Group Title: BMC Cancer
Title: Smoking, environmental tobacco smoke, and risk of renal cell cancer: a population-based case-control study
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Title: Smoking, environmental tobacco smoke, and risk of renal cell cancer: a population-based case-control study
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Language: English
Creator: Theis, Ryan
Dolwick Grieb, Suzanne
Burr, Deborah
Siddiqui, Tariq
Asal, Nabih
Publisher: BMC Cancer
Publication Date: 2008
 Notes
Abstract: BACKGROUND:Kidney and renal pelvis cancers account for 4% of all new cancer cases in the United States, among which 85% are renal cell carcinomas (RCC). While cigarette smoking is an established risk factor for RCC, little is known about the contribution of environmental tobacco smoke (ETS) to RCC incidence. This study assesses the role of smoking and ETS on RCC incidence using a population-based case-control design in Florida and Georgia.METHODS:Incident cases (n = 335) were identified from hospital records and the Florida cancer registry, and population controls (n = 337) frequency-matched by age (+/- 5 years), gender, and race were identified through random-digit dialing. In-person interviews assessed smoking history and lifetime exposure to ETS at home, work, and public spaces. Home ETS was measured in both years and hours of exposure. Odds ratios and 95% confidence intervals were calculated using logistic regression, controlled for age, gender, race, and BMI.RESULTS:Cases were more likely to have smoked 20 or more pack-years, compared with never-smokers (OR: 1.35, 95% CI: 0.93 – 1.95). A protective effect was found for smoking cessation, beginning with 11–20 years of cessation (OR: 0.39, 95% CI: 0.18–0.85) and ending with 51 or more years of cessation (OR: 0.11, 95% CI: 0.03–0.39) in comparison with those having quit for 1–10 years. Among never-smokers, cases were more likely to report home ETS exposure of greater than 20 years, compared with those never exposed to home ETS (OR: 2.18; 95% CI: 1.14–4.18). Home ETS associations were comparable when measured in lifetime hours of exposure, with cases more likely to report 30,000 or more hours of home ETS exposure (OR: 2.37; 95% CI: 1.20–4.69). Highest quartiles of combined home/work ETS exposure among never-smokers, especially with public ETS exposure, increased RCC risk by 2 to 4 times.CONCLUSION:These findings confirm known associations between smoking and RCC and establish a potential etiologic role for ETS, particularly in the home. Differences in methods of retrospective measurement of lifetime smoking and ETS exposure may contribute to discrepancies in measures of associations across studies, and should be addressed in future research.
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Research article

Smoking, environmental tobacco smoke, and risk of renal cell
cancer: a population-based case-control study
Ryan P Theis*1, Suzanne M Dolwick Grieb2, Deborah Burr2, Tariq Siddiqui3
and Nabih R Asal2


Address: 'Department of Epidemiology and Health Policy Research, College of Medicine, University of Florida, Florida, USA, 2Department of
Epidemiology and Biostatistics, College of Public Health and Health Professions, University of Florida, Florida, USA and 3Hematology and
Oncology Division, Department of Medicine, College of Medicine, University of Florida, Florida, USA
Email: Ryan P Theis* rtheis@ichp.ufl.edu; Suzanne M Dolwick Grieb sdolwick@ufl.edu; Deborah Burr burr@stat.ufl.edu;
Tariq Siddiqui siddit@medicine.ufl.edu; Nabih R Asal asal@phhp.ufl.edu
* Corresponding author



Published: 24 December 2008 Received: 16 June 2008
BMC Cancer 2008, 8:387 doi:10.1 186/1471-2407-8-387 Accepted: 24 December 2008
This article is available from: http://www.biomedcentral.com/1471-2407/8/387
2008 Theis et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.ore/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Abstract
Background: Kidney and renal pelvis cancers account for 4% of all new cancer cases in the United
States, among which 85% are renal cell carcinomas (RCC). While cigarette smoking is an
established risk factor for RCC, little is known about the contribution of environmental tobacco
smoke (ETS) to RCC incidence. This study assesses the role of smoking and ETS on RCC incidence
using a population-based case-control design in Florida and Georgia.
Methods: Incident cases (n = 335) were identified from hospital records and the Florida cancer
registry, and population controls (n = 337) frequency-matched by age (+/- 5 years), gender, and
race were identified through random-digit dialing. In-person interviews assessed smoking history
and lifetime exposure to ETS at home, work, and public spaces. Home ETS was measured in both
years and hours of exposure. Odds ratios and 95% confidence intervals were calculated using
logistic regression, controlled for age, gender, race, and BMI.
Results: Cases were more likely to have smoked 20 or more pack-years, compared with never-
smokers (OR: 1.35, 95% Cl: 0.93 1.95). A protective effect was found for smoking cessation,
beginning with I 1-20 years of cessation (OR: 0.39, 95% Cl: 0.18-0.85) and ending with 51 or more
years of cessation (OR: 0.1 I, 95% Cl: 0.03-0.39) in comparison with those having quit for 1-10
years. Among never-smokers, cases were more likely to report home ETS exposure of greater than
20 years, compared with those never exposed to home ETS (OR: 2.18; 95% Cl: 1.14-4.18). Home
ETS associations were comparable when measured in lifetime hours of exposure, with cases more
likely to report 30,000 or more hours of home ETS exposure (OR: 2.37; 95% Cl: 1.20-4.69).
Highest quartiles of combined homework ETS exposure among never-smokers, especially with
public ETS exposure, increased RCC risk by 2 to 4 times.
Conclusion: These findings confirm known associations between smoking and RCC and establish
a potential etiologic role for ETS, particularly in the home. Differences in methods of retrospective
measurement of lifetime smoking and ETS exposure may contribute to discrepancies in measures
of associations across studies, and should be addressed in future research.



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Background
Kidney and renal pelvis cancers account for nearly 4% of
all new cancer cases in the United States, with 54,390 new
cases estimated for the year 2008 [1,2]. Incidence rates
have almost doubled over the past 30 years from 7.1 per
100,000 in 1975 to 13.4 per 100,000 in 2005 [1]. Most of
these cases are renal cell carcinomas (RCC), accounting
for approximately 85% of all renal tumors [3]. Known
genetic predispositions explain 2% of RCC cases [3], sug-
gesting that increases in incidence are due largely to envi-
ronmental factors.

The association between RCC and cigarette smoking is well
established, although reported risk increases for ever-smok-
ers compared with never-smokers are moderate. In a recent
meta-analysis, ever-smoking produced a relative risk for
RCC of 1.38, and risk increases were generally greater
among men (RR = 1.50) than women (RR = 1.27) [4].
Despite these modest risk increases, dose-response associa-
tions and cessation effects have been consistently reported.
The International Agency for Research on Cancer has con-
cluded that sufficient evidence exists for a causal associa-
tion between cigarette smoking and RCC [5].

Few studies have explored the potential associations
between environmental tobacco smoke (ETS) and RCC
[6,7]. The Surgeon General's most recent report on invol-
untary tobacco smoke concluded that living with a
smoker increases lung cancer risk by 20 to 30%, and that
ETS may also contribute to cancers of the breast and nasal
sinus cavity [8]. A case-control study of passive smoking
and overall cancer risk found that individuals ever mar-
ried to smokers were 1.6 times more likely than those
never married to smokers to develop cancer at any site [9].

The present paper reports findings from a population-
based case-control study of RCC in Florida and Georgia,
evaluating the role of tobacco smoke exposure for ciga-
rettes and ETS including duration of ETS exposure in the
home, workplace, and in other public or private locations.

Methods
Incident, histologically confirmed cases of RCC were
identified from hospital records in North Florida and
through the Florida Cancer Data System registry. All white
and African-American cases aged 20 years or older and
diagnosed between January 1, 2000 and December 31,
2004 were considered for inclusion. Cases were excluded
if their cancer was diagnosed in a transplant kidney, if
they were diagnosed with transitional cell tumors, or if
they did not reside in Florida or Georgia. Among 417 liv-
ing, eligible cases contacted, 304 (73%) participated in
the study. Fifteen additional cases were included from
urology clinics in North-Central Florida, four through
Emory University Hospital in Atlanta, Georgia, and 12


through the Malcom Randall VA Medical Center in
Gainesville, Florida, producing a total sample of 335
cases. The resulting sample was drawn from 22 counties in
North-Central Florida, two counties in South Florida, two
counties in the Florida Panhandle, two counties in South-
eastern Georgia, and Atlanta.

A sample of population controls was concurrently identi-
fied using random-digit dialing (RDD) [10], frequency-
matched to cases by age (+/- 5 years), gender and race.
Sampling frames were based on permutations of the tele-
phone numbers of cases, holding area code and three-
digit prefix constant, which allowed controls to be identi-
fied from the same cities as cases. During the first year of
the study, frequencies from Surveillance, Epidemiology,
and End Results (SEER) data [11] were used for matching
until an adequate case sample was acquired. Respondents
were eligible as controls if they met matching criteria and
reported no history of kidney cancer. Among 801 eligible
respondents contacted by telephone, 337 (42%) partici-
pated as controls.

Ethical approval was obtained from the institutional
review boards of the University of Florida (UF IRB-01)
and secondary study sites. Subjects who provided
informed consent to participate were interviewed in per-
son between August 2003 and December 2006 using a
structured questionnaire, minimizing the potential for
interviewer bias [12]. The questionnaire assessed medical,
occupational, and family histories, lifetime history of use
of medications, tobacco, coffee, tea, and artificial sweeten-
ers, and lifetime exposure to radiation, pesticides, and
environmental tobacco smoke. Dietary information was
collected using a Block food frequency questionnaire [13].
Body mass index (BMI) was calculated at time of interview
by measuring height in centimeters and weight in kilo-
grams (kg/m2).

Subjects were classified as "ever-smokers" of cigarettes if
they reported smoking at least 100 cigarettes during their
lifetime. Subjects were asked to indicate the number of
cigarettes they smoked per day separately for each of eight
age-decade groups. Discrete values from each group were
summed to produce a lifetime exposure value, using vali-
dated methods for the retrospective calculation of pack-
years (1 pack-year = 1 pack/day for one year) [14] and tak-
ing into account periods of temporary cessation. Ever-
smokers were asked whether they normally inhaled into
the chest or into the mouth when they smoked.

Exposure to ETS was assessed separately for home, work-
place, and public or private locations. For home exposure,
subjects were asked whether they had ever lived with
someone who smoked inside their home for at least one
year. For each home indicated, years of co-habitation and


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average number of hours per day of ETS exposure were
collected. Summary measures of home ETS exposure
duration and lifetime hours of exposure (years x hours)
were calculated by adding estimates for each home.

For workplace ETS exposure, subjects were asked whether
they had been exposed to others' cigarette smoke in the
workplace for at least one year, the number of years of
employment in such jobs, and the average number of
hours per day exposed. Additionally, subjects were asked
to indicate the average number of smokers within 10 feet
of them in the workplace.

Exposure to ETS in "cars, public transport, restaurants,
bars, or other public/private places" was also evaluated
(public ETS exposure). Subjects were considered exposed if
they reported exposure in these places for at least one
hour per week, during the time in their life when they fre-
quented such locations "most often". Frequency of expo-
sure was collected in hours per week and grouped into
three categories: (1) 1-2 hours; (2) 3-6 hours; or (3) 7 or
more hours. Because public ETS is common in bars and
restaurants, analyses were controlled for weekly alcohol
consumption in the past year. This variable was con-
structed from responses to questions on beer, wine, and
liquor, with one point assigned for each beverage the sub-
ject reported drinking at least once per week (score range:
0 3). An additional point was added for subjects report-
ing to have consumed more alcohol in the past than pres-
ently.

Statistical analyses were performed using SPSS 14.0 soft-
ware (SPSS Inc., Chicago). Comparisons of demographic
factors employed the Pearson z2 test for independence.
Relative risk statistics were estimated by the odds ratio
(OR) and 95% confidence interval (CI), using uncondi-
tional logistic regression. Adjusted models controlled for
age, gender, race, smoking, and BMI. Tests for trend
employed the Wald z2 statistic, computed for continuous
variables in adjusted models. Analyses of ETS exposure
were performed for never-smokers only.

Results
Cases and controls did not differ significantly with respect
to gender, race, or household income (Table 1). The dif-
ference in mean ages between cases (66 years) and con-
trols (62 years) was statistically significant (p = 0.001).
Cases were interviewed between 0.4 years and 6.3 years
following diagnosis, with a mean follow-up of 3.1 years.
Compared with healthy BMI (18.5 24.9), being obese
(BMI 30 39) was associated with an 80% increase in
RCC risk for both men (OR = 1.8; 95% CI: 0.9 3.6) and
women (OR = 1.8; 95% CI: 1.0 3.3). Based on these
findings, all multivariate analyses were controlled for
BMI, in addition to age, gender and race. Hypertension is
also considered an important risk factor in the epidemiol-


ogy of RCC [3], although no associations were found in
the present study an effect that was likely due to misclas-
sification of subjects who claimed to be hypertensive by
self-report, but were never formally diagnosed. Hyperten-
sion was therefore not included as a covariate in subse-
quent analyses.

A multivariate logistic regression model was used to calcu-
late odds ratios for lifetime smoking measured in years,
pack-years, inhalation and smoking cessation (Table 2).
RCC risk increased with increasing duration of smoking in
years (p = 0.055), although few odds ratios across decade-
intervals were significant. When compared with those
smoking for less than 20 years, those who smoked for 20
years or longer experienced a 60% increase in RCC risk.
Trends between RCC and direct smoking were stronger
when exposure was measured in pack-years (p = 0.014).
Those who smoked 20 or more pack-years experienced a
marginally significant 30% risk increase compared with
never-smokers. This association was greater when smok-
ers of 20 or more pack-years were compared with those
smoking less than 20 pack-years.

Among ever-smokers, those who reported inhaling expe-
rienced an 83% increase in risk, compared with those who
did not inhale. However, this association was attenuated
when pack-years were included in the model (OR = 1.59;
95% CI: 0.88 2.86), suggesting confounding by dose.
Among those who smoked 30 or more pack-years, 90%
reported inhaling, compared with 73% of those who
smoked less than 10 pack-years.

The strongest associations in this study were found for
smoking cessation. Among ex-smokers, a trend of decreas-
ing risk was observed across 10-year cessation intervals,
using as a reference group those who had quit 1-10 years
before interview. A 60% decrease in risk was observed for
those who had quit 11-20 years prior to interview.

Table 3 shows results for ETS exposure among never-
smokers. Exposure to home ETS significantly increased
risk for RCC, whether tested as years (p = 0.010) or life-
time hours of exposure (p = 0.008). Compared with those
reporting no home ETS exposure, those with greater than
20 years of exposure were more than twice as likely to
develop RCC. Likewise, those with 30,000 hours or more
of lifetime exposure a figure equivalent to 5 hours a day
for over 16 years were 2.4 times more likely to develop
RCC. Those exposed to ETS in the workplace for 1 20
years were twice as likely to develop RCC as those never
exposed. However, this represents the middle range of
workplace ETS exposure; at the higher range (greater than
20 years), no association was observed. No significant
trends were otherwise found between workplace or public
ETS exposure and RCC.


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Table I: Demographic characteristics of RCC cases and controls, Florida and Georgia


Age at interview
20 29 years
30 39 years
40 49 years
50 59 years
60 69 years
70 79 years
80 + years


Gender
Female
Male


Race
White
African-American

Education
Less than high school
High school diploma
Bachelor's or higher

Annual household income
Less than $ 10,000
$10,000 $14,999
$15,000 $19,999
$20,000 $24,999
$25,000 $34,999
$35,000 $49,999
$50,000 $74,999
$75,000 and higher
Not reported

Body mass index
18.5 -24.9
25.0 29.9
30.0 39.9
40.0 +


Table 4 presents results for combined home and work-
place ETS exposure, in hours. Results are shown for all
never-smokers combined, and stratified by public ETS
exposure (> 1 hour per week vs. < 1 hour per week). Those
in the 4th quartile of combined ETS exposure were 3 times
more likely to develop RCC than those in the 1st quartile
(trend p = 0.020). Among never-smokers who reported
public ETS exposure, those in the 4th quartile of combined
ETS exposure were approximately 4 times more likely to
develop RCC than those in the 1st quartile.

A stratified analysis by age was also performed to check
assumptions of the previous analysis which combined all
age groups. Time-dependent variables such as pack-years
and years of ETS exposure are expected to increase with
age. In order to assess the impact of this co-linearity,


descriptive statistics for time-dependent variables were
calculated, and models were fit, for separate age groups
(Tables 5 and 6). For all variables, those subjects younger
than 50 years old were consistently below mean exposure
values. Furthermore, only subjects between 50 and 80
years old had adequate observations of 20 or more pack-
years, and interpretation of pack-years associations
reported in this paper should therefore be limited to that
age group. With smoking variables and age both treated as
continuous, the correlation coefficient was of notable
magnitude only for smoking cessation (Spearman's =
0.388, p < 0.0001). Although this suggests potential con-
founding by age, the expected effect of confounding is
contrary to the observed trend. Risk of RCC is known to
increase with age, which would produce a trend of
increasing risk (or moderated protective effect) as years of



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Pearson z2

17.239









0.220


p-value

0.008









0.644


Cases (%)


1 (0.3%)
2 (0.6%)
25 (7.5%)
63 (18.8%)
108 (32.2%)
95 (28.4%)
41 (12.2%)


154 (46.0%)
181 (54.0%)


262 (78.2%)
73 (21.8%)


41 (12.3%)
184 (55.1%)
109 (32.6%)


19(5.9%)
19(5.9%)
19(5.9%)
41 (12.7%)
48(14.8%)
59(18.2%)
58(17.9%)
53 (16.4%)
8 (2.5%)


50(15.0%)
118 (35.3%)
135 (40.4%)
31 (9.3%)


Controls (%)


9 (2.7%)
11 (3.3%)
38(1 1.3%)
64(19.0%)
98(29.1%)
81 (24.0%)
36(10.7%)


161 (47.8%)
176 (52.2%)


266 (78.9%)
71 (21.1%)


28 (8.3%)
183 (54.3%)
126 (37.4%)


25 (7.5%)
20 (6.0%)
28 (8.4%)
24 (7.2%)
44 (13.3%)
54 (16.3%)
65(19.6%)
65(19.6%)
7(2.1%)


70(21.3%)
123 (37.4%)
11I (33.7%)
25 (7.6%)


0.052



3.668


0.85 I



0.160


8.998


0.342











0.094


6.384


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Table 2: Crude and adjusted odds ratios for renal cell carcinoma: cigarettes and cigarette smoking cessation


Cases
(%)


Controls
(%)


OR
(95% Cl)


AOR
(95% CI)a


X2
trendb


Lifetime cigarette smoking


Duration (years)
Never-smokers
I 10 years
II 20 years
21 30 years
31 40 years
41 50 years
51 + years
Total


131 (39%)
22 (7%)
29 (9%)
42(13%)
56(17%)
32(10%)
23 (7%)
335 (100%)


Dichotomous measure
< 20 years
20 + years


Dose + duration (pack-years)
Never-smokers
< 5 pack-years
5 to < 10 pack-years
10 to < 20 pack-years
20 or more pack-years
Total


Dichotomous measure
< 20 pack-years
20 or more pack-years


Smoking technique
Inhalation into mouth/throat only
Inhalation into chest/lungs
Total

Cigarette cessation (years)d
I 10 years
II 20 years
21 30 years
31 40 years
41 50 years
51 or more years
Total


134 (40%)
46(14%)
39(12%)
39(12%)
30 (9%)
29 (9%)
20 (6%)
337 (100%)


176 (52%) 216 (64%)
159 (48%) 121 (36%)


131 (39%)
29 (9%)
14(4%)
33 (10%)
128 (38%)
335 (100%)


134 (40%)
50(15%)
24 (7%)
33 (10%)
96 (29%)
337 (100%)


207(62%) 241 (71%)
128 (38%) 96 (29%)


29 (12%)
176 (88%)
205 (100%)


48 (29%)
36 (22%)
28 (17%)
28 (17%)
18 (i 1%)
7 (4%)
165 (100%)


41 (19%)
161 (81%)
202 (100%)


20(14%)
27(19%)
34 (24%)
30(21%)
18 (13%)
11 (8%)
140 (100%)


1.00 (ref.)
0.49 (0.28 0.86)
0.76 (0.44 1.30)
1.10 (0.67- 1.81)
1.91 (1.15 3.16)
1.13 (0.65 1.97)
1.18 (0.62 2.24)



1.00 (ref.)
1.60 (1.17- 2.19)


1.00 (ref.)
0.64 (0.38 1.06)
0.61 (0.30 1.22)
1.04 (0.61 1.78)
1.39 (0.97- 1.98)



1.00 (ref.)
1.53 (1.10 -2.14)


1.00 (ref.)
1.89 (1.07- 3.35)



1.00 (ref.)
0.56 (0.27- 1.14)
0.34 (0.17- 0.71)
0.39 (0.19- 0.81)
0.42 (0.18 0.96)
0.27 (0.09 0.78)


1.00 (ref.)
0.52 (0.29 0.93)
0.73 (0.42 1.28)
1.19 (0.71 1.99)
1.87 (1.12 3.13)
1.05 (0.60 1.84)
1.05 (0.54 2.04)



1.00 (ref.)
1.57(1.15 -2.15)


1.00 (ref.)
0.68 (0.40 1.15)
0.62 (0.31 1.27)
1.1 1(0.64 1.92)
1.35 (0.93 1.95)



1.00 (ref.)
1.48 (1.06 2.07)


1.00 (ref.)
1.83 (1.03 3.26)



1.00 (ref.)
0.39 (0.18 0.85)
0.24 (0.1 I 0.52)
0.28 (0.13 -0.61)
0.23 (0.09 0.58)
0.1 I (0.03 0.39)


a Adjusted for age, gender, race and BMI. b Reported only for continuous variables in adjusted models.
c Ever-smokers only. d Ex-smokers only.


cessation increase. The present findings show that risk
clearly decreases with increasing years of smoking cessa-
tion. Descriptive statistics for years of home and work-
place ETS exposure across age groups show little evidence
of notable co-linearity.

Table 6 presents stratified analyses of cigarette smoking
(in pack-years) and home ETS (in years) at ten-year age
intervals (Table 6). Results for subjects younger than 40
years old were excluded from this table because low sam-
ple size within these age strata precluded meaningful
results. Within each age group, risk of RCC increased con-


sistently with increasing levels of pack-years and years of
home ETS. Associations between RCC and home ETS were
particularly strong in the 70- to 79-year age group, with
greater than 20 years of exposure increasing risk by a mag-
nitude of six, compared with no exposure.

Discussion
This study observed a 30% RCC risk increase among
smokers of 20 or more pack-years compared with never-
smokers. This finding is consistent with those of previous
case-control studies [7,15-191, and conflicts with only two
[20,211 for which pack-years were reported. Cohort stud-



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p = 0.055


p = 0.014


p < 0.001


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Table 3: Crude and adjusted odds ratios for renal cell carcinoma: environmental tobacco smoke exposure among never-smokers


Cases
(%)


Home ETS exposure
Duration (years)
No exposure
I 20 years
> 20 years
Total


Lifetime hours
No exposure
I 29,999 hours
30,000 + hours
Total


Workplace ETS exposure
Duration (years)
No exposure
I 20 years
> 20 years
Total


Lifetime hours
No exposure
I 16,999 hours
17,000 + hours
Total


Smoker proximity
< 5 smokers within 10'c
> 5 smokers within 10'
Total

Public/private ETS exposured
< I hour per week
I 2 hours per week
3 6 hours per week
> 7 hours per week
Total


35 (27%)
38 (30%)
56 (43%)
129 (100%)


37 (29%)
41 (32%)
50 (39%)
128 (100%)



55 (43%)
48 (37%)
26 (20%)
129 (100%)


55 (43%)
38 (30%)
36 (28%)
129 (100%)


44 (60%)
29 (40%)
73 (100%)


42 (33%)
52(41%)
22 (17%)
12 (9%)
128 (100%)


Controls
(%)



43 (32%)
59 (44%)
32 (24%)
134 (100%)


44 (33%)
62 (46%)
28 (21%)
134 (100%)



73 (55%)
32 (24%)
29 (22%)
134 (100%)


73 (55%)
28 (21%)
33 (25%)
134 (100%)


43 (71%)
18(30%)
61 (100%)


54 (40%)
46 (34%)
16 (12%)
18 (13%)
134 (100%)


OR
(95% Cl)


1.00 (ref.)
0.79 (0.43 1.45)
2.15 (1.15 -4.01)



1.00 (ref.)
0.79 (0.44 1.42)
2.12 (1.12 -4.01)




1.00 (ref.)
1.99 (1.13 3.51)
1.19 (0.63 2.25)



1.00 (ref.)
1.80 (0.99 3.28)
1.45 (0.80 2.61)



1.00 (ref.)
1.57 (0.76 3.24)



1.00 (ref.)
1.45 (0.83 2.56)
1.77 (0.83 3.78)
0.86 (0.37- 1.97)


AOR
(95% CI)a


1.00 (ref.)
0.86 (0.46 1.60)
2.18 (1.14 -4.18)



1.00 (ref.)
0.83 (0.45 1.52)
2.37 (1.20 -4.69)




1.00 (ref.)
2.09 (1.17 3.75)
1.04 (0.54 2.01)



1.00 (ref.)
1.83 (0.99 3.37)
1.36 (0.74 2.49)



1.00 (ref.)
1.47 (0.70 3.08)



1.00 (ref.)
1.59 (0.88 2.87)
2.25 (0.99 5.09)
0.87 (0.37 -2.05)


a Adjusted for age, gender, race, and BMI. b Reported only for continuous variables in adjusted models.
c Assessed only for those reporting workplace ETS exposure. d Adjusted for age, gender, race, BMI, and weekly alcohol consumption.


ies have also reported positive associations between
smoking and kidney cancer incidence [22,23] or mortality
[24,25]. For smokers of 20 or more pack-years, we
observed a more significant risk increase when the refer-
ence group included both never-smokers and those smok-
ing less than 20 pack-years. The apparent protective effect
of light smoking is likely explained by the high propor-
tion of ex-smokers (90%) among those classified as light
smokers.

While the etiologic link between smoking and RCC is well
established, these results contribute to existing knowledge
using a refined measure that accounts for variations in
lifetime smoking patterns. Retrospective methods for cal-
culating pack-years that take into account temporary peri-


ods of cessation have been found moderately valid when
compared against prospective methods [14]. This study
modifies this method further by assessing smoking pat-
terns across discrete age intervals. Correspondence of
these estimates with those found in the literature lends
weight to the potential validity of home ETS measures
used in this study, which relied on the same measurement
principles. However, it should be noted that our methods
for assessing pack-years require further study for valida-
tion.

The protective effects of smoking cessation were particu-
larly strong in this study. These findings are more conclu-
sive than those of other studies evaluating RCC risk
among ex-smokers [6,15-20,26,27], although differing



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z2 trend



p = 0.010






p = 0.008


p = 0.740


p = 0.972






p = 0.370


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Table 4: Summary homework ETS exposure (lifetime hours) among never-smokers, by public ETS exposure


Cases
(%)


Home/work ETS exposure, quartilesb
It quartile: 22 (1
0 6,569 hours
2nd quartile: 30(2
6,570 24,454 hours
3rd quartile: 34 (2
24,455 67,707 hours
4th quartile: 42 (3
67,708 + hours
Total 128(1


Controls
(%)


41 (31%)

38 (28%)

32 (24%)

23 (17%)


7%)

.3%)

.7%)

3%)


OR
(95% Cl)


1.00 (ref.)

1.47 (0.73 2.98)

1.98 (0.98 4.02)

3.40 (1.65 7.03)


AOR
(95% Cl)


1.00 (ref.)

1.33 (0.65 2.72)

1.92 (0.94 3.94)

3.04 (1.44 6.42)


00%) 134 (100%)


Home/work ETS exposure, quartiles no public ETSc
Ist quartile: 15 (36%) 22(41%)
0 6,569 hours
2nd quartile: 11 (26%) 15 (28%)
6,570 24,454 hours
3rd quartile: 7 (17%) 12 (22%)
24,455 67,707 hours
4th quartile: 9 (21%) 5 (9%)
67,708 + hours
Total 42(100%) 54 (100%)

Home/work ETS exposure, quartiles -with public ETSc
It quartile: 7(8%) 19 (24%)
0 6,569 hours
2nd quartile: 19 (22%) 23 (29%)
6,570 24,454 hours
3rd quartile: 27 (31%) 20 (25%)
24,455 67,707 hours
4th quartile: 33 (38%) 18 (23%)
67,708 + hours
Total 86(100%) 80(100%)

a Reported only for continuous variables in adjusted model
bAdjusted for age, gender, race and BMI
cAdjusted for age, gender, race, BMI, and weekly alcohol consumption
reference categories preclude direct comparisons. Yuan et
al. (1998) found that, compared with current smokers,
those who had quit smoking for 10 or more years experi-
enced a 30% RCC risk reduction [28]. Parker et al. (2003)
reported a 50% reduction in risk among those who had
quit for 30 or more years, compared with current smokers
[27]. Our analysis was performed among ex-smokers
only, using as a reference those who had quit 1-10 years
prior to interview. This study had an average follow-up for
cases of three years, and it is likely that many cases who
were current smokers prior to diagnosis would have quit
by the time of interview. Analyses of cessation using cur-
rent smokers as a reference would therefore have resulted
in an artificially lower proportion of cases in the reference
group a potential bias that could underestimate the pro-
tective effect of cessation.

While this study found increased RCC risks among ever-
smokers who reported inhaling, these associations were
attenuated after controlling for pack-years. Mellemgaard


p = 0.214


1.00 (ref.)

1.08 (0.39 2.98)

0.86 (0.27 2.68)

2.64 (0.74 9.45)




1.00 (ref.)

2.24 (0.78 6.46)

3.66 (1.29 10.39)

4.98 (1.76 14.07)


1.00 (ref.)

1.05 (0.35 3.13)

0.80 (0.24 2.68)

2.32 (0.60 8.96)




1.00 (ref.)

1.91 (0.62 5.87)

3.53 (1.19- 10.47)

4.05 (1.35- 12.17)


p = 0.153


(1995) reported a similar confounding effect, in which
the association between inhalation and risk was likely
explained by the fact that heavier smokers tended to
inhale more frequently [17]. Other studies have reported
conflicting results on inhalation and RCC [6,16,28], par-
ticularly when inhalation patterns were evaluated across
"deep", "moderate" and "light" categories. A dichoto-
mous inhalation measure is probably sensitive enough to
detect potential effects.

This study is among the first to observe associations
between RCC and home ETS exposure among never-
smokers. We know of only two other case-control studies
to date that have evaluated associations between ETS and
RCC [6,7]. Both studies assessed self-reported home and
workplace ETS exposure in Canadian populations using
mailed questionnaires. Krieger et al. (1993) observed
non-significant risk increases for both non-smoking men
(OR = 1.6) and women (OR = 1.7) reporting greater than
8 hours of daily ETS exposure [6]. Hu et al. (2005)



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p = 0.020


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Table 5: Descriptive statistics for cigarette smoking and ETS exposure (home and workplace), by age-decadea,b


Cigarette duration
(yrs.)c


Mean
2.80
7.62
11.30
17.05
20.64
19.72
12.88

17.44


St. dev.
3.36
8.95
13.75
16.06
19.76
20.45
18.13


Cigarette pack-yearsd


Mean
0.61
4.18
8.36
18.09
20.68
21.08
11.69


St. dev.
0.92
5.75
13.36
22.33
27.45
27.74
25.56


17.49 25.33


Cigarette cessation
(yrs.)e


Mean
4.00
4.33
14.29
16.85
23.20
28.61
36.48

24.66


St. dev.

4.16
11.18
12.05
13.34
15.50
16.16


Home ETS yearsf Work ETS years


Mean
2.50
11.14
13.93
13.78
17.00
19.00
19.03


St. dev.
3.00
9.87
11.39
13.99
16.43
16.30
21.17


St. dev.
2.24
3.73
9.76
10.84
14.53
14.39
15.49


15.39 16.45 16.17 9.65 13.40


a Spearman's correlation coefficients reported for both variables as continuous.
b Cigarette duration and pack-years reported for full sample (N = 672); Cigarette cessation reported for ex-smokers only (N = 305); ETS statistics
reported for never-smokers only (N = 263).
cF = 5.163, p < 0.0001; Spearman's = 0.048, p = 0.215
d F = 4.668, p < 0.000 I1; Spearman's = 0.022, p = 0.564
e F = 10.822, p < 0.0001; Spearman's = 0.388, p < 0.0001
f F = 1.354, p = 0.234; Spearman's = 0.102, p = 0.121
gF = 1.699, p = 0.122; Spearman's = 0.029, p = 0.636


reported significant risk increases for 43 or more years of
combined home and workplace ETS exposure (compared
with those never exposed) among non-smoking men (OR
= 3.9) and women (OR = 1.8) [7]. The present study
reports a comparable OR of 3.04 for the highest quartile
of combined home and workplace ETS exposure.

The implausibility of ETS risk ratios that exceed risk ratios
for direct smoking both in this study and in the litera-
ture may be partly explained by the differing composi-
tion of reference groups. Analyses of smoking are
performed for the entire sample with never-smokers as the
reference group, including those exposed to ETS an
effect that may slightly increase the odds of being a case in
the reference group (from Table 2, odds: 131/134 = 0.98)
and thus dampen the estimated odds ratio. Conversely,
analyses of ETS exposure are performed on the subsample
of never-smokers, among whom the reference group has
no history of ETS exposure and lower odds of being a case
(from Table 5, odds: 35/43 = 0.81). In Table 2, substitu-
tion of the lower odds for the "purer" referent group (nei-
ther direct nor indirect smoke exposure) into the
calculation of an unadjusted OR for smoking greater than
20 years would increase the OR from 1.33 to 1.60. From
Table 3, the comparable unadjusted OR for home ETS
exposure of greater than 20 years is 2.15. Thus, home ETS
still appears to have a larger effect than direct smoking,
even after using the same reference group. A basic statisti-
cal explanation for this is that the ETS effect estimates are
based on much smaller samples and are highly variable;
the true ETS effects are probably smaller than reported
here. A fully satisfactory explanation for why ETS appears
to have a larger effect than direct smoking is lacking; a rea-
sonable hypothesis for future research is that the differ-


ences in effect estimates reflect the as-yet unclear role of
confounders such as dietary and other lifestyle factors.

Home ETS was assessed by both years of exposure, which
does not account for intensity, and lifetime hours of expo-
sure a computed variable that incorporates both dura-
tion and intensity resulting in different standards of
precision. The risk increases reported here are based on
variables assessed by interviewers trained in retrospective
data collection a method that typically provides higher
estimates of sensitivity and specificity [29]. However,
unlike ETS measurement based on shorter recall periods
[8,30], methods for measuring long-term, retrospective
ETS exposure have not been validated.

While this study reported associations between RCC and
home ETS, it remains unclear why similar associations
were not found for workplace or public ETS. It is possible
that potential associations were not detected due to meas-
urement error. While ETS exposure in the home was meas-
ured using separate estimates for each home in which the
subject lived with a smoker, workplace ETS was collected
as an overall estimate, and only frequency data were col-
lected for public ETS. Self-reported ETS measures in the
workplace may be problematic due to variations in room
volume, ventilation, and employee turnover [8,31]. Fur-
thermore, concentrations of both workplace and public
ETS vary by setting, with higher concentrations in indoor
locations and those with a greater number of smokers
(e.g., bars and restaurants). The public ETS measure for
the present study did not differentiate between exposure
in cars or public transportation (high concentration) and
exposure in outdoor locations, such as bus stops or restau-
rant patios (low concentration), resulting in low specifi-



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Age
(years)


20 -29
30-39
40-49
50 -59
60 -69
70 -79
> 80


Total


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Table 6: Adjusted odds ratios for renal cell carcinoma by age-decade: Cigarette smoking (pack-years) and home ETS (years)


Cigarette smoking (pack-years)a


Cases (%) Controls (%)


AOR
(95% CI)c


Home ETS (years)b

Cases (%) Controls (%)


1.00
0.48 (0.13 1.70)
1.26 (0.29 5.55)



1.00
0.69 (0.26 1.78)
1.61 (0.69 3.79)



1.00
0.57 (0.28 1.15)
0.84 (0.43 1.64)



1.00
1.06 (0.49 2.31)
1.32 (0.64 2.71)



1.00
0.90 (0.26 3.12)
2.18 (0.62 7.70)


5 (36%)
6 (43%)
3 (21%)
14 (100%)


5 (23%)
10(46%)
7 (32%)
22 (100%)


13 (33%)
10(25%)
17(43%)
40(100%)


6 (19%)
6 (19%)
20 (63%)
32(100%)


6 (30%)
6 (30%)
8 (40%)
20 (100%)


5 (28%)
8 (44%)
5 (28%)
18 (100%)


7 (30%)
13 (57%)
3 (13%)
23 (100%)


7 (25%)
14 (50%)
7 (25%)
28 (100%)


12(38%)
11 (34%)
9 (28%)
32(100%)


7 (32%)
7 (32%)
8 (36%)
22 (100%)


1.00
0.85 (0.15 -5.01)
0.83 (0.1 I -6.27)



1.00
0.66 (0.14 -3.1 1)
2.20 (0.30 15.94)



1.00
0.35 (0.08 1.49)
1.17 (0.28 -4.94)



1.00
1.17 (0.28 -4.97)
6.29 (1.50 26.29)



1.00
1.48 (0.24 -9.14)
1.43 (0.30 6.86)


a Cigarette smoking
Reference: never-smoker
Level I: _< 20 pack-years
Level 2: > 20 pack-years
b Home ETS
Reference: never exposed
Level I: < 20 years
Level 2: > 20 years
cAdjusted for gender, race, and BMI

city and possibly contributing to exposure observed among teachers born in the 1930s (78%). In
misclassification. comparison, among controls in the present study aged 60
69 years or 70 79 years, lifetime home ETS prevalence
Although these results suggest that home ETS is impli- was 75% and 62%, respectively. The home ETS estimates
cated in the etiology of RCC, a number of limitations collected from the control sample may therefore be
must be acknowledged. The low response rate among con- slightly lower than that found in the general population,
trols (42%) suggests that selection biases may have been suggesting that their corresponding odds ratios (e.g., 2.18
present, with controls choosing to participate having for greater than 20 years of exposure) overestimate the
healthier lifestyle patterns than those who refuse. This true measure of association. While the magnitude of this
potential bias would result in lower exposure rates within study's home ETS estimates may be in question, one may
the control sample compared to the general population, still conclude from these findings that long-term ETS
producing overestimated measures of association [121. In exposure in the home is a likely risk factor for RCC. Low
a study of ETS exposures among female teachers in Cali- response among controls is a significant limitation in the
fornia, the prevalence of lifetime ETS exposure in the present study, but it should be noted that our response
home ranged from 45% to 78%, depending on the rate reflects an observed trend in epidemiologic studies
teacher's birth decade [321. The highest prevalence was over the past thirty years [12,33,341, with participation


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AOR
(95% CI)c


40 49 years
Reference
Level I
Level 2
Total

50 59 years
Reference
Level I
Level 2
Total

60 69 years
Reference
Level I
Level 2
Total

70 79 years
Reference
Level I
Level 2
Total

> 80 years
Reference
Level I
Level 2
Total


14 (56%)
6 (24%)
5 (20%)
25 (100%)


22 (35%)
12 (19%)
29 (46%)
63 (100%)


40 (37%)
26 (24%)
42 (39%)
108 (100%)


32 (34%)
23 (24%)
40 (42%)
95 (100%)


21 (51%)
9 (22%)
11 (27%)
41 (100%)


18(47%)
14 (37%)
6 (16%)
38(100%)


23 (36%)
21 (33%)
20(31%)
64 (100%)


29 (30%)
33 (34%)
36 (37%)
98 (100%)


32 (40%)
21 (26%)
28 (35%)
81 (100%)


22(61%)
9 (25%)
5 (14%)
36(100%)


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rates for population-based case-control studies declining
nearly 2% per year [33].

The age discrepancy between cases and controls occurred
from obtaining initial matching frequencies from SEER
data, which are based on cancer incidence reporting at the
national level. Because lifetime smoking and ETS variables
are time-dependent, the potential of co-linearity or con-
founding with age was a concern. Univariate descriptive
statistics on selected tobacco variables showed expected
increases in exposure levels with age, but little evidence of
confounding (with the exception of smoking cessation)
(Tables 5 and 6). Trends in the association between RCC
and increasing levels of pack-years or years of home ETS did
not differ substantially with age (Table 6).

Among cases, the average follow-up was three years, lead-
ing to potential survivor bias in which excluded deceased
cases may have had different exposure rates than those
included in the sample. However, with regard to smoking,
higher rates of exposure are more likely among deceased
cases, making findings more conservative. This follow-up
duration also introduces the potential for recall bias, with
cases interviewed shortly after diagnosis having more
accurate recall than those interviewed distant to diagnosis.
Estimates calculated using a subset of 92 cases interviewed
within two years of diagnosis were not appreciably differ-
ent from those calculated using the full case sample, sug-
gesting that inclusion of cases with longer follow-up did
not contribute to differential recall (results not shown).

Lastly, the cases in this study represent all histologic sub-
types of RCC, of which clear cell RCC is the most common
(85% to 90% of all renal tumors) [35]. Research has
shown that the different RCC subtypes produce varied
prognosis and outcomes in patients, and are morpholog-
ically and genetically distinct [36]. It is likely that the RCC
subtypes are also etiologically distinct, and inclusion of all
subtypes in a case-control study may affect the validity of
measures of association for the risk factors in question.

Conclusion
The findings from this study correspond with those of
prior studies that have reported associations between cig-
arette smoking and RCC and protective effects for smok-
ing cessation. Our results show that ETS exposure in the
home may act as an independent risk factor for RCC.
While the association is biologically plausible, additional
research is needed to validate these findings. More sensi-
tive self-report measures of ETS exposure are needed
which assess exposure by location, duration, and inten-
sity.

Abbreviations
RCC: renal cell cancer; ETS: environmental tobacco
smoke; OR: odds ratio; CI: confidence interval; RDD: ran-


dom-digit dialing; SEER: Surveillance, Epidemiology and
End Results; BMI: body mass index

Competing interests
The authors declare that they have no competing interests.

Authors' contributions
RPT participated in coordination of the study, collection
of data, statistical analysis, and drafted the manuscript.
SMDG participated in collection of data, assessment of
dietary factors, and review of the manuscript. DB con-
ducted and guided statistical analysis for the study and
reviewed the manuscript. TS provided medical consulting
for all aspects of the study. NRA conceived of the study
and participated in its design and coordination.

Acknowledgements
This research was supported by an American Cancer Society Research
Scholar Grant, TURSG-02-068-0 I-PBP, Dr. N.R. Asal, Principal Investiga-
tor.

References
I. Ries LAG, Melbert D, Krapcho M, Stinchcomb DG, Howlader N,
Horner MJ, Mariotto A, Miller BA, Feuer EJ, Altekruse SF, Lewis DR,
Clegg L, Eisner MP, Reichman M, Edwards BK, eds: SEER Cancer Sta-
tistics Review 1975-2005 [http://seer.cancer.gov/csr/1975 2005/].
Bethesda, MD: National Cancer Institute
2. American Cancer Society (ACS): Cancer Facts and Figures 2008
Atlanta, GA: American Cancer Society; 2008.
3. Lipworth L, Tarone RE, McLaughlin JK: The epidemiology of renal
cell carcinoma. j Urol 2006, 176:2353-2358.
4. HuntJD, Hel OL van der, McMillan GP, Boffetta P, Brennan P: Renal
cell carcinoma in relation to cigarette smoking: Meta-analy-
sis of 24 studies. Intj Cancer 2005, 114:101-108.
5. World Health Organization (WHO): Tobacco Smoke and Involuntary
Smoking, IARC Monographs Vo. 83 [http://monographs.iarc.fr/].
6. Kreiger N, Marrett LD, Dodds L, Hilditch S, Darlington GA: Risk fac-
tors for renal cell carcinoma: results of a population-based
case-control study. Cancer Causes Control 1993, 4:101- 110.
7. Hu J, Ugnat A-M: Active and passive smoking and risk of renal
cell carcinoma in Canada. Eurj Cancer 2005, 4 1:770-778.
8. U.S. Department of Health and Human Services (US DHHS): The
Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report
of the Surgeon General Rockville, MD: Public Health Service, Office of
the Surgeon General; 2006.
9. Sander DP, Everson RB, Wilcox AJ: Passive Smoking in Adult-
hood and Cancer Risk. Am J Epidemiol 1985, 121:37-48.
10. WaksbergJ: Sampling Methods for Random Digit Dialing. jAm
Stat Assoc 1978, 73:40-46.
I I. Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Mar-
iotto A, Fay MP, Feuer EJ, Edwards BK, eds: SEER Cancer Statistics
Review, 1975-2000 2003 [http://seer.cancer.gov/csr/1975 2000].
Bethesda, MD: National Cancer Institute
12. Austin H, Hill HA, Flanders D, Greenberg RS: Limitations in the
Application of Case-Control Methodology. Epidemiol Rev 1994,
16:65-76.
13. Block G, Woods M, Potosky A, Clifford C: Validation of a Self-
Administered Diet History Questionnaire Using Multiple
Diet Records. j Clin Epidemiol 1990, 43:1327-1335.
14. Bernaards CM, TwiskJWR, Snel J, Mechelen WV, Kemper HCG: Is
calculating pack-years retrospectively a valid method to esti-
mate life-time tobacco smoking? A comparison between
prospectively calculated pack-years and retrospectively cal-
culated pack-years. Addiction 2001, 96:1653-1662.
15. McLaughlin JK, Mandel JS, Blot WJ, Schuman LM, Mehl ES, Fraumeni
JF Jr: A population-based case-control study of renal cell car-
cinoma. j Natl Cancer Inst 1984, 72:275-284.



Page 10 of 11
(page number not for citation purposes)


BMC Cancer 2008, 8:387








http://www.biomedcentral.com/1471-2407/8/387


16. McCredie M, Stewart JH: Risk factors for kidney cancer in New
South Wales- I. Cigarette smoking. Eur J Cancer 1992,
28A:2050-2054.
17. Mellemgaard A, Engholm G, McLaughlin JK, Olsen JH: Risk factors
for renal cell carcinoma in Denmark. I. Role of socioeco-
nomic status, tobacco use, beverages, and family history.
Cancer Causes Control 1994, 5:105-I 13.
18. McLaughlin JK, Lindblad P, Mellemgaard A, McCredie M, Mandel JS,
Schlehofer B, Pommer W, Adami HO: International renal-cell
cancer study. I. Tobacco use. IntJ Cancer 1995, 60:194-198.
19. Muscat JE, Hoffmann D, Wynder EL: The epidemiology of renal
cell carcinoma. Cancer 1995, 75:2552-2557.
20. Goodman MT, Morgenstern H, Wynder EL: A case-control study
of factors affecting the development of renal cell cancer. Am
J Epidemiol 1986, 124:926-941.
21. Schlehofer B, Heuer C, Blettner M, Niehoff D, WahrendorfJ: Occu-
pation, smoking and demographic factors, and renal cell car-
cinoma in Germany. IntJ Epidemiol 1995, 24:51-57.
22. McLaughlin JK, Hrubec Z, Heineman EF, Blot WJ, Fraumeni JF Jr:
Renal cancer and cigarette smoking in a 26-year followup of
U.S. veterans. Public Health Rep 1990, 105:535-537.
23. Flaherty K, Fuchs CS, Colditz GA, Stampfer MJ, Speizer FE, Willett
WC, Curhan GC: A prospective study of body mass index,
hypertension, and smoking and the risk of renal cell carci-
noma (US). Cancer Causes Control 2005, 16:1099-1106.
24. Weir J, Dunn JE Jr: Smoking and Mortality: A Prospective
Study. Cancer 1969, 25:105-1 I I.
25. Coughlin SS, Neaton JD, Randall B, Sengupta A: Predictors of mor-
tality from kidney cancer in 332,547 men screened for the
Multiple Risk Factor Intervention Trial. Cancer 1997,
79:2171-2177.
26. La Vecchia C, Negri E, D'Avanzo B, Franceschi S: Smoking and
Renal Cell Carcinoma. Cancer Res 1990, 50:5231-5233.
27. Parker AS, Cerhan JR, Janney CA, Lynch CF, Cantor KP: Smoking
cessation and renal cell carcinoma. Ann Epidemiol 2003,
13:245-251.
28. Yuan J-M, Castelao JE, Gago-Dominguez M, Yu MC, Ross RK:
Tobacco Use in Relation to Renal Cell Carcinoma. Cancer Epi-
demiol Biomarkers Prev 1998, 7:429-433.
29. Woodward A, AI-Delaimy W: Measures of Exposure to Environ-
mental Tobacco Smoke. Ann NY Acad Sci 1999, 895:156-172.
30. Eisner MD, Katz PP, Yelin EH, Hammond SK, Blanc PD: Measure-
ment of Environmental Tobacco Smoke Exposure among
Adults with Asthma. Environ Health Perspect 2001, 109:809-814.
31. Willemsen MC, Brug J, Uges DRA, Vos de Wael ML: Validity and
Reliability of Self-Reported Exposure to Environmental
Tobacco Smoke in Work Offices. j Occup Environ Med 1997,
39:111 I 1114.
32. Reynolds P, Goldberg DE, Hurley S, The California Teachers Study
Steering Committee: Prevalence and Patterns of Environmen-
tal Tobacco Smoke Exposures Among California Teachers.
AmJ Health Promot 2004, 18(5):358-365.
33. Morton LM, Cahill J, Hartge P: Reporting Participation in Epide-
miologic Studies: A Survey of Practice. Am J Epidemiol 2005,
163:197-203.
34. Bunin GR, Spector LG, Olshan AF, Robison LL, Roesler M, Gruffer-
man S, Shu XO, Ross JA: Secular Trends in Response Rates for
Controls Selected by Random Digit Dialing in Childhood
Cancer Studies: A Report from the Children's Oncology
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