Tobacco smoking and colorectal cancer: a population-based case-control study in Newfoundland and Labrador.
Zhao, Jinhui ; Halfyard, Beth ; Roebothan, Barbara 等
Globally, colorectal cancer (CRC) is the third leading cause of
death from cancer in males and the fourth leading cause of death from
cancer in females. (1) In 2002, an estimated 1 million new cases of CRC
were diagnosed, accounting for more than 9% of all new cases of cancer.
(2) The incidence of CRC varies around the world: CRC is common in
highly industrialized countries but is much more rare in Asia and
Africa. (1,2)
While research has shown that the incidence of CRC has been
associated with dietary factors (3-5) and physical inactivity, (5,6)
evidence on the relationship between CRC and tobacco use has been
conflicting. A number of epidemiological studies have investigated the
relationship between tobacco smoke and CRC in the last three decades,
but few found a significant risk for CRC among smokers. Earlier studies
found that greater risk of CRC was associated with smoking cigars and
pipes, but not with smoking cigarettes. (7-9) Among studies that
reported an increased risk of CRC with cigarette smoking, the magnitude
of risk was only 1.20-1.40. (10-17) Inadequate adjustment for various
potential confounders such as alcohol, physical activity, body size,
dietary factors, and possibly unidentified confounders could account for
the small increase in risk found with smoking in some studies. In fact,
few potential confounders were adjusted for in most of the cohort
studies. One third of the published studies considered only age or other
relevant demographic factors. (10,11,16,18-24) Some studies adjusted
only for demographic factors and alcohol use, (10,25,26) and less than
half of the studies considered two or more of the potential confounders.
(11,15-17,21,23,27-33) Additionally, evidence of the association of CRC
and smoking by sex, drinking status and subsites of CRC has been
inconsistent.
Newfoundland and Labrador (NL), a province of Canada, has the
highest incidence of CRC in the world. (2,34) Historically, there has
been a relatively high prevalence of tobacco use in the province, with
an average rate of 34% during the period of 1985-2003. (35-38) However,
no studies were conducted to investigate the effect of tobacco smoking
on the risk of developing CRC in NL. Using a population-based
case-control study design, we assessed the relationship between various
measures of smoking and the risk of CRC among NL residents aged 20-74
years, and conducted subgroup analyses by sex, drinking status and
subsites of CRC.
<01_TB005>
METHODS
This study utilized data that had already been collected from an
existing population-based case-control study of more than 4,000
participants from NL and Ontario. Details about this interprovincial CRC
team project can be found elsewhere. (39-46) Briefly, cases were
recruited using the Newfoundland and Labrador Colorectal Cancer Registry
(NFCCR), while controls were random samples of the NL population aged
20-74. (41) Eligible CRC cases were NL residents between 20 and 74 years
old, newly diagnosed with CRC between January 1999 and December 2003,
with histologically confirmed primary adenocarcinoma of the colon or
rectum. Controls were frequency-matched according to sex and 5-year age
group. Self-reported information including personal history, lifestyle
and dietary characteristics were collected using a Personal History
Questionnaire (PHQ) and Food Frequency Questionnaire (FFQ),
respectively, with these questionnaires being developed for and utilized
in the larger study. In addition, a blood sample was provided for
possible genetic analysis. The questionnaires were mailed to all
consenting eligible participants with self-addressed stamped envelopes.
If a participant had not returned finished questionnaires within 3
weeks, a follow-up telephone call was made to ensure that the study
package had been received. A telephone interview or assistance was
offered when illiteracy or physical disability was a concern.
The PHQ consisted of 74 questions, addressing such issues as bowel
screening history, medical conditions, use of medication, diet, physical
activity, consumption of alcohol and tobacco, and socio-demographic
measures such as education and income. As well, demographic information
such as sex, age, date of birth, and marital status was collected. To
define an urban versus rural place of residence, a community with a
population of 10,000 or more was defined as urban, (47) one with less
than 10,000 as rural. Of note, since the town of Gander's
population is slightly under 10,000, it is similar to other urban areas
in NL, and was also defined as urban in this study. For female
participants, there were additional questions relating to reproductive
factors and hormone replacement therapy.
Measurement of exposure
Participants were asked a series of questions on cigarette, cigar
and pipe smoking to determine tobacco-relevant exposures (see Appendix
1). Subjects were classified into three cigarette-smoking categories:
non-smokers, who had not smoked one cigarette a day for 3 months or
longer; former smokers, who had stopped smoking cigarettes about one
year before cancer diagnosis or investigation; and current smokers, who
still smoked at least one cigarette a day during the year prior to
diagnosis or investigation. Other derived variables of cigarette smoking
included age at initiation of smoking (<16 years old and >16);
number of cigarettes smoked per day (<20 cigarettes daily, 20-29 and
[greater than or equal to]30); total number of years of cigarette
smoking (<20 years, 20-29 and >30); years since started smoking
(1-25 years, 26-35 and [greater than or equal to]36) and cigarette pack
years (<20 pack years, 20-39 and [greater than or equal to]40). Pack
years of smoking cigarettes were estimated using the average number of
cigarettes smoked per day, divided by 20, and then multiplied by the
number of years of cigarette smoking. Years of abstention from smoking
cigarettes were also estimated (0 years of abstention from smoking,
1-19, 20-29 and [greater than or equal to]30). Approximately 5% of
subjects had smoked cigars and approximately 10% had smoked pipes;
however, there were no statistically significant relationships between
CRC and cigar or pipe smoking, and thus, the results were not presented
in this paper.
<01_TB006>
Other variables considered in the analyses were: age; sex; region
(urban/rural); birth country; race; education; marital status; alcohol
use; family CRC history (yes/no); other personal cancer history
(yes/no); physician-diagnosed diabetes (yes/no); physician-diagnosed
hypercholesterolemia (yes/no); regular use of aspirin such as Anacin[R],
Bufferin[R], Bayer[R], Excedrin[R], Ecotrin[R] (yes/no); intake of
fruits, vegetables and red meats; body mass index (BMI); physical
activity; lifetime use of bulk-forming laxatives and other laxatives
such as Ex-Lax[R] (yes/no); and lifetime use of calcium pills or tablets
and calcium-based antacids such as Tums[R], Rolaids[R] and
extra-strength Rolaids[R] (yes/no). Intake of fruits/vegetables/red
meats ([less than or equal to]<2 or [greater than or equal to]3
servings daily) was investigated using responses to the questions:
"About one year before [your recent cancer diagnosis]/ [this
survey], on average, how often did you eat a piece or serving of
fruit/vegetables/red meat?" Servings of fruit were defined as: 1
medium-sized fresh fruit; 1/2 cup of chopped, cooked or canned fruit; V
cup of dried fruit; 6 ounces of fruit juice (50-100% pure juice).
Servings of vegetables were defined as: 1 cup raw, leafy vegetables; %
cup of other vegetables, cooked or chopped raw; 6 ounces of vegetable
juice. Red meat servings were defined as 2-3 ounces (a piece of meat
about the size of a deck of cards). Respondents were classified into
physically active and non-physically active groups. Physically active
was defined as participating regularly in physical activities for a
total of at least 30 minutes a week in one's 20s, 30s and 40s, and
50s. Respondents were classified into non-obese (BMI<30) and obese
(BMI>30). BMI was estimated based on the height and weight questions,
"About how tall are you, without your shoes on?" and "How
much did you weigh about one year before your recent cancer diagnosis
(cases) or this survey (controls)?" Subjects were classified as
drinkers if they ever consumed any alcoholic beverages once a week for 6
months or longer. Otherwise they were classified as non-drinkers. The
covariates that were selected for multivariate logistic regression
analyses are presented in Table 1.
Statistical analyses
A descriptive analysis was conducted to present the characteristics
of the sample. The independent effect of cigarette smoking on the
relative risk of CRC was estimated using adjusted odds ratios (OR)
calculated in multivariate binary and multinomial logistic regression
models. (48,49) Each measure of smoking evaluated was modeled
independently from the others given that these measures were highly
correlated. Those who have never smoked served as the reference group in
all analyses. Based on univariate logit analysis of the pooled data set,
any variable whose univariate test had a p-value <0.20 was considered
as a candidate for the multivariate logistic regression analyses. (48)
All selected variables by univariate analysis were included in the
models regardless of their "statistical significance". The
rationale for this approach is to provide as much control of confounding
as possible within the given data set. (48) This is based on the fact
that it is possible for individual variables not to exhibit strong
confounding, but when taken collectively, considerable confounding may
be present in the data. (48) Independent variables with particularly
high inter-correlations (>0.30) were identified and less precise
measures were excluded, (49) and the variable pool was reduced in order
to avoid synonymous variables and collinearity. (50) Data were complete
for approximately 90% of study subjects. For missing data, values were
imputed. The mean of the non-missing values for continuous variables was
used as the estimate of missing continuous data and the mode value is
used as the estimate of missing categorical data. (51) Testing for
linear trends was carried out by representing the categories of exposure
with ordinal variables, considered as continuous, and examining the
significance of the coefficient with a z-test. (52,53) The analyses were
also conducted by sex, drinking status and site of CRC in order to
investigate the modified effects of these factors on the association
between smoking and CRC. (52,53) Population attributable risk (PAR) and
the 95% confidence interval (CI) of PAR were calculated by determining
the 95% CI for log(P [OR-1]) on the basis of the standard errors for P
and OR and transforming back to the 95% CI for the PAR. (54) All
statistical analyses were completed using SAS 9.1. (55) Significance
tests assumed two-tailed p-values or 95% CIs.
<01_TB007>
RESULTS
Characteristics of the cases and controls
A total of 702 CRC cases and 717 controls were included in the
study. The mean age was 60.3 years old (SD: 9.5) for cases and 60.4
years old (SD: 9.4) for controls. Caucasians accounted for over 94% of
the sample and more than 93% of participants were Canadian-born. Over
97% did not have a familial history of CRC. Approximately 13% of the
sample had other cancer diagnosis but there was no significant
difference between cases and controls. The primary results suggested a
significantly increased risk of CRC among those who lived in a rural
area and had lower education. CRC cases tended to be those who had
diabetes and were obese. Having high cholesterol level, taking calcium
pills and tablets, eating more fruits and using aspirin decreased the
risk of CRC. Prevalence of cigarette smoking significantly differed by
most selected covariates (Table 1).
CRC and types of tobacco use
The study found a significant independent association between
smoking cigarettes and CRC (Table 2). There was a 49%, 36% and 96%
higher risk of CRC among all, former and current smokers, respectively,
compared to non-smokers. The adjusted ORs also showed that the risk of
CRC increased significantly with smoking cigarette years, the number of
cigarettes smoked daily, and cigarette pack years. The risk of CRC
decreased significantly with years of abstention from smoking.
<01_TB008>
CRC and cigarette smoking by sex
Cigarette smoking increased the risk of CRC among men and women,
but demonstrated a stronger effect for males than females (Table 3).
Among males: there was a 73%, 64% and 106% higher risk of CRC among all,
former and current cigarette smokers, respectively, compared to
non-smokers; the risk of CRC was significantly increased with smoking
cigarette years, years after smoking began, the number of cigarettes
smoked daily, and cigarette pack years; and the risk significantly
decreased with years of abstention from smoking.
CRC and cigarette smoking by drinking status
Among drinkers, there was a 67% and 133% higher risk of CRC among
former and current smokers, respectively, compared to non-smokers. The
risk of CRC significantly increased with smoking years and decreased
with years of abstention from smoking (Table 4). However, among
non-drinkers, the study only found a weak relationship between smoking
and the risk of CRC.
Colon and rectum cancer and cigarette smoking
The adjusted ORs showed a significant effect of smoking cigarettes
on both colon and rectum cancer (Table 5); however, the adjusted ORs of
subsites for CRC for smokers versus non-smokers demonstrate a stronger
effect of smoking cigarettes on rectum cancer than colon cancer.
DISCUSSION
This population-based case-control study suggests that cigarette
smoking significantly increased the risk of CRC. At a population level,
the estimated population attributable risk of CRC (PAR) associated with
smoking was 13.18% (95% CI 6.80-19.58) in this population. The observed
association was persistent regardless of how tobacco use was defined and
cannot be explained by known confounding factors. Given the
inconsistency in the existing literature around this issue, this study
provides new and important evidence supporting the positive association
between cigarette smoking and CRC. The effects of smoking on CRC seem to
be stronger in males and alcohol drinkers. Smoking also demonstrated a
slightly stronger effect on rectum than colon cancer.
Compared to previous similar studies, (10-17) our study suggests a
stronger association between smoking and CRC. The present study
demonstrated a clear dose-response relationship, showing that the risk
of CRC increased with cigarette smoking years, the amount of cigarettes
smoked per day, and smoking cigarette pack years. This is consistent
with other studies that reported statistically significant dose-response
trends with the amount smoked daily for CRC and its subsites. (10-17.
56-58)
<01_TB009>
Studies on CRC have varied in their assessment of duration of
smoking. Some evidence exists to suggest that the risk for CRC increased
with earlier age at initiation. (11,16) However, our study did not show
this feature. While other studies found a statistically significant
increase of CRC incidence after 30 years of smoking, (59) our study
showed a significantly increased risk after 20 years or more of smoking.
Other studies found that cigarette smoking was unrelated to CRC until 35
years after smoking began, and that the relationship became
progressively more strongly related with time. (29) However, our study
showed that the risk of CRC increased after 25 years since smoking
began, and the risk did not increase with time. These studies and our
study suggest that smoking may act as an initiator of CRC and a longer
induction period may be needed before the association of the cancer with
smoking can be observed.
The benefit of smoking cessation was also evaluated in our study.
The results showed that the risk of CRC significantly decreased with
years of abstention from smoking and there was no significant difference
in the risk between smokers who stopped smoking for 20 years or more and
non-smokers. Other studies also reported a reduced risk of CRC after
years of smoking cessation, but the risk remained substantially elevated
even after 20 years of smoking cessation. (15)
Several cohort studies reported that the association between
smoking and CRC is stronger in men than in women. (12,15,24) However,
one study reported a significantly increased risk associated with
smoking only in women and not in men. (60) Another study showed the
association between smoking and CRC was equally strong in both sexes.
(16) While two case-control studies showed smoking was a risk factor
only in men, (9,61) three case-control studies of those showing smoking
implicated as a risk factor of CRC showed no clear gender differences.
(57,62,63) Our study found an elevated risk related to smoking among men
compared to women. This may be explained by there having been fewer
cigarettes smoked by women or more years of abstention from smoking.
There may be hormone-related differences in susceptibility to smoking.
Our study found that smoking cigarettes demonstrated a stronger
risk of CRC among drinkers than non-drinkers. This combined effect may
be because tobacco smoke is a major source of a wide variety of
carcinogens including heterocyclic hydrocarbons and nitromines, and
alcohol might serve as a solvent for polycyclic aromatic hydrocarbons
and similar organic compounds from cigarettes, transporting these
chemicals to sites they otherwise would not reach. (64,65)
Smoking cigarettes in our study demonstrated a slightly stronger
effect on the risk of rectum cancer compared to colon cancer. This
result is consistent with previous studies. (12-14,27,66,67) The
biological mechanism behind this subsite specificity is unknown, but
differences in the embryonic tissues of the colon and rectum and in
patterns of growth factors and receptors may be relevant. (10,68,69)
Also, nicotine may have a differential effect on the colon and rectum,
enhancing motility in the colon, but not in the rectum.21 Tobacco
carcinogens may be more concentrated in the rectum than in the colon.
(69,70)
Possible biological mechanisms relating to the cause of CRC may
involve the exposure of the epithelium of the large bowel to carcinogens
either via the blood circulation after absorption of these chemicals in
the lung, or after ingestion of saliva contaminated by tobacco smoke.
(29,71) Tobacco smoke contains at least 50 carcinogenic components, the
most genotoxic of which are thought to be the polycyclic aromatic
hydrocarbons, heterocyclic aromatic amines, and N-nitroso compounds.72
These compounds require bioactivation before they can form adducts with
DNA. Polycyclic aromatic hydrocarbons are activated mainly by
extra-hepatic enzymes [e.g., cytochrome P450 (CYP1A1) and microsomal
epoxide hydrolase (mEH)], whereas heterocyclic aromatic amines are
activated in the liver by CYP1A2, and N-nitroso compounds are activated
by hepatic CYP2E1 and CYP2A6. (72) Polymorphisms in mEH have been
associated with CRC in the presence of smoking. (73,74) The Mspl CYP1A1
variant rare allele gives rise to increased levels of the main enzyme
involved in the activation of polycyclic aromatic hydrocarbons and was
found to be related to higher risk for colon or rectum cancer. (74,75)
This study is subject to several limitations. First, despite our
best efforts, the participation rates of both cases and control subjects
were relatively low (59.6% and 44.7%, respectively), in particular that
of the controls. It is possible that study respondents and
nonrespondents differed by certain characteristics (e.g., smoking and
drinking). However, our analysis (another prepared paper) on
nonparticipation bias of the cases did not show evidence that
nonparticipation greatly affects the results of the study. An evaluation
of the low participation rate in controls in this study suggested that
participating controls tended to have a higher socio-economic status and
lower smoking prevalence than the province's general population,
which may have led to an overestimation of the true effects of smoking.
(41) Second, our study was not free from recall bias. Cases may have
been more likely than controls to recall smoking behaviour, trying to
attribute their diagnosis to their past behaviour. The main protection
against this was the standardization of methods, therefore the questions
were identical and were presented in an identical fashion to both cases
and controls. Analyses (another prepared paper) conducted to assess the
validity and reliability of self-reporting lifetime tobacco use for this
study did not suggest that inaccurate or differential reporting of
smoking for cases and controls may have biased the association greatly.
Third, our study included 258 deceased cases; of these, 143 died before
the survey was conducted. The response from proxies of these deceased
cases might differ from those of living cases, possibly biasing the
results. However, examination of the estimates of the risk of living and
deceased cases did not show any difference. Finally, while our study
could not assess how other unknown confounders affected the observed
association, a recent review suggests that confounding is not important.
(76)
In conclusion, this study found that there was a higher risk of CRC
among former and current smokers than non-smokers. The association
showed a clear dose-response relationship with the risk of CRC
increasing with cigarette smoking years, the number of cigarettes smoked
daily, and cigarette pack years, and a decrease in risk with more years
of abstention from smoking. This association was stronger among drinkers
and in men. In addition, this effect was observed to be slightly
stronger for rectum compared to colon cancer.
Appendix 1. Questions on tobacco smoking in the NL Population-based
case-control study of CRC
Q1. Have you ever smoked at least one cigarette a day for 3 months
or longer?
* yes * no [right arrow] Please go to #64 * don't know [right
arrow] Please go to #64
Q1a. When did you first start smoking at least one cigarette a day?
* age at first use or__ year of first use * don't know
Q1b. During periods when you smoked regularly, how many cigarettes
did you typically smoke in a day? __cigarettes per day * don't know
Q1c. About one year before your recent cancer diagnosis, were you
still smoking at least one cigarette a day?
* yes no don't know
Q1d. Do you still smoke at least one cigarette a day?
* yes no [right arrow] Please go to #63f don't know [right
arrow] Please go to #63f
Q1e. When did you stop smoking at least one cigarette a day
(meaning stop smoking permanently)?
__age at first use or__year of first use * don't know
Q1f. How many years, in total, did you smoke at least one cigarette
a day for 3 months or longer? (If you have stopped and restarted at
least once, count only the time when you were smoking.) _total number of
years * don't know
Q2. Have you ever smoked at least one cigar a month for at least 3
months?
* yes no [right arrow] Please go to #65 * don't know [right
arrow] Please go to #65
Q2a. When did you first start smoking at least one cigar a month?
__age at first use or__year of first use * don't know
Q2b. During periods when you smoked regularly, how many cigars did
you typically smoke in a month? __cigars per month * don't know
Q2c. About one year before your recent cancer diagnosis, were you
still smoking at least one cigar a month?
* yes * no * don't know
Q2d. Do you still smoke at least one cigar a month?
* yes * no [right arrow] Please go to #64f * don't know [right
arrow] Please go to #64f
Q2e. When did you stop smoking at least one cigar a month (meaning
stop smoking permanently)?
__age at first use or__year of first use don't know
Q2f. How many years, in total, did you smoke at least one cigar a
month for 3 months or longer? (If you have stopped and restarted at
least once, count only the time when you were smoking.) __total number
of years * don't know
Q3. Have you ever smoked at least one pipe a month for at least 3
months?
* yes * no [right arrow] Please go to #66 * don't know [right
arrow] Please go to #66
Q3a. When did you first start smoking at least one pipe a month?
__age at first use or__year of first use * don't know
Q3b. During periods when you smoked regularly, how many pipes did
you typically smoke in a month? __pipes per month * don't know
Q3c. About one year before your recent cancer diagnosis, were you
still smoking at least one pipe a month?
* yes * no * don't know
Q3d. Do you still smoke at least one pipe a month?
* yes * no [right arrow] Please go to #65f * don't know [right
arrow] Please go to #65f
Q3e. When did you stop smoking at least one pipe a month (meaning
stop smoking permanently)?
__age at first use or__year of first use * don't know
Q3f. How many years, in total, did you smoke at least one pipe a
month for 3 months or longer? (If you have stopped and restarted at
least once, count only the time when you were smoking.) __total number
of years * don't know
Received: October 19, 2009
Accepted: April 5, 2010
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Jinhui Zhao, MD, MSc, [1] Beth Halfyard, MSc, [1] Barbara
Roebothan, PhD, [1] Roy West, PhD, [1] Sharon Buehler, PhD, [1] Zhuoyu
Sun, MSc, [1] Joshua Squires, MSc, [1] John R. Mclaughlin, PhD, [2,3]
Patrick S. Parfrey, MD, [4] Peizhong Peter Wang, MD, PhD [1,5]
Author Affiliations
[1.] Division of Community Health and Humanities, Faculty of
Medicine, Memorial University of Newfoundland, St. John's, NL
[2.] Population Studies and Surveillance, Cancer Care Ontario,
Toronto, ON
[3.] Samuel Lunenfeld Research Institute, Mount Sinai Hospital,
Toronto, ON
[4.] Clinical Epidemiology Unit, Faculty of Medicine, Memorial
University of Newfoundland, St. John's, NL
[5.] School of Public Health, Tianjin Medical University, Tianjin,
China
Correspondence: Peizhong Peter Wang, Division of Community Health
& Humanities, Faculty of Medicine, Memorial University of
Newfoundland, St. John's, NL A1B 3V6, Tel: 709-777-8571, Fax:
709-777-7382, E-mail: pwang@mun.ca This work was supported by Canadian
Institutes of Health Research grants (#FRN79845 and CRT-43821) to the
CIHR Team for Interdisciplinary Research on Colorectal Cancer.
Conflict of Interest: None to declare.
Table 1. Characteristics of CRC Cases and Controls and Prevalence
Rates of Cigarette Smoking by Selected Variables of Demographics,
Chronic Conditions, Medication and Lifestyles in the NL
Population-based Case-control Study of CRC in 1999-2003
Demographics Case Control
N %([dagger]) N %t
Age group (years)
20-54 186 26.50 185 25.80
55-64 242 34.47 264 36.82
65-74 274 39.03 268 37.38
Sex
Female 276 39.32 293 40.86
Male 426 60.68 424 59.14
Region *
Urban 302 43.02 353 49.23
Rural 400 56.98 364 50.77
Education ***
High school or less 446 63.53 349 48.68
College+ 256 36.47 368 51.32
Marital status
Married 540 76.92 579 80.75
Single/div/sep/wid 162 23.08 138 19.25
Diabetes ***
No 555 79.06 623 86.89
Yes 147 20.94 94 13.11
Use of laxatives ***
No 573 81.62 657 91.63
Yes 129 18.38 60 8.37
Obesity *
No (BMI<30) 503 71.65 556 77.55
Yes (BMI [greater
than or equal to]
30) 199 28.35 161 22.45
Alcohol once/week
No 270 38.46 264 36.82
Yes 432 61.54 453 63.18
Cholesterol level **
Low 494 70.37 451 62.90
High 208 29.63 266 37.10
Aspirin *
No 522 74.62 492 68.62
Yes 180 25.38 225 31.38
Fruits daily ***
1-2 servings 519 73.93 471 65.69
[greater than or
equal to] 3
servings 183 26.07 246 34.31
Calcium supplement ***
No 608 86.61 568 79.22
Yes 94 13.39 149 20.78
Demographics OR for Covariates
%([dagger]) 95% CI
Age group (years)
20-54 1.00
55-64 0.91 0.70-1.19
65-74 1.02 0.78-1.32
Sex
Female 1.00
Male 1.07 0.86-1.32
Region
Urban 1.00
Rural 1.28 1.04-1.58 *
Education
High school or less 1.00
College+ 0.54 0.44-0.67 ***
Marital status
Married 1.00
Single/div/sep/wid 0.80 0.62-1.03
Diabetes
No 1.00
Yes 1.76 1.32-2.33 ***
Use of laxatives
No 1.00
Yes 2.47 1.78-3.42 ***
Obesity
No (BMI<30) 1.00
Yes (BMI [greater
than or equal to]
30) 1.37 1.07-1.74 *
Alcohol once/week
No 1.00
Yes 0.93 0.75-1.16
Cholesterol level
Low 1.00
High 0.72 0.57-0.89 **
Aspirin
No 1.00
Yes 0.75 0.60-0.95 *
Fruits daily
1-2 servings 1.00
[greater than or
equal to] 3
servings 0.68 0.54-0.85 ***
Calcium supplement
No 1.00
Yes 0.60 0.44-0.78 ***
Demographics Cigarette smoking ([double dagger])
N % 95% CI
Age group (years)
20-54 230 61.99 57.05-66.94
55-64 344 67.98 63.91-72.05
65-74 374 69.00 65.91-72.05
Sex [DELTA]
Female 303 53.25 49.15-57.36
Male 645 75.88 73.00-78.76
Region
Urban 432 65.95 62.32-69.58
Rural 516 67.54 64.22-70.86
Education [DELTA]
High school or less 563 70.82 67.65-73.98
College+ 385 61.70 57.88-65.52
Marital status
Married 757 67.65 64.91-70.39
Single/div/sep/wid 191 63.67 58.22-69.12
Diabetes [DELTA]
No 769 65.28 62.56-68.00
Yes 179 74.28 68.74-79.80
Use of laxatives
No 823 66.91 64.28-69.54
Yes 125 66.14 59.38-72.89
Obesity
No (BMI<30) 693 65.44 62.57-68.31
Yes (BMI [greater
than or equal to]
30) 255 70.83 66.13-75.53
Alcohol once/week [DELTA]
No 260 48.69 44.44-52.93
Yes 688 77.74 75.00-80.48
Cholesterol level [DELTA]
Low 612 64.70 61.71-67.81
High 336 70.89 66.79-74.98
Aspirin [DELTA]
No 649 64.00 61.05-66.96
Yes 299 73.83 69.54-78.11
Fruits daily [DELTA]
1-2 servings 679 68.59 65.69-71.48
[greater than or
equal to] 3
servings 269 62.70 58.12-67.29
Calcium supplement [DELTA]
No 811 68.96 66.31-71.61
Yes 137 56.38 50.14-62.62
([dagger]) Column % and Unadjusted OR and [X.sup.2] and Wald test: *
p<0.05 ** p<0.01 *** p<0.001.
([double dagger]) Number, percentage of smokers and 95% CI of the
percentage.
([DELTA] shows a significant difference between subgroups.
Table 2. OR of CRC and Corresponding 95% CI for Cigarette Smoke in the
NL Population-based Case-control Study of CRC in 1999-2003
Tobacco Measure Case Control
N % N %
Cigarette smoke ***
Non-smoker 201 28.63 270 37.66
Smoker 501 71.37 447 62.34
Cigarette status ***
Former 352 50.14 351 48.95
Current 149 21.23 96 13.39
Cigarette age **
<16 172 24.50 153 21.34
[greater than
or equal to]
16 329 46.87 294 41.00
P-trend
Cigarette years ***
<20 119 16.95 150 20.92
20-29 136 19.37 113 15.76
[greater than
or equal to]
30 246 35.04 184 25.66
P-trend
Years since
initiation **
1-25 36 5.13 26 3.63
26-35 89 12.68 72 10.04
[greater than
or equal to]
36 376 53.56 349 48.68
P-trend
Cigarettes daily **
<20 234 33.33 216 30.13
20-29 193 27.49 175 24.41
[greater than
or equal to]
30 74 10.54 56 7.81
P-trend
Pack years ***
<20 198 28.21 201 28.03
20-39 172 24.50 146 20.36
[greater than
or equal to]
40 131 18.66 100 13.95
P-trend
Years of abstention ***
0 149 21.23 96 13.39
<20 193 27.49 156 21.76
20-29 96 13.68 94 13.11
[greater than
or equal to]
30 63 8.97 101 14.09
P-trend
Tobacco Measure Unadjusted Adjustedt
OR 95% CI OR 95% CI
Cigarette smoke
Non-smoker 1.00 1.00
Smoker 1.51 1.20-1.88 *** 1.49 1.16-1.92 ***
Cigarette status
Former 1.35 1.06-1.70 * 1.36 1.04-1.77 *
Current 2.08 1.52-2.86 *** 1.96 1.40-2.76 ***
Cigarette age
<16 1.51 1.14-2.01 ** 1.47 1.07-2.03 *
[greater than
or equal to]
16 1.50 1.18-1.92 *** 1.50 1.15-1.66 **
P-trend **
Cigarette years
<20 1.07 0.79-1.44 1.15 0.83-1.59
20-29 1.62 1.20-2.20 ** 1.62 1.16-2.28 **
[greater than
or equal to]
30 1.80 1.38-2.34 *** 1.71 1.27-2.30 **
P-trend **
Years since
initiation
1-25 1.86 1.09-3.18 * 1.67 0.95-2.95
26-35 1.66 1.16-2.38 ** 1.62 1.07-2.47 *
[greater than
or equal to]
36 1.45 1.15-1.83 ** 1.44 1.10-1.89 *
P-trend ns
Cigarettes daily
<20 1.46 1.12-1.89 ** 1.45 1.10-1.92 *
20-29 1.48 1.13-1.95 ** 1.51 1.11-2.05 *
[greater than
or equal to]
30 1.78 1.20-2.63 ** 1.67 1.07-2.58 *
P-trend *
Pack years
<20 1.32 1.01-1.73 * 1.36 1.03-1.82 *
20-39 1.58 1.19-2.11 ** 1.60 1.11-2.19 **
[greater than
or equal to]
40 1.76 1.28-2.42 *** 1.64 1.14-2.36 *
P-trend **
Years of abstention
0 2.08 1.52-2.86 *** 1.97 1.40-2.77 ***
<20 1.66 1.26-2.20 *** 1.61 1.19-2.19 *
20-29 1.37 0.98-1.92 1.37 0.95-1.99
[greater than
or equal to]
30 0.84 0.58-1.21 0.90 0.60-1.33
P-trend ***
Note: ([dagger]) OR estimates for cigarette smoke from binary logistic
models adjusted for age, sex, education, marital status, rural-urban,
diabetes, cholesterol, aspirin, alcohol use, BMI, fruits, laxatives
and calcium. [X.sup.2] or Wald test or Cochran-Armitage test for
trend: * p<0.05 ** p<0.01 *** p<0.001. Cochran-Armitage test for
trend: ns=not significant at 5%.
Table 3. Adjusted OR of CRC and Corresponding 95% CI for Cigarette
Smoke in Men and Women in the NL Population-based Case-control Study
of CRC in 1999-2003
Tobacco Measure Men
Case Control OR 95% CI ([dagger])
Cigarette smoke ***
Non-smoker 81 124 1.00
Smoker 345 300 1.73 1.22-2.46 **
Cigarette status ***
Former 254 238 1.64 1.13-2.36 *
Current 91 62 2.06 1.30-3.27 ***
Cigarette age **
<16 137 126 1.61 1.07-2.42 *
[greater than
or equal to]
16 208 174 1.81 1.24-2.65 **
P-trend **
Cigarette years **
<20 91 91 1.61 1.04-2.47 *
20-29 88 77 1.73 1.10-2.72 *
[greater than
or equal to]
30 166 132 1.84 1.23-2.76 **
P-trend *
Years since
initiation **
1-25 15 14 1.54 0.67-3.54
26-35 53 42 1.67 0.94-2.98
[greater than
or equal to]
36 277 244 1.76 1.21-2.56 **
P-trend *
Cigarettes daily **
<20 127 115 1.72 1.15-2.59 **
20-29 149 133 1.71 1.15-2.56 *
[greater than
or equal to]
30 69 52 1.79 1.09-2.95 *
P-trend *
Pack years **
<20 121 115 1.70 1.13-2.55 *
20-39 111 98 1.64 1.07-2.52 *
[greater than
or equal to]
40 113 87 1.89 1.21-2.93 *
P-trend *
Years of
abstention ***
0 91 62 2.07 1.31-3.29 ***
<20 124 106 1.71 1.13-2.61 *
20-29 77 64 1.88 1.18-3.01 **
[greater than
or equal to]
30 53 68 1.27 0.77-2.10
P-trend ***
Tobacco Measure Women
Case Control OR 95% CI ([dagger])
Cigarette smoke
Non-smoker 120 146 1.00
Smoker 156 147 1.21 0.83-1.75
Cigarette status **
Former 98 113 1.07 0.72-1.60
Current 58 34 1.85 1.09-3.13 *
Cigarette age **
<16 35 27 1.50 0.80-2.80
[greater than
or equal to]
16 121 120 1.15 0.78-1.69
P-trend ns
Cigarette years ***
<20 28 59 0.62 0.36-1.07
20-29 48 36 1.66 0.97-2.85
[greater than
or equal to]
30 80 52 1.70 1.07-2.70 **
P-trend *
Years since
initiation
1-25 21 12 1.75 0.79-3.89
26-35 36 30 1.57 0.84-2.92
[greater than
or equal to]
36 99 105 1.13 0.75-1.70
P-trend ns
Cigarettes daily
<20 107 101 1.16 0.77-1.74
20-29 44 42 1.27 0.74-2.17
[greater than
or equal to]
30 5 4 1.91 0.42-8.66
P-trend ns
Pack years
<20 77 86 1.03 0.66-1.59
20-39 61 48 1.55 0.94-2.54
[greater than
or equal to]
40 18 13 1.15 0.50-2.64
P-trend ns
Years of
abstention ***
0 58 34 1.79 1.05-3.05 *
<20 69 50 1.60 0.98-2.60
20-29 19 30 0.71 0.36-1.42
[greater than
or equal to]
30 10 33 0.41 0.18-0.93 *
P-trend ns
Note: ([dagger]) OR for cigarette smoke from binary logistic
regression models adjusted for age, education, marital status, rural-
urban, diabetes, cholesterol, aspirin, alcohol use, BMI, fruits,
hormone replacement (in women), laxatives and calcium. [X.sup.2] or
Wald test or Cochran-Armitage test for trend: * p<0.05 ** p<0.01 ***
p<0.001. Cochran-Armitage test for trend: ns=not significant at 5%.
Table 4. Adjusted OR of CRC and Corresponding 95% CI for Cigarette
Smoke among Drinkers and Non-drinkers in the NL Population-based
Case-control Study of CRC in 1999-2003
Tobacco Measure Drinkers
Case Control OR ([dagger]) 95% CI
Cigarette smoke ***
Non-smoker 70 127 1.00
Smoker 362 326 1.82 1.28-2.58 **
Cigarette status ***
Former 259 257 1.67 1.16-2.58 *
Current 103 69 2.33 1.49-3.65 **
Cigarette age ***
<16 136 124 1.68 1.11-2.54
[greater than
or equal to]
16 226 202 1.89 1.31-2.74 **
P-trend **
Cigarette years ***
<20 89 106 1.47 0.96-2.25
20-29 98 83 2.07 1.33-3.21 **
[greater than
or equal to]
30 175 137 1.96 1.32-2.93 **
P-trend **
Years since
initiation ***
1-25 24 19 1.99 0.97-4.04
26-35 68 58 1.87 1.12-3.14 *
[greater than
or equal to]
36 270 249 1.78 1.22-2.59 **
P-trend ns
Cigarettes daily ***
<20 159 134 2.03 1.37-3.00 *
20-29 141 146 1.58 1.06-2.36 *
[greater than
or equal to]
30 62 46 1.91 1.13-3.23 *
P-trend ns
Pack years ***
<20 143 139 1.79 1.21-2.66 *
20-39 120 106 1.90 1.25-2.89 *
[greater than
or equal to]
40 99 81 1.73 1.10-2.74 *
P-trend ns
Years of
abstention ***
0 103 69 2.34 1.50-3.67 **
<20 141 119 1.87 1.25-2.81 *
20-29 72 70 1.71 1.07-2.73 *
[greater than
or equal to]
30 46 68 1.19 0.71-2.00
P-trend ***
Tobacco Measure Non-drinkers
Case Control OR ([dagger]) 95% CI
Cigarette smoke
Non-smoker 131 143 1.00
Smoker 139 121 1.18 0.81-1.70
Cigarette status *
Former 93 94 1.05 0.57-1.69
Current 46 27 1.57 0.89-2.75
Cigarette age
<16 36 29 1.36 0.75-2.45
[greater than
or equal to]
16 103 92 1.12 0.76-1.67
P-trend ns
Cigarette years *
<20 30 44 0.77 0.44-1.34
20-29 38 30 1.23 0.69-2.19
[greater than
or equal to]
30 71 47 1.51 0.94-2.41
P-trend ns
Years since
initiation
1-25 12 7 1.38 0.50-3.80
26-35 21 14 1.48 0.66-3.33
[greater than
or equal to]
36 106 100 1.09 0.73-1.64
P-trend ns
Cigarettes daily
<20 75 82 0.89 0.58-1.36
20-29 52 29 1.99 1.14-3.48
[greater than
or equal to]
30 12 10 1.47 0.56-3.85
P-trend ns
Pack years
<20 55 62 0.89 0.56-1.41
20-39 52 40 1.39 0.83-2.32
[greater than
or equal to]
40 32 19 1.78 0.90-3.50
P-trend ns
Years of
abstention **
0 46 27 1.55 0.88-2.72
<20 52 37 1.43 0.85-2.41
20-29 24 24 1.09 0.56-2.11
[greater than
or equal to]
30 17 33 0.55 0.28-1.09
P-trend ns
Note: ([ddegrees]) OR for cigarette smoke from binary logistic
regression models adjusted for age, sex, education, marital status,
rural-urban, diabetes, cholesterol, aspirin, alcohol use, BMI, fruits,
laxatives and calcium. [X.sup.2] or Wald test or Cochran-Armitage test
for trend: * p<0.05 ** p<0.01 *** p<0.001. Cochran-Armitage test for
trend: ns=not significant at 5%.
Table 5. Adjusted OR of Colon and Rectum Cancer and Corresponding 95%
CI for Cigarette Smoke in the NL Population-based Case-control Study
of CRC in 1999-2003
Tobacco Measure Control Colon Cancer
Case OR ([dagger]) 95% CI
Cigarette smoke ***
Non-smoker 270 140 1.00
Smoker 447 330 1.49 1.12-1.97 *
Cigarette status ***
Former 351 243 1.41 1.01-2.05 *
Current 96 87 1.70 1.15-2.98 *
Cigarette age **
<16 153 116 1.54 1.07-2.20 *
[greater than
or equal to]
16 294 214 1.47 1.09-1.98 *
P-trend *
Cigarette years ***
<20 150 73 1.08 0.76-1.83
20-29 113 94 1.72 1.17-2.87 **
[greater than
or equal to]
30 184 163 1.70 1.09-2.45 *
P-trend **
Years since
initiation ***
1-25 26 24 1.65 0.88-3.09
26-35 72 52 1.52 0.95-2.44
[greater than
or equal to]
36 349 254 1.44 1.06-1.94 *
P-trend ns
Cigarettes daily **
<20 216 161 1.44 1.05-1.98 *
20-29 175 122 1.48 1.05-2.10 *
[greater than
or equal to]
30 56 47 1.66 1.01-2.71 *
P-trend *
Pack years **
<20 201 124 1.27 0.92-1.76
20-39 146 117 1.70 1.20-2.40 *
[greater than
or equal to]
40 100 89 1.72 1.15-2.58 *
P-trend **
Years of
abstention ***
0 96 87 1.76 1.20-2.58 **
<20 156 142 1.81 1.29-2.54 **
20-29 94 56 1.22 0.80-1.85
[greater than
or equal to]
30 101 45 0.95 0.61-1.49
P-trend **
Tobacco Measure Rectum Cancer
Case OR ([dagger]) 95% CI
Cigarette smoke
Non-smoker 61 1.00
Smoker 171 1.56 1.09-2.25 *
Cigarette status
Former 109 1.31 0.89-1.93
Current 62 2.41 1.52-3.83 ***
Cigarette age
<16 56 1.36 0.86-2.15
[greater than
or equal to]
16 115 1.66 1.13-2.43 **
P-trend *
Cigarette years
<20 46 1.36 0.85-2.16
20-29 42 1.53 0.94-2.48
[greater than
or equal to]
30 83 1.78 1.16-2.72 *
P-trend *
Years since
initiation
1-25 12 1.67 0.77-3.64
26-35 37 1.83 1.05-3.19 *
[greater than
or equal to]
36 122 1.48 0.99-2.20
P-trend ns
Cigarettes daily
<20 73 1.46 0.97-2.20
20-29 71 1.67 1.08-2.58 *
[greater than
or equal to]
30 27 1.75 0.96-3.18
P-trend *
Pack years
<20 74 1.58 1.04-2.39 *
20-39 55 1.56 0.99-2.44
[greater than
or equal to]
40 42 1.54 0.92-2.57
P-trend ns
Years of
abstention
0 62 2.43 1.53-3.86 ***
<20 51 1.29 0.82-2.03
20-29 40 1.79 1.08-2.95 *
[greater than
or equal to]
30 18 0.86 0.46-1.59
P-trend ***
Note: ([dagger]) OR for cigarette smoke from logistic regression
models was adjusted for age, sex, education, marital status,
rural-urban, diabetes, cholesterol, aspirin, alcohol use, BMI, fruits,
laxatives and calcium. [X.sup.2] or Wald test or Cochran-Armitage test
for trend: * p<0.05 ** p<0.01 *** p<0.001. Cochran-Armitage test for
trend: ns=not significant at 5%.
