Cigarette smoking and lung cancer – Risk estimates for the

Cigarette smoking and lung cancer – Risk estimates for the

Cigarette smoking and lung cancer –
Risk estimates for the major histological types
from a pooled analysis of case-control studies
Benjamin Kendzia1, Beate Pesch1, Per Gustavsson2, Karl-Heinz Jöckel3, Georg Johnen1, Hermann Pohlabeln4, Ann Olsson2,5, Wolfgang Ahrens4, Isabelle Mercedes Gross1, Irene Brüske6, Heinz-Erich Wichmann6, Franco Merletti7,
Dario Mirabelli7, Lorenzo Richiardi7, David Zaridze8, Adrian Cassidy9, Neonila Szeszenia-Dabrowska10, Peter Rudnai11, Jolanta Lissowska12, Isabelle Stücker13, Eleonora Fabianova14, Rodica Stanesan Dunitra15, Vladimir Bencko16,
Lenka Foretova17, Vladimir Janout18, Charles M. Rudin19, Jack Siemiatycki20, Javier Pintos20, Maria Teresa Landi21, Neil Caporaso21, Paul Brennan5, Paolo Boffetta22,23, Kurt Straif5, Thomas Brüning1
1
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of Ruhr-Universität Bochum (IPA), Bochum, Germany, 2 The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 3 Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Germany,
Bremen Institute for Prevention Research and Social Medicine, University of Bremen, Germany, 5 International Agency for Research on Cancer, Lyon, France, 6 Institut für Epidemiologie, Helmholtz-Zentrum München, Germany, 7 Cancer Epidemiology Unit, CPO-Piemonte and University of Turin, Italy, 8 Russian Cancer Research Centre, Moscow, Russia,
9
Roy Castle Lung Cancer Research Programme, Cancer Research Centre, University of Liverpool, UK, 10 The Nofer Institute of Occupational Medicine, Lodz, Poland , 11 National Institute of Environment Health, Budapest, Hungary, 12 The M Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland , 13 INSERM U 754 - IFR69, Villejuif, France,
14
Regional Authority of Public Health, Banska Bystrica, Slovakia, 15 National Institute of Public Health, Bucharest, Romania , 16 Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, 17 Masaryk Memorial Cancer Institute, Brno, Czech Republic, 18 Palacky University, Faculty of Medicine, Olomouc, Czech Republic,
19
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA, 20 Research Centre of University of Montreal Hospital Centre, University of Montreal, Canada, 21 National Cancer Institute, Bethesda, USA, 22 The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, USA, 23 The International Prevention Research Institute, Lyon, France
4
The SYNERGY project represents a
pooling of data from lung cancer
studies from Europe and Canada
where the primary objective is to
study joint effects of exposure to
occupational
carcinogens
and
smoking. Here we analyzed the lung
cancer risks of smoking in 13,169
cases and 16,010 controls.
Odds ratios (ORs) and 95% confidence intervals (CI) were estimated
for lung cancer and its major histological subtypes with logistic regression, conditional on study center and
adjusted for age. The reference group
comprised never smokers of any type
of tobacco but included occasional
smokers. Regular smoking of
cigarettes was defined as more than
one pack-year (py).
Acknowledgement
This study is supported by the German
Social Accident Insurance, grant FP 271.
Smoking status
Squamous cell cancer
Small cell lung cancer
Adenocarcinoma
P-valuea
N
Median (IQR)
N
Median (IQR)
N
Median (IQR)
N
Median (IQR)
10653
64 (57-69)
4699
64 (58-69)
1733
62 (56-68)
2348
64 (57-69)
<0.001
Never smokers
218
62 (55-70)
51
65 (57-73)
22
61 (51-70)
99
61 (54-68)
0.032
Former smokers
3496
67 (62-71)
1585
67 (62-71)
460
65 (60-70)
862
67 (61-71)
<0.001
Current smokers
6784
62 (55-68)
3038
62 (56-68)
1249
61 (54-67)
1398
62 (55-68)
<0.001
Total
P-valuea
Total
<0.001
2516
<0.001
63 (55-69)
561
<0.001
65 (57-70)
435
61 (53-68)
1007
62 (54-69)
<0.001
604
65 (58-71)
96
67 (58-72)
50
65 (58-71)
343
65 (59-71)
0.707
Former smokers
485
66 (58-71)
124
68 (61-71)
60
68 (61-71)
208
63 (55-71)
0.016
Current smokers
1423
60 (52-67)
343
64 (56-69)
331
58 (51-64)
462
59 (51-66)
<0.001
<0.001
<0.001
<0.001
<0.001
Abbreviation: IQR, interquartile range of the age distribution
a P-values of Kruskal-Wallis test of age differences between subtypes or smoking categories
Never and current smokers were presented with an earlier age than former smokers. A young age at
diagnosis was observed for female active smokers with SCLC or AdCa. Among never smokers, women
had a higher age at diagnosis than men.
Table 2: Lung cancer risk by smoking status
All histologies
Smoking status
Controls
Never smokers
2883
Squamous cell cancer
Small cell lung cancer
Adenocarcinoma
Cases
OR (95% CI)
Cases
OR (95% CI)
Cases
OR (95% CI)
Cases
OR (95% CI)
218
1.0
51
1.0
22
1.0
99
1.0
Former smokers
of cigarettes
5647
3496
Current smokers
of cigarettes
3829
6784 23.6 (20.4-27.2) 3038 45.6 (34.3-60.6)
7.5 (6.5-8.7)
1585
14.7 (11.0-19.6)
200
Squamous cell cancer
Small cell lung cancer
Adenocarcinoma
100
Squamous cell cancer
Small cell lung cancer
Adenocarcinoma
100
<0.001
Never smokers
P-valuea
200
Odds ratio
All histologies
observed an OR for
lung cancer of 7.5 (95%
CI 6.5-8.7) in men and 2.8
(95% CI 2.4-3.3) in women.
Similarly to active male
smokers, the risk estimates
for SqCC and SCLC were
higher than for AdCa.
460
10.1 (6.5-15.5)
862
4.2 (3.4-5.2)
1249
45.7 (29.9-70.0)
1398
10.8 (8.7-13.3)
Exclusively any other
type of tobacco
399
153
5.9 (4.6-7.4)
73
12.6 (8.6-18.4)
29
9.6 (5.4-17.0)
25
2.0 (1.3-3.2)
Never smokers
1902
604
1.0
96
1.0
50
1.0
343
1.0
Former smokers
of cigarettes
657
485
2.8 (2.4-3.3)
124
4.9 (3.7-6.6)
60
4.2 (2.8-6.2)
208
2.0 (1.6-2.4)
Current smokers
of cigarettes
691
1423
7.8 (6.8-9.0)
343
13.6 (10.5-17.7)
331
21.7 (15.5-30.1)
462
4.2 (3.5-5.0)
Overall, 218 male and 604 female cases reported that they never smoked more than one py. In never
smokers, AdCa was the prevailing subtype. SqCC was the leading histological type in male active or former
smokers but AdCa was the leading subtype in women. Current smoking of cigarettes was associated
with an OR for lung cancer of 23.6 (95% CI 20.4-27.2) in men and 7.8 (95% CI 6.8-9.0) in women. Higher
risk estimates in current smokers were observed for SqCC and SCLC than for AdCa. In ex-smokers, we
We found a significant trend
with increasing dose for all
subtypes and metrics of
exposure especiallyforSqCC
and SCLC. Here we present
the results for pack-years
in
current
smokers
(Figure 1). ORs for heavy
male smokers (> 60 py)
rised up to 47.7 (95% CI
38.5-59.0) with risks up
to about 100 for SqCC and
SCLC. Overall, women were
presented with about half
of the risk estimates than in
men.
1
1
>1-<20 20-<30 30-<40 40-<50 50-<60
>60
>1-<20 20-<30 30-<40 40-<50 50-<60
Pack-years
>60
Pack-years
Figure 1: Risk of lung cancer by cumulative exposure to tobacco
smoke
50
50
≥ 20 cig/day
< 20 cig/day
≥ 20 cig/day
< 20 cig/day
40
40
Odds ratio
METHODS
Table 1: Age at diagnosis of lung cancer by smoking status
Odds ratio
Lung cancer is a complex set of
molecularly
distinct
diseases.
Smoking is a risk factor for all forms
of lung cancer. Among active
smokers, squamous cell carcinoma
(SqCC) is the predominant subtype.
Smoking is also closely associated
with the development of small cell
lung carcinoma (SCLC). In never
smokers, adenocarcinoma (AdCa) is
the most common subtype.
We analyzed the lung cancer risks
of smoking with a large dataset of
pooled studies and explored the risk
estimates by histological subtype.
RESULTS
Odds ratio
AIMS
30
20
10
30
20
10
1
1
Current 2-5
smokers
6-10 11-15 16-25 26-35 >35
Current 2-5
smokers
6-10 11-15 16-25 26-35 >35
Time since cessation [years]
Time since cessation [years]
The risk reduction following
smoking cessation was Figure 2: Risk of lung cancer by time since cessation
assessed in relation to
never smokers (Figure 2). Former male smokers did not reverse to baseline level even when
quitting long-term. Also female smokers (> 20 cig/day) did not fully return to baseline. Cessation of
2-5 years already reduced the risk.
CONCLUSIONS
We found a younger age at diagnosis of lung cancer in never and active smokers than in former
smokers. Quitting of smoking reduced the risk already after few years but heavy smokers did
not fully return to baseline. Smoking was associated with stronger risks for SqCC and SCLC
than for AdCa.