R: The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. Journal of the National Cancer Institute 66(6): 1191-1308, 1981.
  13. Hill MJ, Morson BC, Bussey HJ: Aetiology of adenoma--carcinoma sequence in large bowel. Lancet 1(8058): 245-247, 1978.
  14. Rembacken BJ, Fujii T, Cairns A, et al.: Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK. Lancet 355(9211): 1211-1214, 2000.
  15. Winawer SJ, Zauber AG, Ho MN, et al. for the National Polyp Study Workgroup: Prevention of colorectal cancer by colonoscopic polypectomy. New England Journal of Medicine 329(27): 1977-1981, 1993.
  16. Read TE, Read JD, Butterly LF: Importance of adenomas 5 mm or less in diameter that are detected by sigmoidoscopy. New England Journal of Medicine 336(1): 8-12, 1997.
  17. Vargas PA, Alberts DS: Colon cancer: the quest for prevention. Oncology (Huntington NY) 7(11 suppl): 33-40, 1993.

EVIDENCE OF BENEFIT

Dietary Factors

The studies reviewed below include those on adenomas; special note is made if a study applies to adenomas only.

Dietary Fat and Meat Intake

Colon cancer rates are high in populations with high total fat intakes and are lower in those consuming less fat.[1] On average, fat comprises 40% to 45% of total caloric intake in high-incidence Western countries; in low-risk populations fat accounts for only 10% of dietary calories.[2] In laboratory studies a high fat intake increases the incidence of induced colon tumors in experimental animals.[3,4] Several case-control studies have explored the association of colon cancer risk with meat or fat consumption as well as protein and energy intake.[5,6] Although positive associations with meat consumption or with fat intake have been found frequently, the results have not always achieved statistical significance.[7] A number of prospective cohort studies have been conducted in the United States and abroad. In Japan, an increased risk of colon cancer with increased frequency of meat consumption was observed in the group with infrequent vegetable consumption among a group of 265,000 men and women.[8] In Norway, an increased risk for processed meat only was found,[9] a finding that was confirmed in the Netherlands.[10] A clearly defined gradient in risk for frequency of meat and poultry consumption was not observed in a population of Seventh Day Adventists that included a large proportion of vegetarians.[11] A prospective study among female nurses showed an increased risk of colon cancer associated with red meat consumption (beef, pork, lamb, and processed meat) and also with the intake of saturated and monounsaturated fat, predominantly derived from animals.[12] No increase in risk with meat or fat consumption was seen, however, in 2 other large prospective studies, the American Cancer Society's Cancer Prevention Study II and the Iowa Women's Health Study.[13,14] In a prospective cohort study of a low-risk population of non-Hispanic white members of the Adventist Health Study, a positive association between meat (both red and white) intake and colon cancer was observed (relative risk for greater than or equal to 1 time per week versus no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87, p for trend = 0.01).[15] It has been hypothesized that the heterocyclic amines (HCAs) formed when meat and fish are cooked at high temperatures may contribute to the increased risk of colorectal cancers associated with meat consumption that has been observed in epidemiologic studies. A population-based case-control study in Sweden, however, found no evidence of increased risk associated with total HCA intake; for colon cancer the relative risk was 0.6 (95% CI 0.4-1.0), and for rectal cancer it was 0.7 (95% CI 0.4-1.1).[16,17]

Explanations for the conflicting results regarding whether dietary fat or meat intake affects risk of colorectal cancer [10] include, (a) validity of dietary questionnaires used; (b) differences in the average age of the population studied; (c) variations in methods of meat preparation (in some instances, mutagenic and carcinogenic heterocyclic amines could have been released at high temperatures [18]) and (d) variability in the consumption of other foods, such as vegetables.[19] In addition, some epidemiological studies have reported lower incidence rates of colon cancer in populations with high intakes of both fat and fiber, compared with populations with high levels of fat but low levels of fiber consumption.[20] Although far from clear cut, the available evidence suggests colorectal cancer risk is possibly associated with some interaction of dietary fat and protein and caloric intake.

Six case-control studies and 2 cohort studies have explored potential dietary risk factors for colorectal adenomas.[21,22] Three of the 8 studies found that higher fat consumption was associated with increased risk. High fat intake has been found to increase the risk of adenoma recurrence following polypectomy.[23] In a multicenter randomized, controlled trial, a diet low in fat (20% of total calories) and high in fiber and fruits and vegetables did not reduce the risk of recurrence of colorectal adenomas.[24]

Bile Acids

A central effect of bile acids in the etiology and pathogenesis of colorectal cancer has been claimed.[25] An increased bile acid concentration in the intestinal tract accompanies a high-fat diet since bile acids are released from the gallbladder after fat ingestion. The concentration of bile acids in the colon is heavily influenced by the amount and type of fat in the diet.[26] The potential mechanism of action of bile salts in colorectal carcinogenesis is unknown, although it has been suggested that it is mediated by diacylglycerol.[27] The conversion of dietary phospholipids to diacylglycerol by intestinal bacteria is enhanced by a high-fat diet. It is proposed that diacylglycerol enters the cell directly, stimulating protein kinase C which is involved in intracellular signal transduction.

Dietary Fiber, Vegetables, and Fruit

The evidence on whether dietary fiber exerts a protective role in reducing the incidence of colorectal cancer is mixed. Most animal and epidemiologic studies show a protective effect of dietary fiber on colon carcinogenesis.[28] The term fiber is used to describe a complex mixture of compounds including insoluble fiber (typified by wheat bran and cellulose) and soluble fiber (usually dried beans). Ingestion of fiber could modify carcinogenesis in the large bowel by a number of potential mechanisms.[29-31] These mechanisms include binding to bile acids, increasing fecal water and possibly diluting carcinogens, and decreasing transit time (not an obvious factor). Fiber may act as a substrate for bacterial fermentation with a resultant increase in bacterial mass and the production of short chain fatty acids, typified by butyrate.[31] Butyrate has been shown to have anticarcinogenic effects in vitro and is regarded as an important fuel for the colonic epithelium.[32,33] A meta-analysis of 13 case-control studies from 9 countries concluded that intake of fiber-rich foods is inversely related to cancers of both colon and rectum.[34] The analysis did not include fiber supplements. The inverse association with fiber was observed in 12 of the 13 studies and was similar in magnitude for left-sided and right-sided colon and rectal cancers, for men and for women, and for different age groups. It has been suggested that the inverse association with fiber may be reflective of some other closely associated dietary constituents, such as the anticarcinogens found in vegetables, fruits, legumes, nuts and grains.[5,34] These substances include phenolic compounds, sulfur-containing compounds and flavones.[35,36] In a prospective cohort study of a low-risk population, an inverse association was found with legume intake and the risk of colorectal cancer (relative risk for greater than 2 times per week versus 1 time per week = 0.53, 95% CI 0.33-0.86, p for trend = 0.03).[15]

Other studies have corroborated the effects of dietary fiber. One study used a supplement of 10 g/day of wheat bran, cellulose and oat bran, and found a decreased mutagenic activity of fecal contents in those receiving wheat bran and cellulose supplementation.[37] Although, no measurable inhibition was observed during oat bran supplementation. Fecal total and secondary bile acid excretion increased during oat fiber supplementation.

Despite the evidence from case-control studies of a protective effect, results from the large prospective Nurses' Health Study found no difference in risk of colorectal cancer between women in the highest compared to lowest quintile group with respect to dietary fiber, after adjusting for age, known risk factors, and total energy intake (relative risk = 0.95; 95% CI 0.73-1.25).[38]

Many epidemiologic studies have examined the relationship between fruit and vegetable intake and the incidence of colon and/or rectal cancer,[39] with considerable variation in findings. Perhaps the most definitive analysis to date is a prospective study that examined dietary intake data based on food frequency questionnaires from 88,764 women in the Nurses Health Study and 47,325 men in the Health Professionals Follow-up Study.[40] The study included a total of 1,743,645 person-years of follow-up, 937 cases of colon cancer, and 244 cases of rectal cancer. Based on analyses adjusted for numerous covariates, the authors found no association in women or men between overall fruit and vegetable consumption and risk of colon or rectal cancer. Neither were associations observed when the data were examined for subgroups of fruits or vegetables (with the exception of legumes, which were associated with an increased risk of colon cancer in women) or individual fruits or vegetables (with the exception of prunes, which were associated with an increased risk of colon cancer in men). Results did not change when data were examined by vitamin use status, smoking status, or family history of colorectal cancer, nor were elevated risks seen when individuals with very low levels of fruit and vegetable consumption were compared to those with the highest levels. For women and men combined, the covariate-adjusted relative risk of colon cancer associated with one additional serving of fruits and vegetables per day was 1.02 (95% CI 0.98-1.05); the comparable relative risk for rectal cancer was 1.02 (95% CI 0.95-1.09).

In a population-based prospective cohort study of 61,463 women in Sweden, individuals who consumed very low amounts of fruits and vegetables (less than 1.5 servings of fruit and vegetables per day) had a relative risk for developing colorectal cancer of 1.65 (95% CI 1.23 - 2.2, p trend = 0.001) as compared with those individuals who consumed greater than 2.5 servings. However, there was little evidence of a benefit for higher as compared with moderate consumption (greater than versus less than 3.5 servings). Limitations of this study are that dietary intake during the study period was not reassessed over time and the influence of physical activity could not be accurately determined. In addition, the conclusion about very low amounts of intake of fruits and vegetables is based on a retrospective subdivision of the lowest quartile of consumption and its strength has not been adjusted for other potential confounding factors.[41]

Six case-control studies and 3 cohort studies have explored potential dietary risk factors for colorectal adenomas.[21,22,38] Four of the 9 found an association of fiber, carbohydrates and/or vegetables with reduced risk. In one study, cases with moderate or severe dysplasia had a significantly lower intake of cruciferous vegetables than those with mild dysplasia. No significant effect of dietary fiber on colorectal adenoma was found in the large cohort study of U.S. nurses.[38]

Other studies in progress or nearing completion are listed in Table 1.[28] High fiber cereal supplements over a 3-year period did not result in a decrease in adenoma recurrence in a randomized, controlled trial of 1,303 individuals.[42] In a multicenter randomized, controlled trial, a diet low in fat (20% of total calories), high in fiber (18 g of dietary fiber per 1,000 kcal) and fruits and vegetables (3.5 servings per 1,000 kcal) was not associated with a reduction in risk of recurrence of colorectal adenomas.[24] 

         Table 1: Ongoing Phase III Trials of New Strategies to Prevent
                  the Recurrence of Non-Familial Colorectal Adenomas [28]

-------------------------------------------------------------------------------
Investigator/    Patient            Randomized           Status of Patient
Institution      Population         Agent                Accrual
-------------------------------------------------------------------------------
D Alberts        Non-Familial       High vs low wheat    Completed
U of Arizona     polyps             bran fiber

J Baron          Non-Familial       Calcium vs placebo   Completed
(Multicenter)    polyps
Dartmouth Univ

J Baron          Non-Familial       Aspirin vs placebo   Ongoing
(Multicenter)    polyps
Dartmouth Univ

R Greenberg      Non-Familial       Factorial: Vit C,    Completed
(Multicenter)    polyps             betacarotene, Vit E
Dartmouth Univ

I Macrae         Non-Familial       Factorial: low       Completed
Melbourne        polyps              fat/high fiber/
                                    betacarotene

A Schatzkin      Non-Familial       Low fat/high in      Completed
(Multicenter)    polyps             fiber, fruits,
NCI                                 and vegetables

Calcium

It has been hypothesized that orally ingested calcium lowers colon cancer risk by binding bile acids and fatty acids, thereby reducing exposure to toxic intraluminal compounds.[43] Indirect effects on bile acid metabolism and a direct effect on colonic epithelial cells are also possible.

Several [44-47] but not all [22,48] epidemiologic studies have observed an inverse relationship between calcium intake and cancer risk. Interpretation of these studies can be quite complex. For example, in Utah, an inverse relationship between colon cancer and calcium was observed in a study that compared members of the Church of Jesus Christ of Latter-Day Saints (Mormons) and Seventh Day Adventists with a group from the U.S. population at large. Both study groups have higher calcium intakes, mainly milk and dairy products, than the national average. Unlike the Seventh Day Adventists, however, the Mormon group had a consumption of meats and fat similar to that of the general population.

Experimental studies in rodents [49] and some but not all [50-53] human studies have described a decrease in colonic epithelial cell proliferation after the administration of calcium citrate. Human studies using labeling index are dependent on a complex methodology.[54] A randomized placebo-controlled trial tested the effect of calcium supplementation (3 g calcium carbonate daily (1200 mg elemental calcium)) on the risk of recurrent adenoma.[55] The primary endpoint was the proportion of subjects (72% of whom were male) in whom at least 1 adenoma was detected following a first and/or second follow-up endoscopy. A modest decrease in risk was found for both developing at least 1 recurrent adenoma (adjusted risk ratio = 0.81, 95% CI 0.67-0.99) and in the average number of adenomas (adjusted risk ratio = 0.76, 95% CI 0.60-0.96). The investigators found the effect of calcium was similar across age, sex, and baseline dietary intake categories of calcium, fat, or fiber. The study was limited to individuals with a recent history of colorectal adenomas and so could not determine the effect of calcium on risk of first adenoma, nor was it large enough or of sufficient duration to examine risk of invasive colorectal cancer. The results of other ongoing adenoma recurrence studies are awaited with interest (Table 1). It is important to note that the dose of calcium salt administered may be important; the usual daily doses in trials have ranged from 1,250 to 2,000 mg of calcium.

Postmenopausal Female Hormone Supplements

Several epidemiologic studies have suggested a decreased risk of colon cancer among users of postmenopausal female hormone supplements.[56-58] For rectal cancer, most studies have observed no association or a slightly elevated risk. [59-61]

Other Factors

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Several but not all epidemiological studies have reported a reduction in colon cancer incidence associated with the use of aspirin. Several cohort studies suggest a preventive effect of aspirin. Among a group of over 600,000 adults enrolled in an American Cancer Society study, mortality in regular users of aspirin was about 40% lower for cancers of the colon and rectum.[62,63] In a study of over 11,000 men and women in Sweden with rheumatoid arthritis (and presumably ingesting NSAIDs), colon cancer incidence was 37% lower and rectal cancer was 28% lower than predicted from cancer registry data.[64] In a report from the Health Professionals Follow-up Study of 47,000 males, regular use of aspirin (at least 2 times per week) was associated with a 30% overall reduction in colorectal cancer including a 50% reduction in advanced cases.[65] A population-based retrospective cohort study of nonaspirin NSAID use among individuals aged 65 and older was also associated with lower risk, particularly with increasing durations of use.[66] In the Physicians' Health Study, 22,000 men aged 40 to 84 were randomized to placebo or aspirin (325 mg every other day) for 5 years. There was no reduction in invasive cancers or adenomas at a median follow-up of 4.5 years.[67] In a subsequent analysis over a 12-year period, both randomized and observational analyses indicated that there was no association between the use of aspirin and the incidence of colorectal cancer. The low dose of aspirin and the short treatment period may account for the null findings.[68] Several studies, conducted in a rigorous manner, have demonstrated the effectiveness of sulindac in reducing the size and number of adenomas in familial polyposis.[69,70]

The NSAID piroxicam, at a dose of 20 mg/day, reduced mean rectal prostaglandin concentration by 50% in individuals with a history of adenomas.[71] Several studies are in progress assessing the effect of aspirin or other nonsteroidals on polyp recurrence following polypectomy.[28] In several of these studies, mucosal prostaglandin concentration is being measured.

The potential for the use of NSAIDs as a primary prevention measure is being studied. However, there are several unresolved issues that mitigate against making general recommendations for their use. These include a paucity of knowledge about the proper dose and duration for these agents, and concern about whether the potential preventive benefits would balance such long-term risks as gastrointestinal ulceration and hemorrhagic shock for the average risk individual.[72]

Physical Activity

A sedentary lifestyle has been associated in some [73,74] but not all [75] studies with an increased risk of colorectal cancer. There are numerous observational studies that have examined the relationship between physical activity and colon cancer risk. [76] Most of these studies have shown an inverse relationship between level of physical activity and colon cancer incidence. The average relative risk reduction is reportedly 40 to 50%. However, it is not known if or to what degree the observed association is due to confounding variables, such as diet or a genetic predisposition to colon cancer. In a population-based case control study of colorectal cancer among Chinese men and women in Western North America and China, colon and rectal cancer risk was elevated among men employed in sedentary occupations in both continents.[77] Further, the association between colorectal cancer risk and saturated fat was stronger among the sedentary than among the active population. Perhaps related to physical activity, body mass was found to be correlated with rectal cancer in men in an Australian study [75] and with colorectal cancer in men in Sweden.[78]

Alcohol Consumption

There is evidence of an association of colorectal cancer with alcoholic beverage consumption. In a meta-analysis, this association was weak.[79] In another review, statistically significant elevations of risk were found in males, particularly in regard to beer consumption and rectal cancer. It is hypothesized that alcohol may act to stimulate mucosal cell proliferation, to activate intestinal procarcinogens and possibly provide a source of unabsorbed carcinogens that can reach the distal large bowel.[80] Subsequently published case-control studies suggest a modest to strong positive relationship between alcohol consumption and large bowel cancers.[81,82]

Five studies have reported a positive association between alcohol intake and colorectal adenomas.[83] A case-control study of diet, genetic factors, and the adenoma-carcinoma sequence was conducted in Burgundy.[84] It separated adenomas less than 10 mm in diameter from larger adenomas. A positive association between current alcohol intake and adenomas was found to be limited to the larger adenomas suggesting that alcohol intake could act at the promotional phase of the adenoma-carcinoma sequence.[84]

Vitamins

In a prospective cohort study of 35,215 Iowa women, an inverse association between the risk of colon cancer and vitamin E intake was found; the relative risk for the highest compared to the lowest quartile was 0.3 (95% CI 0.19-0.54).[85] In a population-based case-control study, an inverse relationship between vitamin D intake and risk of colorectal cancer was found.[86] A prospective cohort study observed that higher energy-adjusted folate intake in the form of multivitamins containing folic acid was related to a lower risk for colon cancer (relative risk = 0.69, 95% CI 0.52-0.93) for intake greater than 400 ug/day compared with intake less than or equal to 200 ug/day after controlling for age, family history of colorectal cancer, aspirin use, smoking, body mass, physical activity, and intakes of red meat, alcohol, methionine, and fiber.[87]

Cigarette Smoking

Most case-control studies of cigarette exposure and adenomas have found an elevated risk for smokers.[21] In addition, a significantly increased risk of adenoma recurrence following polypectomy has been associated with smoking in both men and women.[21] In the Nurses' Health Study, the minimum induction period for cancer appears to be at least 35 years.[88] Similarly, in the Health Professionals Follow-up Study, a history of smoking was associated with both small and large adenomas and with a long induction period of at least 35 years for colorectal cancer.[89] In the Cancer Prevention Study II (CPS II), a large nationwide cohort study, multivariate-adjusted colorectal cancer mortality rates were highest among current smokers, intermediate among former smokers, and lowest in never smokers, with increased risk observed after 20 or more years of smoking in men and women combined.[90] Based on CPS II data, it was estimated that 12% of colorectal cancer deaths in the U.S. population in 1997 were attributable to smoking. A large population-based cohort study of Swedish twins found that heavy smoking of 35 or more years duration was associated with a nearly three-fold increased risk of developing colon cancer, although sub-site analysis found a statistically significant effect only for rectal but not colon cancer.[91] Another large population-based case-control study supports the view that current tobacco use and tobacco use within the last 10 years is associated with colon cancer. A 50% increase in risk was associated with smoking more than a pack a day relative to never smoking.[92] However, a 28-year follow-up of 57,000 Finns showed no association between the development of colorectal cancer and baseline smoking status, although there was a 57% to 71% increased risk in persistent smokers.[93] No relationship was found between cigarette smoking, even smoking of long duration, and recurrence of adenomas in a population followed for 4 years after initial colonoscopy.[94]

Polyp Removal

The National Polyp Study showed a greater than 75% reduction in the subsequent incidence of colorectal cancer after colonoscopic polypectomy compared with 3 nonconcurrent, external control groups.[95]

Fecal Occult Blood Testing

The Minnesota randomized trial of fecal occult blood tests investigated reduction in incidence of colorectal cancer. Nearly 85% of subjects with a positive test underwent diagnostic procedures that included colonoscopy or double contrast barium enema plus flexible sigmoidoscopy. After 18 years of follow-up, the incidence of colorectal cancer was reduced by 20% in the annually screened arm and 17% in the biennially screened arm.[96]

References:

  1. Rose DP, Boyar AP, Wynder EL: International comparisons of mortality rates for cancer of the breast, ovary, prostate, and colon, and per capita food consumption. Cancer 58(11): 2363-2371, 1986.
  2. Reddy BS: Dietary fat and its relationship to large bowel cancer. Cancer Research 41(9, Part 2): 3700-3705, 1981.
  3. Reddy BS, Narisawa T, Vukusich D, et al.: Effect of quality and quantity of dietary fat and dimethylhydrazine in colon carcinogenesis in rats. Proceedings of the Society for Experimental Biology and Medicine 151(2): 237-239, 1976.
  4. Nauss KM, Locniskar M, Newberne PM: Effect of alterations in the quality and quantity of dietary fat on 1,2-dimethylhydrazine-induced colon tumorigenesis in rats. Cancer Research 43(9): 4083-4090, 1983.
  5. Potter JD: Reconciling the epidemiology, physiology, and molecular biology of colon cancer. JAMA: Journal of the American Medical Association 268(12): 1573-1577, 1992.
  6. Potter JD, McMichael AJ: Diet and cancer of the colon and rectum: a case-control study. Journal of the National Cancer Institute 76(4): 557-569, 1986.
  7. Bingham SA: Diet and large bowel cancer. Journal of the Royal Society of Medicine 83(7): 420-422, 1990.
  8. Hirayama T, Tannenbaum SR, Reddy BS, et al.: A large-scale cohort study on the relationship between diet and selected cancers of the digestive organs. Banbury Report 7: 409-429, 1981.
  9. Bjelke E: Epidemiology of colorectal cancer, with emphasis on diet. International Congress Series 484: 158-174, 1980.
  10. Goldbohm RA, van den Brandt PA, van't Veer P, et al.: A prospective cohort study on the relation between meat consumption and the risk of colon cancer. Cancer Research 54(3): 718-723, 1994.
  11. Phillips RL, Snowdon DA: Dietary relationships with fatal colorectal cancer among Seventh-Day Adventists. Journal of the National Cancer Institute 74(2): 307-317, 1985.
  12. Willett WC, Stampfer MJ, Colditz GA, et al.: Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. New England Journal of Medicine 323(24): 1664-1672, 1990.
  13. Thun MJ, Calle EE, Namboodiri MM, et al.: Risk factors for fatal colon cancer in a large prospective study. Journal of the National Cancer Institute 84(19): 1491-1500, 1992.
  14. Bostick RM, Potter JD, Sellers TA, et al.: Relation of calcium, vitamin D, and dairy food intake to incidence of colon cancer among older women: the Iowa Women's Health Study. American Journal of Epidemiology 137(12): 1302-1317, 1993.
  15. Singh PN, Fraser GE: Dietary risk factors for colon cancer in a low-risk population. American Journal of Epidemiology 148(8): 761-774, 1998.
  16. Augustsson K, Skog K, Jagerstad M, et al.: Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population-based study. Lancet 353(9154): 703-707, 1999.
  17. Forman D: Meat and cancer: a relation in search of a mechanism. Lancet 353(9154): 686-687, 1999.
  18. Sugimura T: Carcinogenicity of mutagenic heterocyclic amines formed during the cooking process. Mutation Research 150(1-2): 33-41, 1985.
  19. Lee HP, Gourley L, Duffy SW, et al.: Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese. International Journal of Cancer 43(6): 1007-1016, 1989.
  20. Reddy BS, Hedges AR, Laakso K, et al.: Metabolic epidemiology of large bowel cancer: fecal bulk and constituents of high-risk North American and low-risk Finnish population. Cancer 42(6): 2832-2838, 1978.
  21. Neugut AI, Jacobson JS, DeVivo I: Epidemiology of colorectal adenomatous polyps. Cancer Epidemiology, Biomarkers and Prevention 2(2): 159-176, 1993.
  22. Kampman E, Giovannucci E, van't Veer P, et al.: Calcium, vitamin D, dairy foods, and the occurrence of colorectal adenomas among men and women in two prospective studies. American Journal of Epidemiology 139(1): 16-29, 1994.
  23. Neugut AI, Garbowski GC, Lee WC, et al.: Dietary risk factors for the incidence and recurrence of colorectal adenomatous polyps: a case-control study. Annals of Internal Medicine 118(2): 91-95, 1993.
  24. Schatzkin A, Lanza E, et al, and the Polyp Prevention Trial Study Group: Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. New England Journal of Medicine 342(16): 1149-1155, 2000.
  25. Cheah PY: Hypotheses for the etiology of colorectal cancer--an overview. Nutrition and Cancer 14(1): 5-13, 1990.
  26. Reddy BS, Engle A, Simi B, et al.: Effect of dietary fiber on colonic bacterial enzymes and bile acids in relation to colon cancer. Gastroenterology 102(5): 1475-1482, 1992.
  27. Morotomi M, Guillem JG, LoGerfo P, et al.: Production of diacylglycerol, an activator of protein kinase C, by human intestinal microflora. Cancer Research 50(12): 3595-3599, 1990.
  28. Vargas PA, Alberts DS: Colon cancer: the quest for prevention. Oncology (Huntington NY) 7(11 suppl): 33-40, 1993.
  29. Steinmetz KA, Potter JD: Vegetables, fruit, and cancer. I: epidemiology. Cancer Causes and Control 2(5): 325-357, 1991.
  30. Steinmetz KA, Potter JD: Vegetables, fruit, and cancer. II: mechanisms. Cancer Causes and Control 2(6): 427-442, 1991.
  31. Jacobs LR: Fiber and colon cancer. Gastroenterology Clinics of North America 17(4): 747-760, 1988.
  32. Roediger WE: The effect of bacterial metabolites on nutrition and function of the colonic mucosa: symbiosis between man and bacteria. In: Kasper H, Goebell H, eds.: Colon and Nutrition. Lancaster: Lancaster Press. Falk Symposium 32, 1981, pp 11-25.
  33. Jacobs LR: Relationship between dietary fiber and cancer: metabolic, physiologic, and cellular mechanisms. Proceedings of the Society for Experimental Biology and Medicine 183(3): 299-310, 1986.
  34. Howe GR, Bentino 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. Journal of the National Cancer Institute 84(24): 1887-1896, 1992.
  35. Potter JD: Epidemiology of diet and cancer: evidence of human maladaptation. In: Micozzi MS, Moon TE, eds.: Macronutrients: Investigating their Role of in Cancer. New York: Marcel Dekker, 1992, pp 55-84.
  36. Kritchevsky D: Dietary guidelines: the rationale for intervention. Cancer 72(Suppl 3): 1011-1014, 1993.
  37. Reddy B, Engle A, Katsifis S, et al.: Biochemical epidemiology of colon cancer: effect of types of dietary fiber on fecal mutagens, acid, and neutral sterols in healthy subjects. Cancer Research 49(16): 4629-4635, 1989.
  38. Fuchs CS, Giovannucci EL, Colditz GA, et al.: Dietary fiber and the risk of colorectal cancer and adenoma in women. New England Journal of Medicine 340(3): 169-176, 1999.
  39. World Cancer Research Fund in association with American Institute for Cancer Research: Food, Nutrition and the Prevention of Cancer: a Global Perspective. Washington, DC: American Institute for Cancer Research, 1997.
  40. Michels KB, Giovannucci E, Joshipura KJ, et al.: Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers. Journal of the National Cancer Institute 92(21): 1740-1752, 2000.
  41. Terry P, Giovannucci E, Michels KB, et al.: Fruit, vegetables, dietary fiber, and risk of colorectal cancer. Journal of the National Cancer Institute 93(7): 525-533, 2001.
  42. Alberts DS, Martinez ME, et al, and the Phoenix Colon Cancer Prevention Physicians' Network: Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. New England Journal of Medicine 342(16): 1156-1162, 2000.
  43. Wargovich MJ, Eng VW, Newmark HL, et al.: Calcium ameliorates the toxic effect of deoxycholic acid on colonic epithelium. Carcinogenesis 4(9): 1205-1207, 1983.
  44. Slattery ML, Sorenson AW, Ford MH: Dietary calcium intake as a mitigating factor in colon cancer. American Journal of Epidemiology 128(3): 504-514, 1988.
  45. Kune S, Kune GA, Watson LF: Case-control study of dietary etiological factors: the Melbourne Colorectal Cancer Study. Nutrition and Cancer 9(1): 21-42, 1987.
  46. Yang CY, Chiu HF: Calcium and magnesium in drinking water and risk of death from rectal cancer. International Journal of Cancer 77(4): 528-532, 1998.
  47. Zheng W, Anderson KE, Kushi LH, et al.: A prospective cohort study of intake of calcium, vitamin D, and other micronutrients in relation to incidence of rectal cancer among postmenopausal women. Cancer Epidemiology, Biomarkers and Prevention 7(3): 221-225, 1998.
  48. Manousos O, Day NE, Trichopoulos D, et al.: Diet and colorectal cancer: a case control study in Greece. International Journal of Cancer 32(1): 1-5, 1983.
  49. Wargovich MJ, Baer AR: Basic and clinical investigations of dietary calcium in the prevention of colorectal cancer. Preventive Medicine 18(5): 672-679, 1989.
  50. Lipkin M, Newmark H: Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. New England Journal of Medicine 313(22): 1381-1384, 1985.
  51. Buset M, Lipkin M, Winawer S, et al.: Inhibition of human colonic epithelial cell proliferation in vivo and in vitro by calcium. Cancer Research 46(10): 5426-5430, 1986.
  52. Wargovich MJ, Isbell G, Shabot M, et al.: Calcium supplementation decreases rectal epithelial cell proliferation in subjects with sporadic adenoma. Gastroenterology 103(1): 92-97, 1993.
  53. Bostick RM, Potter JD, Fosdick L, et al.: Calcium and colorectal epithelial cell proliferation: a preliminary randomized, double-blinded, placebo-controlled clinical trial. Journal of the National Cancer Institute 85(2): 132-141, 1993.
  54. Konishi H, Steinbach G, Hittelman WN, et al.: Cell kinetic analysis of intact rat colonic crypts by confocal microscopy and immunofluorescence. Gastroenterology 111(6): 1493-1500, 1996.
  55. Baron JA, Beach M, et al, for the Calcium Polyp Prevention Study Group: Calcium supplements for the prevention of colorectal adenomas. New England Journal of Medicine 340(2): 101-107, 1999.
  56. Calle EE, Miracle-McMahill HL, Thun MJ, et al.: Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausal women. Journal of the National Cancer Institute 87(7): 517-523, 1995.
  57. Newcomb PA, Storer BE: Postmenopausal hormone use and risk of large-bowel cancer. Journal of the National Cancer Institute 87(14): 1067-1071, 1995.
  58. Grodstein F, Newcomb PA, Stampfer MJ: Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis 106(5): 574-582, 1999.
  59. Risch HA, Howe GR: menopausal hormone use and colorectal cancer in Saskatchewan: a record linkage cohort study. Cancer Epidemiology, Biomarkers and Prevention 4(1): 21-28, 1995.
  60. Gerhardsson de Verdier M, London S: Reproductive factors, exogenous female hormones, and colorectal cancer by subsite. Cancer Causes and Control 3(4): 355-360, 1992.
  61. Prihartono N, Palmer JR, Louik C, et al.: A case-control study of use of postmenopausal female hormone supplements in relation to the risk of large bowel cancer. Cancer Epidemiology, Biomarkers and Prevention 9(4): 443-447, 2000.
  62. Thun MJ, Namboodiri MM, Health CW: Aspirin use and reduced risk of fatal colon cancer. New England Journal of Medicine 325(23): 1593-1596, 1991.
  63. Thun MJ, Namboodiri MM, Calle EE, et al.: Aspirin use and risk of fatal cancer. Cancer Research 53(6): 1322-1327, 1993.
  64. Gridley G, McLaughlin JK, Ekbom A, et al.: Incidence of cancer among patients with rheumatoid arthritis. Journal of the National Cancer Institute 85(4): 307-311, 1993.
  65. Giovannucci E, Rimm EB, Stampfer MJ, et al.: Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Annals of Internal Medicine 121(4): 241-246, 1994.
  66. Smalley W, Ray WA, Daugherty J, et al.: Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study. Archives of Internal Medicine 159(2): 161-166, 1999.
  67. Gann PH, Manson JE, Glynn RJ, et al.: Low-dose aspirin and incidence of colorectal tumors in a randomized trial. Journal of the National Cancer Institute 85(15): 1220-1224, 1993.
  68. Sturmer T, Glynn RJ, Lee IM, et al.: Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians' Health Study. Annals of Internal Medicine 128(9): 713-720, 1998.
  69. Labayle D, Fischer D, Vielh P, et al.: Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology 101(3): 635-639, 1991.
  70. Giardiello FM, Hamilton SR, Krush AJ, et al.: Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. New England Journal of Medicine 328(18): 1313-1316, 1993.
  71. Earnest DL, Hixson LJ, Fennerty MB, et al.: Inhibition of prostaglandin synthesis: potential for chemoprevention of human colon cancer. Cancer Bulletin 43(6): 561-568, 1991.
  72. Sandler RS: Aspirin and other nonsteroidal anti-inflammatory agents in the prevention of colorectal cancer. Cancer: Principles and Practice of Oncology Updates 11(6): 1-14, 1997.
  73. White E, Jacobs EJ, Daling JR: Physical activity in relation to colon cancer in middle-aged men and women. American Journal of Epidemiology 144(1): 42-50, 1996.
  74. Slattery ML, Schumacher MC, Smith KR, et al.: Physical activity, diet, and risk of colon cancer in Utah. American Journal of Epidemiology 128(5): 989-999, 1988.
  75. Kune GA, Kune S, Watson LF: Body weight and physical activity as predictors of colorectal cancer risk. Nutrition and Cancer 13(1-2): 9-17, 1990.
  76. Friedenreich CM: Physical activity and cancer prevention: from observational to intervention research. Cancer Epidemiology, Biomarkers and Prevention 10(4): 287-301, 2001.
  77. Whittemore AS, Wu-Williams AH, Lee M, et al.: Diet, physical activity, and colorectal cancer among Chinese in North America and China. Journal of the National Cancer Institute 882(11): 915-926, 1990.
  78. Gerhardsson de Verdier M, Hagman U, Steineck G, et al.: Diet, body mass and colorectal cancer: a case-referent study in Stockholm. International Journal of Cancer 46(5): 832-838, 1990.
  79. Longnecker MP, Orza MJ, Adams ME, et al.: A meta-analysis of alcoholic beverage consumption in relation to risk of colorectal cancer. Cancer Causes and Control 1(1): 59-68, 1990.
  80. Kune GA, Vitetta L: Alcohol consumption and the etiology of colorectal cancer: a review of the scientific evidence from 1957 to 1991. Nutrition and Cancer 18(2): 97-111, 1992.
  81. Newcomb PA, Storer BE, Marcus PM: Cancer of the large bowel in women in relation to alcohol consumption: a case-control study in Wisconsin (United States). Cancer Causes and Control 4(5): 405-411, 1993.
  82. Meyer F, White E: Alcohol and nutrients in relation to colon cancer in middle-aged adults. American Journal of Epidemiology 138(4): 225-236, 1993.
  83. Boutron MC, Faivre J: Diet and the adenoma-carcinoma sequence. European Journal of Cancer Prevention 2(Suppl 2): 95-98, 1993.
  84. Boutron MC, Faivre J: Alcohol, tobacco and the adenoma-carcinoma sequence: a case-control study in Burgundy, France. Gastroenterology 104(4 suppl): A-390, 1993.
  85. Bostick RM, Potter JD, McKenzie DR, et al.: Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women's Health Study. Cancer Research 53(18): 4230-4237, 1993.
  86. Pritchard RS, Baron JA, De Verdier MG: Dietary calcium, vitamin D, and the risk of colorectal cancer in Stockholm, Sweden. Cancer Epidemiology, Biomarkers and Prevention 5: 897-900, 1996.
  87. Giovannucci E, Stampfer MJ, Colditz GA, et al.: Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Annals of Internal Medicine 129(7): 517-524, 1998.
  88. 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. Journal of the National Cancer Institute 86(3): 192-199, 1994.
  89. Giovannucci E, Rimm EB, Stampfer MJ, et al.: A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in U.S. men. Journal of the National Cancer Institute 86(3): 183-191, 1994.
  90. Chao A, Thun MJ, Jacobs EJ et al.: Cigarette smoking and colorectal cancer mortality in the Cancer Prevention study II 92(23): 1888-1896, 2000.
  91. Terry P, Ekbom A, Lichtenstein P, et al.: Long-term tobacco smoking and colorectal cancer in a prospective cohort study 91: 585-587, 2001.
  92. Slattery ML, Potter JD, Friedman GD, et al.: Tobacco use and colon cancer. International Journal of Cancer 70(3): 259-264, 1997.
  93. Knekt P, Hakama M, Jarvinen R, et al.: Smoking and risk of colorectal cancer. British Journal of Cancer 78(1): 136-139, 1998.
  94. Baron JA, Sandler RS, Haile RW, et al.: Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas. Journal of the National Cancer Institute 90(1): 57-62, 1998.
  95. Winawer SJ, Zauber AG, Ho MN, et al. for the National Polyp Study Workgroup: Prevention of colorectal cancer by colonoscopic polypectomy. New England Journal of Medicine 329(27): 1977-1981, 1993.
  96. Mandel JS, Church TR, Bond JH, et al.: The effect of fecal occult-blood screening on the incidence of colorectal cancer. New England Journal of Medicine 343(22): 1603-1607, 2000.
Date Last Modified: 07/2002

This information from PDQ is reviewed regularly by members of the PDQ Editorial Boards. If you have specific comments on the content of this information, direct them to: PDQ Editorial Board, CIPS/NCI, 6116 Executive Boulevard, Suite 3002B, MSC-8321, 20892-8321, fax: 301-480-8105. * * The PDQ database also contains listings of clinical trial protocols and directories of organizations and physicians who treat cancer patients, but this information is not available through CancerMail. For more information on accessing PDQ, consult the CancerMail Contents List.

MEDEVENT Congress Server Browse and Submit Oncology Conferences

Sponsors:

  <A HREF ="deutsch/CancernetDSL.ram">Play clip using the stand-alone RealPlayer!</A><A HREF ="http://www.real.com/products/player/d1.html">Click here to download the latest RealPlayer!</A>
small video clip about our work (200 Kbit/s)


Back to the Cancernet contents overview
Questions? Mail them to us!		 We subscribe to the HON-Code principles of the Health On the Net Foundation We subscribe to the HONcode principles
of the Health On the Net Foundation


Dr. G. Quade
This page was last modified on Sunday, 02-Nov-2003 15:58:08 CET
Impressum