Lieberman DA, Prindiville S, Weiss DG, Willett W, for the VA Cooperative Study Group 380 . Risk Factors for Advanced Colonic Neoplasia and Hyperplastic Polyps in Asymptomatic Individuals. JAMA. 2003;290(22):2959–2967. doi:10.1001/jama.290.22.2959
Author Affiliations: Department of Veterans Affairs Medical Center, Portland, Ore (Dr Lieberman); National Cancer Institute, Bethesda, Md (Dr Prindiville); Department of Veterans Affairs Medical Center, Perry Point, Md (Dr Weiss); and Harvard School of Public Health, Boston, Mass (Dr Willett).
Context Knowledge of risk factors for colorectal neoplasia could inform risk
reduction strategies for asymptomatic individuals. Few studies have evaluated
risk factors for advanced colorectal neoplasia in asymptomatic individuals,
compared risk factors between persons with and without polyps, or included
most purported risk factors in a multivariate analysis.
Objective To determine risk factors associated with advanced colorectal neoplasia
in a cohort of asymptomatic persons with complete colonoscopy.
Design, Setting, and Participants Prospective, cross-sectional study of 3121 asymptomatic patients aged
50 to 75 years from 13 Veterans Affairs medical centers conducted between
February 1994 and January 1997. All participants had complete colonoscopy
to determine the prevalence of advanced neoplasia, defined as an adenoma that
was 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade
dysplasia, or invasive cancer. Variables examined included history of first-degree
relative with colorectal cancer, prior cholecystectomy, serum cholesterol
level, physical activity, smoking, alcohol use, and dietary factors.
Main Outcome Measures An age-adjusted analysis was performed for each variable to calculate
the odds ratios (ORs) and 95% confidence intervals (CIs) associated with having
advanced neoplasia compared with having no polyps. We developed a multivariate
logistic regression model to identify the most informative risk factors. A
secondary analysis examined risk factors for having hyperplastic polyps compared
with having no polyps and compared with having advanced neoplasia.
Results Three hundred twenty-nine participants had advanced neoplasia and 1441
had no polyps. In multivariate analyses, we found positive associations for
history of a first-degree relative with colorectal cancer (OR, 1.66; 95% CI,
1.16-2.35), current smoking (OR, 1.85; 95% CI, 1.33-2.58), and current moderate
to heavy alcohol use (OR, 1.02; 95% CI, 1.01-1.03). Inverse associations were
found for cereal fiber intake (OR, 0.95; 95% CI, 0.91-0.99), vitamin D intake
(OR, 0.94; 95% CI, 0.90-0.99), and use of nonsteroidal anti-inflammatory drugs
(NSAIDs) (OR, 0.66; 95% CI, 0.48-0.91). In the univariate analysis, the inverse
association was found with cereal fiber intake greater than 4.2 g/d, vitamin
D intake greater than 645 IU/d, and daily use of NSAIDs. Marginal factors
included physical activity, daily multivitamin use, and intake of calcium
and fat derived from red meat. No association was found for body mass index,
prior cholecystectomy, or serum cholesterol level. Three hundred ninety-one
patients had hyperplastic polyps as the worst lesion found at colonoscopy.
Risk variables were similar to those for patients with no polyps, except that
past and current smoking were associated with an increased risk of hyperplastic
Conclusions Our data endorse several important risk factors for advanced colonic
neoplasia and provide a rationale for prudent risk reduction strategies. Further
study is needed to determine if lifestyle changes can moderate the risk of
Colorectal cancer is the second leading cause of cancer death in North
America. Evidence exists that screening asymptomatic populations beginning
at age 50 years can reduce mortality due to colorectal cancer1- 8 and
that removal of precursor adenomas may reduce the incidence of colorectal
cancer.9,10 Identification of
important risk factors for advanced colonic neoplasia could inform both risk
stratification and development of risk reduction strategies.
Many potential risk factors for colorectal neoplasia have been investigated
previously.11,12 Few studies have
evaluated risk factors for advanced colorectal neoplasia in asymptomatic individuals,
compared risk factors between persons with and without polyps, or included
most purported risk factors in a multivariate analysis. We conducted a cross-sectional
study to determine risk factors for advanced colonic neoplasia in asymptomatic
persons undergoing a complete screening colonoscopic examination. The unique
features of this study are (1) the inclusion of persons known to be free of
colonic polyps based on colonoscopy as a comparison group vs patients with
advanced neoplasia and (2) a sample size sufficient to analyze the most important
risk variables in a multivariate analysis. Suspected risk factors were selected
based on associations found in prior studies and biological plausibility.
We studied family history of colorectal cancer, diet, smoking, alcohol use,
nonsteroidal anti-inflammatory drug (NSAID) use, body mass index, prior cholecystectomy,
serum cholesterol level, and physical activity as potential risk factors.
We performed a secondary analysis of patients whose worst colonic lesions
were 1 or more hyperplastic polyps. Hyperplastic polyps are benign and common.13,14 Current guidelines suggest that patients
with hyperplastic polyps be treated similarly to patients with no polyps.15 No prior studies have evaluated risk factors in patients
with hyperplastic polyps to determine if they resemble those in patients with
no polyps. Our study provided an opportunity to determine risk variables for
patients with hyperplastic polyps compared with those in patients with no
polyps and with those in patients with advanced neoplasia.
Patients aged 50 to 75 years who did not have lower gastrointestinal
tract symptoms were recruited from 13 Veterans Affairs medical centers between
February 1994 and January 1997.16 The study
protocol was approved by a central human rights committee and by institutional
review boards at each participating center, and all participants provided
written informed consent. Patients completed a clinic survey to determine
eligibility. Patients were excluded if they reported symptoms of lower gastrointestinal
tract disease, including rectal bleeding (on ≥1 occasion in the previous
6 months), a marked change in bowel habits, or lower abdominal pain that would
normally require medical evaluation. Other exclusion criteria were current
participation in other studies, history of disease of the colon (such as colitis,
polyps, or cancer), prior colonic surgery, a colonic examination (ie, sigmoidoscopy,
colonoscopy, or barium enema) within the previous 10 years, a medical condition
that could increase the risk associated with colonoscopy or that would preclude
a benefit from colonoscopic screening (cancer or any terminal illness), a
prosthetic heart valve, anticoagulant therapy, nonmedical problems (psychiatric
disorders, lack of transportation, homelessness or lack of support at home,
or excessive use of alcohol), or a need for special precautions in performing
colonoscopy (such as antibiotic prophylaxis). Women with childbearing potential
were excluded. A total of 17 732 patients were screened for enrollment;
2346 patients declined to complete the clinic survey. The most common reasons
for exclusion were colonic examination in the previous 10 years (n = 6486),
history of colon disease (n = 2221), serious medical disorder (n = 1052),
and anticoagulation therapy (n = 712). Among patients who met the eligibility
criteria, 1463 (31.4%) declined to participate and 3196 eligible patients
were enrolled. Patients who had complete colonoscopy examinations were included
in this analysis (n = 3121). We determined our sample size requirements to
have sufficient power (>90%) to detect a clinically important doubling of
risk for key categorical risk factors. We analyzed the 329 patients with advanced
neoplasia and 1441 without polyps (N = 1770) (Table 1).
Procedures for performing colonoscopy and histologic evaluation have
been described previously.16 Advanced colonic
neoplasia was defined as an adenoma of 10 mm or more, a villous adenoma (at
least 25% villous), adenoma with high-grade dysplasia, or invasive cancer.
Patients with a pathologic interpretation of intramucosal carcinoma or carcinoma
in situ were classified in the high-grade dysplasia group. Cancer was defined
as invasion of malignant cells beyond the muscularis mucosa. Patients were
classified based on the most histologically advanced lesion. A second cohort
of patients in whom hyperplastic polyps were the worst colonic lesions was
studied to determine if their risk factors differed from those of patients
with no polyps or from those of patients with advanced neoplasia.
Diet. Diet was assessed with a semiquantitative
food frequency questionnaire that has been validated in prior studies.17,18 Patients were excluded if they left
70 or more items blank or reported implausibly high or low scores for total
energy intake. Based on this questionnaire, the following measurements were
made in each patient: total energy intake; total fat; fat derived from beef,
pork, or lamb; total dietary fiber; fiber from cereal, fruits, and vegetables;
total calcium; total folate; vitamin D; and daily multivitamin use.
Physical Activity. Two methods were used to
assess the impact of regular daily physical activity and the role of sporadic
but vigorous exercise. The physical activity index was adopted from the Framingham
Study.19 Patients were provided definitions
of very light, light, moderate, and heavy activity for home, occupation, and
recreation and recorded their time spent in each category to generate a 24-hour
score. The second measure used a calculation of metabolic equivalents, a well-validated
assessment of energy expenditure during specific forms of moderate to heavy
exercise, expressed as metabolic equivalents per week.20,21 The
2 scoring systems reflect different profiles of physical activity. On the
physical activity index, an individual who engages in many hours per day of
mild activity may have a similar score to a person who performs a short period
of exertional activity. In contrast, the metabolic equivalent score discriminates
individuals who engage in moderate to heavy physical activity; an individual
with several hours of mild activity will have a lower score than a person
with short periods of heavy exertion.
Alcohol, Smoking, and NSAIDs. Past and current
smoking habits were ascertained. Patients were queried regarding current use,
number of cigarettes per day, and number of years of smoking. For prior smokers,
the year of cessation, number of years of smoking, and number of cigarettes
per day were determined. The number of pack-years was calculated for both
groups. Current and past use of alcohol was measured by ascertaining the number
of drinks per week, defined as wine (4 oz per glass), beer (12 oz per can
or bottle), or liquor (1 oz per shot), each equivalent to approximately 11
g of alcohol per drink.
Use of aspirin or other NSAIDs was ascertained by a query that included
every known NSAID. This list was revised and updated during the study as new
products became available. Patients indicated specific product used, daily
dosage, and duration (in years) of consumption. The data were analyzed based
on current use (never vs occasional or daily) and on duration of any use.
Other Factors. Body mass index was calculated
as weight in kilograms divided by the square of height in meters. History
of prior cholecystectomy and date of surgery were ascertained. Serum cholesterol
was measured from a fasting blood sample.
Study database management and all statistical analyses were performed
with SAS software, version 6.12 (SAS Institute Inc, Cary, NC). Descriptive
statistical analyses included calculation of rates and proportions for categorical
data and means and SEs for continuous data. In addition, standard logistic
regression methods were used for calculating relative risks as odds ratios
(ORs) with 95% confidence intervals (CIs).22 In
the analysis of dietary and other continuous variables, participants were
categorized according to quintiles ranging from lowest to highest values,
with the lowest quintile serving as the reference group. Dietary variables
were adjusted first for age and then for age plus total energy intake and
medical history factors (family history, body mass index, smoking, alcohol
use, physical activity index, and NSAID use). Nondietary risk factors were
adjusted for age.
A primary objective was to assess in a multivariate model the relative
importance of the risk factors. These factors fell into general classes within
which there were multiple measures (eg, physical activity; dietary fiber as
total and cereal, fruit, and vegetable). The development of the multivariate
model required variable selection to avoid problems of redundancy and overspecification.
In cases of ambiguity, a statistical approach involving stepwise regression
procedures was used within classes of factors to select the most statistically
relevant variables. The multivariate model included the following list of
variables, rescaled with reasonable increments: family history (≥1 first-degree
relatives with colorectal cancer vs none); body mass index (continuous in
5-unit increments); physical activity index (continuous in 5-unit increments);
smoking (current vs never or past); alcohol use (continuous by number of servings
per week); NSAID use (any vs never); beef, pork, or lamb as main dish (continuous
as a percentage of total energy intake) representing the fat class of dietary
factors; cereal fiber (continuous in 1-g increments) as the fiber variable;
and vitamin D (continuous in 100-IU increments). For all analyses, P<.05 was considered statistically significant.
A total of 3121 persons had complete colonoscopy to the cecum and have
been previously described.16 Men accounted
for 96.8% of this cohort, so these results cannot be generalized to women.
Patients were classified by the worst histologic lesion found in the colon.
A total of 1441 patients had no polyps, 118 (3.8%) had nonadenomatous lesions,
391 (12.5%) had hyperplastic polyps, and 842 (27.0%) had 1 or more tubular
adenomas less than 1 cm in diameter. Three hundred twenty-nine patients (10.5%)
had at least 1 advanced neoplastic lesion in the colon and are the subject
of this analysis. These patients were compared with 1441 patients who had
no polyps or growths in the colon. Complete medical history information was
obtained for all patients. Complete dietary information was obtained for 312
patients with advanced neoplasia (94.8%) and for 1359 patients with no neoplasia
(94.3%). Patients with advanced neoplasia were older than patients with no
neoplasia (65.1 years vs 62.7 years; P<.001).
All ORs are adjusted for age.
The results of the age-adjusted analysis of medical history risk factors
are summarized in Table 1. Patients
with at least 1 first-degree relative with colorectal cancer had an increased
risk of advanced neoplasia (OR, 1.68; 95% CI, 1.21-2.31), which was higher
if patients had 2 first-degree relatives with colorectal cancer. Sixteen (28%)
of 57 participants with young index relatives (<60 years) had advanced
neoplasia compared with 41 (25%) of 164 participants with older index relatives
(≥60 years), a nonsignificant difference (OR, 0.77; 95% CI, 0.39-1.51).
Other selected patient characteristics are presented in Table 1. There were no significant differences in risk of advanced
neoplasia when whites were compared with blacks and Hispanics. There was no
association between body mass index and risk of advanced neoplasia. A physical
activity index level of greater than 36 was associated with reduced relative
risk of advanced neoplasia (OR, 0.67; 95% CI, 0.49-0.93). Metabolic equivalents
per week did not demonstrate an association with risk. No differences were
found in serum cholesterol levels or rates of cholecystectomy among patients
with vs without advanced neoplasia.
Current smoking (Table 1)
was strongly associated with increased risk (OR, 2.12; 95% CI, 1.49-3.01).
Risk was increased for current users who had more than 25 pack-years of smoking
and for past smokers of more than 49 pack-years before cessation of smoking.
Current alcohol consumption was associated with increased risk if participants
were consuming an average of 1 or more alcoholic drinks per day (OR, 2.12;
95% CI, 1.44-3.14).
Occasional or daily use of NSAIDs was associated with a decreased risk
of advanced neoplasia. When the duration of use was analyzed as a continuous
variable, the age-adjusted OR for advanced neoplasia was strongly associated
with increased duration of use (OR, 0.83 for 10 years of use; 95% CI, 0.73-0.95).
Dietary variables were adjusted for age, total energy consumption, and
medical history risk factors (Table 2).
Total animal fat consumption had a weak, nonsignificant association with advanced
neoplasia. A stronger association was observed for the highest quintile of
fat intake derived from red meat. Participants who consumed beef, pork, or
lamb as a main dish 5 or more times per week had an increased relative risk
of advanced neoplasia compared with those who did not consume these products
(OR, 2.73; 95% CI, 1.05-3.63). Among the components of fiber intake, only
cereal fiber was associated with a reduced relative risk of advanced neoplasia.
Statistically significant reductions in relative risk of advanced neoplasia
were found with increased intake of total calcium, total folate, and vitamin
D in the highest quintile compared with the lowest quintile. Daily consumption
of multivitamins was associated with a significant reduction in risk (OR,
0.75; 95% CI, 0.56-0.99).
Patients with hyperplastic polyps were compared with the cohort with
no polyps (Table 3). There were
no risk variables that distinguished the 2 groups except for past and current
smoking. Past (OR, 1.65; 95% CI, 1.23-2.23) and current (OR, 2.71; 95% CI,
1.93-3.81) smokers had a significantly increased risk of hyperplastic polyps
compared with polyp-free controls. Daily use of NSAIDs was associated with
a decreased OR for hyperplastic polyps (OR, 0.75; 95% CI, 0.56-0.99). When
we compared risk variables in patients with hyperplastic polyps with patients
with advanced neoplasia, results were generally similar to those in patients
with no polyps. Increased age was associated with increased risk of advanced
neoplasia, and higher intake of vitamin D and multivitamins was associated
with a lower risk. Other associations were not statistically significant.
A multivariate model including each medical history factor and 1 factor
from each of the dietary groups was developed (Table 4). Dietary variables were selected statistically by within-category
stepwise regression. This analysis identified cereal fiber, vitamin D, and
beef/pork/lamb as main dish (as percentage of total energy intake) to be the
best candidates for the model. In the multivariate analysis, factors associated
with a significantly increased risk of advanced neoplasia were family history,
current smoking, and moderate to heavy current alcohol use. Risk factors associated
with a significantly decreased risk of advanced neoplasia were use of NSAIDs,
cereal fiber intake, and vitamin D. Vitamin D dominated total calcium and
folate intake in the multivariate analysis. Higher levels of physical activity
were associated with a marginal non–statistically significant reduction
The current study is the first cross-sectional study to assess a wide
range of risk factors for advanced colonic neoplasia in asymptomatic individuals
who have had a complete colon examination. The choice of advanced colonic
neoplasia as the study end point was designed to identify risk factors in
the patients most likely to develop malignancy, with the goal of developing
preventive strategies. This end point has some limitations since many patients
with advanced neoplasia will not develop colon cancer in their lifetime.
Several risk factors were not informative. Prior studies have found
weak associations between colorectal neoplasia risk and body mass index,23,24 serum cholesterol level,25,26 and prior cholecystectomy.27- 29 These variables were
not significantly associated with advanced colonic neoplasia in our study,
but modest associations cannot be excluded.
There was discrepancy between the results of 2 indexes used to assess
physical activity. Patients who scored in the higher range of the physical
activity index, with either longer periods of mild exercise or some heavy
activity, had a lower age-adjusted risk of advanced neoplasia. There was no
difference in risk across quintiles of the metabolic equivalent score. These
findings suggest that individuals may be just as likely to benefit from long
periods of mild physical activity as from shorter periods of heavy activity.
In the multivariate analysis, physical activity had a marginal, non–statistically
The relationship of dietary fat and fiber and colorectal neoplasia is
uncertain. Our analysis found no significant increase in risk of advanced
neoplasia associated with total fat and a marginal, nonsignificant increase
associated with fat derived from red meat sources. Although we did not find
a strong relationship between fat and advanced adenomas, we cannot exclude
the possibility that dietary fat may promote malignant change in precursor
adenomas, thus leading to higher rates of cancer. The current data show that
among the fiber variables, the highest quintiles of cereal fiber intake were
associated with lower risk of advanced neoplasia in the univariate model,
and the relationship remained after adjustments in the multivariate model.
Prior interventional studies with fiber have failed to demonstrate a protective
effect over a 3- to 4-year study period.30,31 However,
these studies used any adenoma (large or small) as an end point and evaluated
a short period of intervention. Our results do not necessarily conflict with
these studies. Our data suggest that higher intake of cereal fiber over a
long period may protect against development of advanced neoplasia.
Vitamin D emerged as an important protective factor. Several prior studies
have suggested that vitamin D and, in particular, its active form (1,25-hydroxyvitamin
D) exerts an antiproliferative effect on colonic mucosa in vitro,32 and several clinical studies have suggested a beneficial
effect.33- 35 Some
prior studies have found a marginal benefit from calcium supplementation in
the prevention of adenomas.36,37 In
our multivariate analysis, dietary vitamin D dominated calcium as a beneficial
risk factor. We did not measure sunlight exposure in our patients, which can
influence 25-hydroxyvitamin D levels. These data suggest that vitamin D may
be an important protective factor, and further study is warranted to determine
the relative contributions of diet vs sunlight. The impact of total folate
and daily multivitamin intake are difficult to separate in the analysis; both
factors were associated with a protective effect in the univariate analysis.
We found that a history of 1 or more first-degree relatives with colorectal
cancer is strongly associated with advanced neoplasia, confirming results
from many other studies.38- 41 When
we compared the risk of advanced neoplasia in participants with family members
diagnosed as having cancer either before or after age 60 years, we did not
find a significant difference. Therefore, our data reinforce recommendations
to treat all patients who have a first-degree relative with colorectal cancer
as a high-risk group and offer screening with colonoscopy.15
Current cigarette smoking and consumption of more than 7 drinks of alcohol
per week were strongly associated with increased risk, consistent with prior
studies.42- 46 Although
the physiologic mechanisms are unclear, these data provide further reason
for health care practitioners to advise smoking cessation and moderation of
Participants taking NSAIDs on a regular basis had a lower risk of advanced
neoplasia compared with those who did not use these drugs, consistent with
many prior studies.47- 51 There
was a strong relationship between duration of drug exposure and reduction
in risk. This study precedes the availability of the cyclooxygenase-2 inhibitor
drugs, which have been shown to reduce the development of adenomas in patients
with familial polyposis.52 More than 80% of
our participants already were taking aspirin as prophylaxis for cardiovascular
disease or other NSAIDs for arthritis and pain. Should adults take NSAIDs
solely for prevention of colonic neoplasia? Some intervention studies have
not shown a benefit.53,54 Moreover,
there are potential harms. The risk of peptic ulcer disease and gastrointestinal
bleeding55 and other health effects must be
balanced against the potential benefits. The decision to begin therapy with
aspirin or other NSAIDs solely for reduction of risk of colonic neoplasia
requires further study.
In a secondary analysis, we determined risk factors in patients whose
most serious colonic lesions were 1 or more hyperplastic polyps. Most guidelines
regard hyperplastic polyps as benign,15 and
several large screening studies have found that distal hyperplastic polyps
are not risk factors for proximal neoplasia.16,56 We
hypothesized that if hyperplastic polyps are incidental, nonneoplastic growths,
patients with hyperplastic polyps should closely resemble patients with no
polyps. No prior study has determined if there are any distinguishing risk
variables for hyperplastic polyps. Our results suggest that patients with
only hyperplastic polyps are similar to polyp-free controls. Only past or
current smoking emerged as a significant risk factor. This is of interest
because smoking is the only risk factor associated with both hyperplastic
polyps and advanced neoplasia. Smoking may promote DNA hypermethylation, and
development of advanced adenomas may depend on methylenetetrahydrofolate reductase
genotype.57 When we compared the advanced neoplasia
cohort to patients with hyperplastic polyps, we found that higher intake of
vitamin D intake and multivitamins was associated with a lower risk of advanced
neoplasia. Other differences were not statistically significant. Since this
was a secondary analysis, our study was not powered to detect such differences.
In addition, patients with advanced neoplasia as their worst lesions may also
have hyperplastic polyps, creating some overlap between groups.
There are several important limitations of our study. First, this is
a cross-sectional study. Some of the purported risk factors may not be associated
with prevalent advanced neoplasia but could be risk factors for subsequent
incident lesions. Follow-up of this population is planned. This analysis focuses on risk factors in a high-risk population with
advanced neoplasia. Cancer progression is not inevitable in this population,
and other factors may promote progression from advanced neoplasia to cancer.
Second, some results may be subject to recall bias. The food frequency questionnaire
has been validated in many studies17,18 but
does not measure whether dietary habits have changed over time. A total of
38.7% of our participants reported a major dietary change over the past 10
years. Similar rates of diet change were found in patients with and without
advanced neoplasia. Therefore, we cannot exclude the possibility that prior
dietary behaviors could have had an effect on current risk of advanced neoplasia.
Third, our results can only be generalized to a male population; further study
of risk factors in women is needed. Also, the veteran population may differ
from other male populations in the United States. Finally, we recognize the
complexity of analyzing confounding variables. Therefore, an important feature
of this study was the inclusion of all major purported historical and dietary
An important strength of this study is that asymptomatic patients had
complete structural examinations of the colon to define the at-risk population,
reducing the likelihood of misclassification. The study was sufficiently powered
to examine a broad range of potentially confounding risk variables.
What new information have we learned from this study? This is one of
the first studies to identify vitamin D as a protective factor. Because vitamin
D and calcium are confounders, only a study of sufficient sample size can
determine the relative benefits of either vitamin D or calcium. We were able
to determine the relative risk and benefit of obesity and exercise. We conclude
that obesity alone is not a significant risk factor and that regular exercise
can be protective. There have been many prior publications citing the benefits
and risks of high-fiber or high-fat diets. Our data suggest that diets high
in cereal fiber are protective and that diets that include large amounts of
fat derived from meat may increase the risk of advanced neoplasia. The risk
associated with smoking and alcohol is now confirmed in a large multivariate
analysis. Many prior studies have analyzed these variables without considering
other risk factors. Finally, we found that patients with hyperplastic polyps
as the most serious finding in the colon closely resemble polyp-free controls.
Past or current smoking was the only significant risk factor for hyperplastic
polyps. This new information is consistent with recommendations to treat hyperplastic
polyps as insignificant colonic lesions.
In conclusion, these results show that several risk factors are positively
associated with prevalence of advanced colonic neoplasia, including family
history of colorectal cancer, current smoking, and current moderate to heavy
alcohol consumption. Factors with an inverse association include use of NSAIDs
and higher levels of consumption of cereal fiber and vitamin D. Marginal,
nonsignificant protective factors were moderate physical activity and total
calcium, total folate, and multivitamin intake.
Our study was not designed to demonstrate that modification of risk
factors can modulate risk of colonic neoplasia. Nevertheless, it is prudent
to recommend that patients stop smoking, reduce alcohol intake, and exercise
regularly as part of general preventive health measures. Consuming vitamin
D plus a calcium supplement or regular dairy products represents a low-risk
strategy that may benefit patients. The benefit of a daily multivitamin is
uncertain and requires further study but is associated with very low risk
to patients. The strong association with family history of colorectal cancer
reinforces existing recommendations to offer screening with colonoscopy. The
potential protective effect of NSAIDs must be carefully balanced against the
risks. Further study is needed to determine if risk factors at baseline colonoscopy
are predictive of future incidence or recurrence of advanced neoplasia.