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

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Source: Peto J, 2001 4

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

Age-standardized Incidence Rates For Lung Cancer Source: Figure 5: Parkin DM, et al. CA Cancer J Clin [2005]; 55: 74-108

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: 1.1-5.2 vs. 0.28 Occup: Chloromethyl ethers, chromium, asbestos, PAHs, radon 7

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

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

Indoor Air Pollution in China, Preliminary Results

TaiYuan Project Cases: 396 newly diagnosed patients with lung cancer from major cancer hospitals in this city between 2006-2007; Control: 465 healthy control from the same source population; Epidemiological data were collected by in-person interview using a standard questionnaire;

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 (0.67-1.51) 117 (66.1) 198 (69.7) Workplace 60 (33.9) 86 (30.3) 1.84 (1.17-2.88) Neither 42 (23.7) 91 (32.0) Household / workplace 104 (58.8) 145 (51.1) 1.57 (0.99-2.49) Household + workplace 31 (17.5) 48 (16.9) 1.64 (0.89-3.01) Female 57 (35.2) 83 (38.3) 105 (64.8) 134 (61.8) 1.20 (0.78-1.85) 113 (69.8) 167 (80.0) 49 (30.3) 50 (23.0) 1.86 (1.14-3.04) 38 (23.5) 67 (30.9) 94 (58.0) 116 (53.5) 1.54 (0.94-2.54) 30 (18.5) 34 (15. 7) 2.09 (1.07-4.05)

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 (0.80-1.74) Spouse 91(51) 102(35.9) 1.53 (1.00-2.34) Only others 15 53 0.53 (0.28-1.01) Spouse + others 17 30 0.94 (0.48-1.84)

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 (1.46-3.11) 1.76 (0.96-3.20) 2.61 (1.37-4.97) 3--5 160 (41.7) 99 (21.4) 4.52 (2.97-6.88) 4.04 (2.16-7.57) 3.58 (1.71-7.48) 6+ 28 (7.3) 8 (1.7) 9.28 (3.79-22.72) 14.49 (4.93-42.63) 7.60 (1.63-35.53) 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)

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

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

Indoor PM1 and Lung Cancer Risk AOR(Summer) AOR(Winter) Living room All* 2.48 (1.15-5.37) 1.8 (0.89-3.63) Non-smoker 4.06 (1.17-14.13) 3.18 (0.87-11.64) Per 10ug/m3 1.28(1.23-1.45) 1.31(1.17-1.47) Bed room All 2.52 (1.4-4.52) 1.82 (1.03-3.23) 3.37 (1.31-8.7) 3.68 (1.22-11.08) 1.26(1.16-1.37) 1.30(1.19-1.42) Kitchen 2.43 (1.35-4.39) 1.76 (0.98-3.17) 3.41 (1.32-8.78) 2.5 (0.86-7.28) 1.28(1.17-1.39) 1.38(1.24-1.54) * : PM1: High (>50%) vs Low (<50%)

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.

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

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

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

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

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

DNA repair Risk of Lung Cancer Associated with Low DRC Odds Ratio 6 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

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(++)

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

Acknowledgements T32 CA09142 (PI: Zhang), NIH/NCI, Cancer Epidemiology Training Program P50 CA90833 (Project PI: Zhang),NIH NCI. Molecular Epidemiology of Lung Cancer D43 TW000013-21S2 (Co-PIs: Zhang/ Detels) NIH/Fogarty. UCLA Fogarty AITRP: Molecular Epidemiology of HIV-AIDS-related Malignancies in China D43 TW000013-20S (Co-PIs: Zhang/Detels). NIH Fogarty: International Training in Epidemiology Related to AIDS: HIV-AIDS-related Cancer in China

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