Colon cancer and fiber

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Hi All,

Fiber may not significantly reduce colon cancer risk, it seems, based on the

pdf-available papers story below.

This Week in JAMA

JAMA. 2005;294:2811.

Dietary Fiber and Risk of Colorectal Cancer

The contribution of dietary fiber intake to colorectal cancer risk, assessed in

many

studies since the late 1960s, is not clear. In an analysis by Park and

colleagues,

(SEE ARTICLE) which pooled data from 13 prospective cohort studies of dietary

fiber

and incident colorectal cancer, the authors found a significant inverse

relationship

between dietary fiber intake and colorectal cancer risk in analyses adjusted for

age.However, this association was attenuated and no longer significant when

other

colorectal cancer risk factors were taken into account. In an editorial, Baron

(SEE

ARTICLE) discusses how the nature of dietary fiber, lifestyle factors related to

fiber consumption, and measurement error complicate analyses of a

fiber–colorectal

cancer connection.

Editorials

Dietary Fiber and Colorectal Cancer: An Ongoing Saga

A. Baron

JAMA. 2005;294:2904-2906.

Dietary fiber has had a long and complicated relationship with colorectal

cancer.

The idea that intake of fiber might protect against this malignancy dates back

at

least to the late 1960s, when Burkitt1 proposed that the low rates of colorectal

cancer he observed in southern Africa (as well as the low rates of appendicitis,

diverticular disease, and colorectal adenomas) were related to high-fiber

intake.

Subsequently, hemorrhoids, constipation, hypertension, hyperlipidemia,

cardiovascular disease, and diabetes have been added to the list of problems

that

may be prevented by dietary fiber intake.

Of these disorders and diseases, colorectal cancer arguably has the most

confusing

association with fiber. Animal studies have variably suggested that fiber has

reduced risks, increased risks, or had no effect on experimental bowel cancer.2

Epidemiological studies have found intake of dietary fiber to be either

protective,

to have no effect,3-6 or even rarely to confer an increase in risk.7

Intervention

trials (with adenoma end points) have found either no effect or increased

risks.8-12

It is certainly reasonable to ask the question: why has this been so difficult?

Part of the problem is dietary fiber itself. The term came into use in the

1970s,

but the precise definition continues to evolve.13-15 Although the term fiber

suggests a single entity, fiber actually represents a group of plant products

that

may have very different properties.2, 13-15 Measuring dietary fiber intake is as

uninformative as knowing that a patient with pneumonia took " some antibiotic or

other. " Clearly dietary " fibers " would be a better way to refer to these

substances,

and it would be best to consider fibers in biologically meaningful groups, even

if

it is not practical to think of them individually. To add to the confusion, the

biological effects of specific fibers may vary depending on whether a fiber is

studied in isolation or in combination with other cell wall constituents.15

Furthermore, there is a need for improvements in the measurement of the various

fibers.14

In epidemiological studies, fibers are often categorized by the foods that

contain

them (eg, cereal fiber, fruit fiber, vegetable fiber). This is a convenient

method

of categorization, but these groupings retain substantial heterogeneity. A more

physiologically helpful breakdown would be grouping fibers into categories of

soluble and insoluble.3 Insoluble fibers have the stool-bulking effect that is

often

associated in the public mind with fiber, but soluble fibers typically do not

have

this effect2 because they are readily broken down in the large bowel. Fruit and

vegetable fiber is largely soluble, but cereal fiber may be either soluble (eg,

oat

bran) or insoluble (wheat bran).

Dietary fibers often do not conform to their popular image. Despite the name,

most

are not fibrous, are certainly not just roughage. Most are polysaccharides.

Although

one feature dietary fibers share is a resistance to breakdown by alimentary

enzymes,13 much dietary fiber, in fact, is digested by bacteria in the colon.

The heterogeneity of dietary fibers has been a major contributor to the

confusion

regarding associations with colorectal cancer. In animal models, insoluble

fibers

such as wheat fiber have typically resulted in inhibition of bowel

carcinogenesis,

but soluble fibers such as pectins have tended to increase the numbers of

tumors.2

In human epidemiological studies that have found an inverse association with

risk,

the opposite pattern has been observed—fruit and vegetable (largely soluble)

fibers

more often have been found to be protective, while cereal fibers have not.3 On

the

other hand, ecological studies (that use data on groups rather than individuals)

have tended to find cereal fibers protective.3 In general, prospective studies

have

shown no association. Clinical trials of wheat bran (with an adenoma end point)

have

been uniformly negative8-9,11-12; one trial that used a soluble fiber (psyllium)

reported increased adenoma risks.10 Thus, the relationship between intake of

dietary

fibers and colorectal cancer risk has depended on the type of fiber under

discussion

and the research design used. These discrepant findings do not permit a clear

picture of how dietary fiber, or even some fiber groups, affect cancer of the

large

bowel.

In addition to the physiological complexity of the different fibers,

epidemiological

studies confront several challenges. One problem is that whatever dietary fiber

is,

it seems to be a highly confounded lifestyle factor. That is, fiber intake is

related to consumption of other nutrients and to personal characteristics and

traits

that are associated with risk of colorectal cancer. This mixing of exposures can

lead to distortion of the observed fiber-cancer association. Of course

statistical

adjustments can be made if these other factors are measured, but sometimes they

can

not be assessed or (worse) have not been identified. As a result, in

epidemiological

studies the relative risks for fiber intake seem to vary in important ways,

depending on what variables are controlled.5-6,16 Epidemiological studies of

associations with intake of dietary fibers are also hampered by the measurement

error that is inherent in dietary assessment.17 These errors form a statistical

uncertainty that generally tends to obscure associations. This problem can be

quite

severe, hiding even moderately strong associations.

One major advantage of a combined analysis such as that reported by Park and

colleagues16 in this issue of JAMA is that the large number of participants

included

in the analysis will enable investigators to detect relatively modest

associations

and to assess effects in subgroups—for example, individuals with very high or

very

low fiber intake. However, the large sample size will not help with confounding,

nor

will it overcome measurement error.

In their combined analysis of 13 prospective studies, Park et al16 found

evidence of

an increased risk of colorectal cancer among individuals with very low intake of

total dietary fiber (about the lowest 11%). After adjustment for measurement

error,

the relative risk for intakes of less than 10 g per day vs 10 or more g per day

increased from 1.22 to 2.16. These findings suggest that colorectal cancer might

be

a sort of " fiber deficiency disease, " such that a relatively modest minimum

intake

prevents an increased risk. For colorectal cancer overall, the authors did not

detect any further reduction in risk at higher intakes. Nonetheless, for rectal

cancer there were suggestions that fiber intake at the high end of the scale

conferred a modest decrease in risk (about 15%) compared with moderate intake.

The

contrast between the highest and lowest quintiles of fiber intake (a more

commonly

used comparison) was even greater, although not detailed explicitly. It would be

particularly interesting to see this estimate corrected for measurement error,

as

the authors did for the association between overall colorectal cancer risk and

low

fiber intake. If the rectal cancer analysis was as strongly affected by

measurement

error as that one, the result could be a substantial gradient from lowest to

highest

intake. If so, exploration of the types of fiber involved would be important.

The combined analysis by Park et al16 yields an " average " effect size across the

studies that contributed data. But of course it cannot reflect studies that are

not

included, such as the recently published EPIC cohort analysis.4 This study is a

combined analysis of separate cohorts which together had about 50% more cases

than

the largest of the studies in the analysis by Park et al.16 In an

error-corrected

analysis, the EPIC investigators found a more than 40% reduction in risk of

colorectal cancer for individuals in the highest quintile of dietary fiber

intake vs

the lowest, a much greater difference than the (uncorrected) results reported by

Park et al.16

The findings by Park et al16 and the results of the EPIC4 analysis provide at

least

some indications that dietary fiber of some sort is related in some way to colon

or

rectal cancer risk. However, the 2 studies have not addressed exactly the same

issues and, therefore, the extent of agreement or disagreement is not

well-defined.

Over the short term, wheat fiber or psyllium interventions do not seem to affect

colorectal carcinogenesis, but understanding longer-term relationships with any

type

of fiber will require more work. Studies like that of Park et al16 provide

valuable

help, but unfortunately there is more to do.

Dietary Fiber Intake and Risk of Colorectal Cancer: A Pooled Analysis of

Prospective

Cohort Studies

Yikyung Park; J. Hunter; Donna Spiegelman; Leif Bergkvist; Franco Berrino;

Piet A. van den Brandt; E. Buring; Graham A. Colditz; Jo L. Freudenheim;

S. Fuchs; Giovannucci; R. andra Goldbohm; Saxon Graham;

Harnack; Anne M. Hartman; R. s Jr; Ikuko Kato; Vittorio Krogh;

F.

Leitzmann; Marjorie L. McCullough; B. ; Pirjo Pietinen; E.

Rohan; Arthur Schatzkin; Walter C. Willett; Alicja Wolk; Anne

Zeleniuch-Jacquotte;

Shumin M. Zhang; A. -Warner

JAMA. 2005;294:2849-2857.

ABSTRACT

Context Inconsistent findings from observational studies have continued the

controversy over the effects of dietary fiber on colorectal cancer.

Objective To evaluate the association between dietary fiber intake and risk of

colorectal cancer.

Design, Setting, and Participants From 13 prospective cohort studies included

in

the Pooling Project of Prospective Studies of Diet and Cancer, 725 628 men and

women

were followed up for 6 to 20 years across studies. Study- and sex-specific

relative

risks (RRs) were estimated with the proportional hazards model and were

subsequently pooled using a random-effects model.

Main Outcome Measure Incident colorectal cancer.

Results During 6 to 20 years of follow-up across studies, 8081 colorectal

cancer

cases were identified. For comparison of the highest vs lowest study- and

sex-specific quintile of dietary fiber intake, a significant inverse association

was

found in the age-adjusted model (pooled RR = 0.84; 95% confidence interval [CI],

0.77-0.92). However, the association was attenuated and no longer statistically

significant after adjusting for other risk factors (pooled multivariate RR =

0.94;

95% CI, 0.86-1.03). In categorical analyses compared with dietary fiber intake

of 10

to <15 g/d, the pooled multivariate RR was 1.18 (95% CI, 1.05-1.31) for less

than 10

g/d (11% of the overall study population); and RR, 1.00 (95% CI, 0.85-1.17) for

30

or more g/d. Fiber intake from cereals, fruits, and vegetables was not

associated

with risk of colorectal cancer. The pooled multivariate RRs comparing the

highest vs

lowest study- and sex-specific quintile of dietary fiber intake were 1.00 (95%

CI,

0.90-1.11) for colon cancer and 0.85 (95% CI, 0.72-1.01) for rectal cancer (P

for

common effects by tumor site = .07).

Conclusions In this large pooled analysis, dietary fiber intake was inversely

associated with risk of colorectal cancer in age-adjusted analyses. However,

after

accounting for other dietary risk factors, high dietary fiber intake was not

associated with a reduced risk of colorectal cancer.

Al Pater, PhD; email: old542000@...

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