1. Indoor Air Pollution, Environmental Tobacco Smoking, and Lung Cancer
The 5th International Conference on Environmental and Occupational Medicine
Dujiangyan, Chengdu, Sichuan, P.R. China
April 7-10, 2010
Indoor Air Pollution, Environmental Tobacco Smoking, and Lung Cancer
Zuo-Feng Zhang, MD, PhD
Professor, Department of Epidemiology
UCLA School of Public Health
UCLA Center for Environmental Genomics

2. 2 2

4. Source: Peto J, 2001 4

5. Age Standardized Incidence Rates (/100,000)US
China
World
Site
Males
Females
Stomach
7.2
3.3
41.4
19.2
22.0
10.3
Lung
61.9
36.1
42.4
19.0
35.5
12.1
Liver
5.5
2.0
37.9
14.2
15.7
5.8
Esophagus
4.9
1.3
27.4
12.0
11.5
4.7
Colon/Rectum
44.6
33.1
13.6
9.2
20.1
14.6
Breast ─
101.1
18.7
37.5
Leukemia
11.2
7.4
5.7
4.1
5.9
Pancreas
8.3
6.3
3.9
2.6
4.6
Cervix
7.7
6.8
16.2
Brain
6.5
4.5
2.8
3.7
Prostate
124.8
1.6
25.3
Source: GLOBOCAN 2002 5 5

6. Age-standardized Incidence Rates For Lung Cancer
Source: Figure 5: Parkin DM, et al. CA Cancer J Clin [2005]; 55:

7. Risk Factors for Lung Cancer
Tobacco smoking
Second hand smoking (passive smoking)
Asbestos
Radon exposure
Occupational exposures
Air pollution
Other radiation
Recurring inflammation
Family history of cancer
Insufficient diet and poor nutritional factors
Tabacco (cigarette, pipe, cigar and bidis)
1964 first Surgeon General’s report
1986 IARC Gp I carcinogen for human
60/4,000
attributable 90% lung cancer
ETS:  about 20%
EPA report ETS a human lung carcinogen
Air pollution: vs. 0.28
Occup: Chloromethyl ethers, chromium, asbestos, PAHs, radon 7

8. Taiyuan, Air Pollution and Lung Cancer: 400 cases/ 400 controls
China-UCLA Lung Cancer Consortium
Taiyuan, Air Pollution and Lung Cancer: 400 cases/ 400 controls
Jiangsu: Epidemiology of Top 4 Cancers (Lung, esophagus, liver and stomach)
Fuzhou, Air Pollution and DNA Repair Genes and Lung Cancer: 600 cases and 600 controls

9. Specific Aims of the China-UCLA Lung Cancer Consortium
To identify novel environmental risk and protective factors
To evaluate genetic susceptibility
To assess potential environment-gene interactions

10. Indoor Air Pollution in China, Preliminary Results

11. TaiYuan Project
Cases: 396 newly diagnosed patients with lung cancer from major cancer hospitals in this city between ;
Control: 465 healthy control from the same source population;
Epidemiological data were collected by in-person interview using a standard questionnaire;

12. Second Hand Smoking (SHS) and Lung Cancer Risk among Non-Smokers (Taiyuan)
Case
Control
AOR(95%CI)
N %
Male & Female
71 (40.1)
129 (45.4) 1
Household
106 (59.9)
155 (54.6)
1.01 ( )
117 (66.1)
198 (69.7)
Workplace
60 (33.9)
86 (30.3)
1.84 ( )
Neither
42 (23.7)
91 (32.0)
Household / workplace
104 (58.8)
145 (51.1)
1.57 ( )
Household + workplace
31 (17.5)
48 (16.9)
1.64 ( )
Female
57 (35.2)
83 (38.3)
105 (64.8)
134 (61.8)
1.20 ( )
113 (69.8)
167 (80.0)
49 (30.3)
50 (23.0)
1.86 ( )
38 (23.5)
67 (30.9)
94 (58.0)
116 (53.5)
1.54 ( )
30 (18.5)
34 (15. 7)
2.09 ( )

13. Household Second Hand Smoking Exposure and Lung Cancer Risk among Non-smokers
Relationship
ETS
Case
Control
AOR&95%CI No 71
129
Any
Yes
106 (60)
155(54.6)
1.18 ( )
Spouse
91(51)
102(35.9)
1.53 ( )
Only others 15 53
0.53 ( )
Spouse + others 17 30
0.94 ( )

15. Indoor Air pollution Index and Lung Cancer Risk
Case
Control
AOR (ALL)
AOR(ADC)
AOR(SCC)
69 (18.0)
199 (43.0) 1
1--2
127 (33.1)
157 (33.9)
2.13
( )
1.76
( )
2.61
( )
3--5
160 (41.7)
99 (21.4)
4.52
( )
4.04
( )
3.58
( ) 6+
28 (7.3)
8 (1.7)
9.28
( )
14.49
( )
7.60
( )
Ptrend
P<0.0001
Index: Sum of Indoor Air Pollution Exposure
Cooking fuel(0,1), heating (0,1,2), Ventilation(0,1,2), Fry cooking(0,1), SHS (0,1)

16. Indoor Particle Exposure Measurement
A Particle Mass Monitor
PM1, PM2.5, PM 7, PM10, TSP
Indoor: Living room, bed room, kitchen;
--Twice for each room
Outdoor
Two season: Heating season/non-heating season

17. PM1 comparison among cases and controls
0.02
0.04
0.06
0.08
0.1
0.12
mg/m3
Living
room
Bed room
Kitchen
PM1 Case
PM1 Control
Summer
Winter
Correlation between Indoor Air pollution Index and PM1 Concentration
Living Room
Bed room
Kitchen
Indoor
Index
Coefficients
0.23
0.09
0.1 P
0.011
0.077
0.067

18. Indoor PM1 and Lung Cancer Risk
AOR(Summer)
AOR(Winter)
Living room
All*
2.48 ( )
1.8 ( )
Non-smoker
4.06 ( )
3.18 ( )
Per 10ug/m3
1.28( )
1.31( )
Bed room
All
2.52 ( )
1.82 ( )
3.37 ( )
3.68 ( )
1.26( )
1.30( )
Kitchen
2.43 ( )
1.76 ( )
3.41 ( )
2.5 ( )
1.28( )
1.38( )
* : PM1: High (>50%) vs Low (<50%)

19. Conclusion
Indoor Air pollution, SHS, solid fuel exposure, cooking, poor ventilation may be associated with lung cancer
Indoor PM1 concentration may be associated with lung cancer
Potential gene-environmental exposure interaction.

20. Second Hand Smoking and Lung Cancer Among Non-smokers, International Lung Cancer Consortium (ILCCO)

21. Second hand smoking and lung cancer among 7,170 cases and 9,186 controls, ILCCO
Site
Adjusted OR
95% CIs
All sites
1.21
1.08, 1.35
Squamous
1.17
0.95, 1.43
Adenocarcinoma
1.04, 1.40
SCLC
1.52
1.12, 2.05
NSCLC
1.20
1.06, 1.36

22. ETS and lung cancer among non-smokers, 2,218 cases and 6,243 controls, ILCCO
Site
Adjusted OR
95% CIs
All sites
1.33
1.18, 1.50
Squamous
1.38
0.98, 1.98
Adenocarcinoma
1.26
1.08, 1.46
SCLC
2.92
1.55, 5.48
NSCLC
1.30
1.14, 1.49

23. SNPs Associated with Lung Cancer among Non-Smokers
OGG1 S326C
XRCC1 R194W
XPD D312N

27. G1 S G2 M
P53
Cyclin D1
P16
Environmental Carcinogens / Procarcinogens Exposures
Nitrosemins, Xenobiotics,
Diet/nutrient
Active carcinogens
Detoxified carcinogens
DNA Damage
Normal cell
Carcinogenesis
Programmed cell death
Tobacco/alcohol
infection
Diet and nutritional factors
CYP2E1
GSTP1
mEH
NQO1
XRCC3
GSTM1
Theoretical model of gene-environmental interaction pathway for lung cancer susceptibility
Ile105Val 
Ala114Val
Tyr113His
His139Arg
Pro187Ser
Null 
Ala146Thr
Arg72Pro
G870A
Diet/nutrient
Free radicals
Oxidative Stress
DNA damage repaired
Defected DNA repair gene
If DNA damage not repaired G0
If loose cell cycle control 27

28. DNA repair Risk of Lung Cancer Associated with Low DRC Odds Ratio6
In Vitro Adduct Assay (genomic DNA) 5
Trend test : P < 0.001 4 3
Odds Ratio 2 1
Ist
2nd
3rd
4th
DRC (%) by Quartile
High Low
Li et al, Cancer Res., 2001
Friedberg, Nature Reviews Cancer 2001; 1: 22-33

29. Indoor Air Pollution, XRCC1 194 Polymorphism and Lung Cancer
100 OR 10 1
0.1
Arg/Arg
Any Trp
Arg/Arg
Any Trp
Arg/Arg
Any Trp
Indoor(-)
Indoor(+)
Indoor(++)

34. Fuzhou Medical University
Acknowledgements
Fudan University
Lina Mu
Shunzhang Yu
Qingwu Jiang
Fuzhou Medical University
Lin Cai
Taiyuan CDC
Li Liu
Jianping Shi
Baoxing Zhao
UCLA
Shun-Chun Chuang
Yifang Zhu
Jiangsu CDC
Jinkou Zhao
Hua Wang
Shanxi Tumor hospital
Ruigui Niu
XiaoYou Han
The study was supported in Part by National Natural Science Foundation of China

35. Acknowledgements
T32 CA09142 (PI: Zhang), NIH/NCI, Cancer Epidemiology Training Program
P50 CA90833 (Project PI: Zhang),NIH NCI. Molecular Epidemiology of Lung Cancer
D43 TW S2 (Co-PIs: Zhang/ Detels) NIH/Fogarty. UCLA Fogarty AITRP: Molecular Epidemiology of HIV-AIDS-related Malignancies in China
D43 TW S (Co-PIs: Zhang/Detels). NIH Fogarty: International Training in Epidemiology Related to AIDS: HIV-AIDS-related Cancer in China

37. UCLA is the largest comprehensive university in West Coast
with shortest distance to China
UCLA