Association Between Smoking and
Primary Malignant Brain Tumors：
A Population-Based Case-Control Study in China
Smoking and brain tumors
Prof. Jingmei Jiang
Chinese Academy of Medical Sciences
& Peking Union Medical College, Beijing, China
Abstract code: 16517
Disclosure of Interest: None Declared
www.worldcancercongress.org
Brain Tumors in China
l 
l 
2.3% of all malignant tumors in China now
< 13% of 5-year survival rate for Adult Primary
Malignant Brain Tumors (PMBTs) according current
China Guideline
l 
Mortality rate of 194% in 2008 vs. 1970s and 101%
vs. 1990s
Jingmei Jiang
Duan, et al. China Cancer 2012
Melbourne 04 Dec 2014
2
Risk factors of PMBTs
Established
–  Lonizing radiation exposure
–  Unmodifiable factors such as sex, age, race, and
gene
Jingmei Jiang
Ostrom, et al. Curr Neurol Neurosci Rep 2011
Melbourne 04 Dec 2014 3
Population-based studies
l 
No significantly association between
smoking and BT
–  7 cohort studies
–  11 case-control studies
–  1 meta
Jingmei Jiang
Mandelzweig, et al. Cancer Causes Control 2009
Braganza, et al. Br J Cancer 2014
Melbourne 04 Dec 2014 4
STUDY AIM
To explore whether there was evidence of an
association between cigarette smoking and
deaths due to PMBTs
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STUDY DESIGN
l  Case-spouse
control study
design was raised by Chinese
epidemiologists Boqi Liu et al.
in 1991. The design was
incorporated into a nationwide
retrospective mortality survey
in China from 1989 to 1991.
Jingmei Jiang
Melbourne 04 Dec 2014
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STUDY DESIGN
l  In
1989-1991, a nationwide retrospective mortality survey was
conducted in China ,which involved 103 study areas and approximately
1,000,000 adult deaths from all causes during the years 1986-1988.
l  24
major cities which were chosen
to represent a wide geographical
spread
l  79
rural counties were selected
through stratified random sampling
among the 2,000 counties
l  Base
Jingmei Jiang
population including 67 million
7
Melbourne 04 Dec 2014
populations
STUDY DESIGN
l 
Within the study base, all deceased aged 35 or over were identified.
For those who died of causes related to smoking were taken as
cases, whereas surviving spouses of those who died from any
conditions during the same year were taken as controls. Exposure
information for both cases and controls was provided by living
spouses.
Jingmei Jiang
Melbourne 04 Dec 2014
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STUDY DESIGN
l 
The theoretical thinking of selecting controls
l 
l 
The distribution of all causes of deaths in the base
population is approximately at random, so is the spouse
population.
Assumptions in selection of controls
l  Individuals in the control group had smoking habits that
were similar to those of the study base.
l  There is no significant relationship in tobacco use
between couples
Jingmei Jiang
Melbourne 04 Dec 2014
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Case and Control in This Study
Cases defined as underlying
cause of PMBT deaths (ICD-9
code 191.0–191.9)
l 
All-cause deaths
1 136 336
`
Surviving
spouses
312 417
Controls defined as sex and
age-matched surviving spouses
of all-cause deaths.
l 
Excluded with missing data
or other malignant tumors
1:2
sampling
l 
Jingmei Jiang
PBMTs
4556
Controls
9112
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RESULTS
Population characteristics
l 
57.1% vs 42.9% for men and women
l 
82.1% vs 17.9% for urban and rural areas
l 
41.3% vs 39.2% for the prevalence of smoking in the
case and control group
l 
37.4% pathology-based diagnosis
Jingmei Jiang
Melbourne 04 Dec 2014 11
RESULTS
ü  The risk from smoking increased with age
30~39
40~49
50~59
60~69
70~
1.6
1.4
1.2
OR
1
0.8
0.6
0.4
0.2
0
Men
Women
Adjusted for age and urban or rural residence
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Melbourne 04 Dec 2014 12
RESULTS
35
32.4
29.2
30
ü  A much larger AFs
25
%
20
and PAFs among
15
individuals aged ≥
10
50 years
5
0
AF
Urban men
PAF
Urban women
Rural men
Rural women
OR (95%CI): 1.23 (1.09–1.39) 1.21 (1.02–1.44) 1.50 (1.11–2.02) 1.37 (0.82–2.30)
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Melbourne 04 Dec 2014 13
Dose-response relationship
l 
The risk increased with years of smoking
−  Consistent in pathology-based comparison
1.4
OR
1.24*
1.23*
1.2
*P for trend < 0.05
1
0.8
Non-smoker
0.6
<20
0.4
20~29
0.2
0
Jingmei Jiang
≥30
Men
Women
Melbourne 04 Dec 2014 14
Dose-response relationship
l 
The risk increased with cigarettes smoked daily
−  Consistent in pathology-based comparison
2
OR
1.71*
* P for trend < 0.05
1.5
1.24*
1
Non-smoker
<10
0.5
10~19
≥20
0
Jingmei Jiang
Men
Women
Melbourne 04 Dec 2014 15
Dose-response relationship
l  Synergistic
effects of years of smoking and
number of cigarettes smoked daily
Men
Women
1.50*
2.04*
2
1.5
1
≥ 30
20～ 29
<20
0.5
Non-smokers
Nonsmokers
<10
10～ 19
Cigarettes smoked daily
≥ 20
Years of
smoking
Adjusted ORs
Adjusted ORs
2.5
2
1.5
≥ 30
20～ 29
1
<20
0.5
Non-sm okers
Nonsm okers
<10
10～ 19
≥ 20
Years of
smoking
Cigarettes smoked daily
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Melbourne 04 Dec 2014
DISCUSSION
l 
The first study that indicates a positive association
of cigarette smoking with PMBTs among both men
and women worldwide.
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Melbourne 04 Dec 2014 17
DISCUSSION
In terms of risk factors of PMBTs, updated evidence
showed that, at the cerebrovascular level and
specifically at the blood-brain barrier, cigarette
smoking could severely impair endothelial function by
directly affecting endothelial tight junctions and the
ionic homeostasis across the endothelium. More
recently, an effect of nicotine on cellular proliferation,
migration, signaling, and radiation sensitivity, by
activating epidermal growth factor receptor and protein
kinase B, has been shown in.
l 
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Melbourne 04 Dec 2014 18
DISCUSSION
According to the pathophysiological and epidemiological evidence above , we hypothesized that
carcinogens in cigarette smoke may act to initiate
tumors in the brain, with an induction period of at least
30 years, similar to other malignant tumors. The
duration and dose of exposure to tobacco were highly
associated with PMBT deaths regardless of sex, age,
and urban or rural residence.
l 
Jingmei Jiang
Melbourne 04 Dec 2014 19
Discussion
l  A
key strength of this study is that it was a highquality, national-level, population-based case-control
study. A random sample of living spouses was
selected as controls using a computer-based
standardized algorithm. This approach was designed
to ensure that the sample of control spouses would
have similar smoking habits as those in the base
population, so that differences between the recorded
proportion of smokers in the case and control groups
could be used to calculate unbiased
Jingmei Jiang
Melbourne 04 Dec 2014
DISCUSSION
A limitation of this study lies in the multiple types of
PMBTs, which are not distinguishable under ICD
coding, but glioma accounts for the overwhelming
majority of PMBTs defined.
l 
l  This
study could not exclude recall bias and the
measurement error from surviving spouses and
survival bias from behavior change of patients after
diagnosis of PMBTs such as quitting smoking, which
might attenuate the association between smoking and
PMBTs.
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Melbourne 04 Dec 2014 21
Authors of this manuscript
Lei Hou, M.D; Jingmei Jiang, Prof.; Boqi Liu, Prof.;
Philip C. Nasca, Prof.; Yanping Wu, Prof.; Xiaonong
Zou, Prof.; Wei Han, Ph.D; Fang Xue, Ph.D; Yuanli
Chen, Research Assistant; Biao Zhang, M.Sc.; Haiyu
Pang, M.D.; Yuyan Wang, B.Sc; Zixing Wang, B.Sc;
Junyao Li, Prof.
Jingmei Jiang
Melbourne 04 Dec 2014 22
Contribution in this Project
"   We thank Cancer Research UK, the UK Medical Research
Council, the US National Institutes of Health, the Chinese
Ministry of Health, and the Chinese Academy of Medical
Sciences who supported the original survey;
"   We thank former minister Chen Min Zhang for his
encouragement, and cooperation of local governments;
"   We thank Professor Richard Peto, who gave us great support
for the project;
"   The thousands of doctors, nurses, and other field workers
who conducted the surveys, and the million interviewees are
great acknowledgments.
Jingmei Jiang
Melbourne 04 Dec 2014 23
Contribution in this paper
l 
This work, including analysis, decision to publish,
and preparation of the manuscript, has been
supported by a UICC International Cancer
Technology Transfer Fellowship under Contract
NO ICR/13/073 / 2013 UICC
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