1. Lung Cancer incidence in Māori – increased susceptibility mediated through COPD. Dr Rob Young BMedSc, MBChB, DPhil (Oxon) FRACP, FRCP Associate Professor of Medicine, Department of General Medicine, Auckland City Hospital, University of Auckland.

2. 22 Disclosures: Dr Robert Young Never used funding from the tobacco industry Associate Professor in Medicine and Molecular Genetics, University of Auckland, NZ Received travel grant and honorarium for talks on smoking cessation and COPD from GSK and Astra-Zeneca Received research funds from Johnson and Johnson Chief Scientific Officer of Synergenz BioScience Ltd who helped fund genetic epidemiology studies (Founder and Advisor)

3. 3 Lung Cancer incidence in Māori – increased susceptibility mediated through COPD. 1.Risk factors for lung cancer 2.COPD and risk of lung cancer 3.Lung cancer and Ethnicity 4.Lung cancer in Māori vs European – current study 5.Implications in future prevention

4. 4 Lung Cancer incidence in Māori – increased susceptibility mediated through COPD. 1.Risk factors for lung cancer 2.COPD and risk of lung cancer 3.Lung cancer and Ethnicity 4.Lung cancer in Maori vs European – current study 5.Implications in future prevention

5. 5 Risk factors for lung cancer All Ethnicities Increasing age Smoking exposure Presence of COPD * * * Other aero-pollutant exposures (asbestos, radon, cadmium) Ethnicity and genetic factors ** Diet and Education (SES) LC Incidence ≠ LC Mortality Poor access to healthcare/screening, delayed presentation, reduced treatment options and reduced survival do not affect incidence (but can increase mortality) Incidence is a function of “susceptibility”

6. 6 Risk factors for lung cancer Multivariate Analysis Hopkins and Young, 2015 (N=18,714) Risk for lung cancer -Smoking status -Increases with age >45 yo -COPD and its severity

7. 7 Spirometry-based COPD (42%) CT-based Emphysema (42%) Normal lungs (42%) Young et al. Eur Respir J 2012: 40 1063-4 Lung cancer detection rate (LCDR) over 3 yrs of screening in the Pittsburgh Lung Screening Study (PLuSS)

8. 8 Spirometry-based COPD (42%) CT-based Emphysema (42%) Normal lungs (42%) LC 9 58 17 15 573 913 1495 558 Absolute numbers Young et al. Eur Respir J 2012: 40 1063-4 Lung cancer detection rate (LCDR) over 3 yrs of screening in the Pittsburgh Lung Screening Study (PLuSS) 85% of all lung cancers developed in those with COPD ± CTE

9. 9 Spirometry-based COPD (42%) CT-based Emphysema (42%) Normal lungs (42%) LC 9 58 17 15 573 913 1495 558 4.5% 5.1% 1.0% Absolute numbers Lung cancer rates* Young et al. Eur Respir J 2012: 40 1063-4 Lung cancer detection rate (LCDR) over 3 yrs of screening in the Pittsburgh Lung Screening Study (PLuSS) 85% of all lung cancers developed in those with COPD ± CTE LCDR was 4-5 fold higher in those with COPD ± CTE

10. 10 Lung Cancer incidence in Māori – increased susceptibility mediated through COPD. 1.Risk factors for lung cancer 2.COPD and risk of lung cancer 3.Lung cancer and Ethnicity 4.Lung cancer in Maori vs European – current study 5.Implications in future prevention

11. Ethnicity and lung cancer incidence – US data Men: Caucasian vs Hawaiian Same smoking status, duration, quitting and intensity. College education (74% vs 42%) –SES effect? Men: Hawaiian vs Hispanic Same smoking status, duration, quitting but lighter smokers, 30% college educated Men: Hawaiian vs Asian Same smoking status, duration, quitting and intensity, similar college educated Socio-economic status (SES) and smoking rates does not fully explain the differences across ethnicities Blakely et al. Lancet 2006 Maori disparity in mortality 59yo 57yo 62yo 60yo 61yo NEJM Haiman et al. 2006 Age-standardised Lung Cancer Incidence by ethnicity (men and women) Average age at diagnosis

12. Ethnicity and lung cancer incidence – US data 12 Men: Caucasian vs Hawaiian Same smoking status, duration, quitting and intensity. College education (74% vs 42%) –SES effect? Men: Hawaiian vs Hispanic Same smoking status, duration, quitting but lighter smokers, 30% college educated Men: Hawaiian vs Asian Same smoking status, duration, quitting and intensity, similar college educated Socio-economic status (SES) and smoking rates does not fully explain the differences across ethnicities Blakely et al. Lancet 2006 Maori disparity in mortality Age-standardised Lung Cancer Incidence by ethnicity (men and women) 59yo 57yo 62yo 60yo 61yo NEJM Haiman et al. 2006 Average age at diagnosis

13. Risk of lung cancer according to smoking intensity and ethnicity – US data 13 Relative Risk (A. American) Smoking Intensity (cigs/day) P<0.001 NEJM Haiman et al. 2006 Smoking dose-response effect lost in African American and Hawaiian.

14. Risk of lung cancer according to smoking intensity and ethnicity – US data 14 Relative Risk (Caucasian) NEJM Haiman et al. 2006 Lower lung cancer risk Greater lung cancer risk Ethnicity effect seen in smokers is absent in non-smokers

15. Conclusions and Editorial Comment In non-smokers, no difference (disparity) in lung cancer incidence (or risk) between Hawaiian and Caucasian. Smoking “creates” the disparity through unmasking differences in susceptibility across ethnic groups (ie. smoking x ethnicity effect). High susceptibility groups (Hawaiians and African Americans) are characterised by elevated risk even at low cigarette exposures. Tobacco control measures that eliminate smoking all together will be the only effective way of reducing disparities. 15

16. Ancestral origins of Māori and Hawaiians 16 Shared cultural and genetic factors

17. Recent press releases from Lancet study 17 “Maori have the highest rate of lung cancer of all the populations in the 4 high income countries studied” “Tobacco control in NZ has failed Māori” “The country needs Māori to lead a new approach to cutting smoking rates” “Māori are treated differently in the health system” “Reporting by ethnicity is a good start to understanding what needs to be done”

18. 18 Risk factors for lung cancer - data for Māori All Ethnicities Increasing age Smoking exposure# Presence of COPD * * * Other aero-pollutant exposures (asbestos, radon, cadmium) Ethnicity and genetic factors Diet and Education (SES)# Māori (cf NZ Europeans) -Lung cancer rates - 3-4x -Smoking rates - 2x -Late presentation, advanced stage and less curative treatment -Worse Survival (50%) -# (Blakely et al. Lancet 2006) Basis of higher incidence – greater susceptibility ± COPD related?

19. 19 Take home messages Greater smoking prevalence and lower socioeconomic position contribute to the ethnic inequalities in mortality in New Zealand (Māori have highest mortality). These two factors account for up to 60% of the difference in mortality with smoking accounting for 10% and SEP about 50%. Conclusion: Smoking and SEP are not the full explanation for worse health outcomes in Māori. Lancet 2006: 368: 44-52.

20. Māori vs European Lung cancer series - 2008 20 Demographic variables Māori n=95 NZ European n=417 Mean Age at Diagnosis (SD)↓ 63 (10)71 (11) % Male49%55% % Never Smoker ↓1% 8% % Smoking at Diagnosis ↑ 65% 36% Mean Pack-years (SD) 39 43 Self-reported COPD ↑ 58%**48% NSCLC vs SCLC84% vs 16%88% vs 12% NSCLC - Early stage↓ 23%33% SCLC - Limited↑ 47%30% Stevens et al. J Thorac Oncol 2008; 3: 237-244. Similar smoking

21. Risk of COPD in Māori 21 Asthma Foundation: Literature Review: Respiratory Health for Maori 2009

22. COPD hospitalisation by age and ethnicity 22 Comparable admission rates seen in non-Māori 15 yrs older than Māori

23. 23 Lung Cancer incidence in Māori – increased susceptibility mediated through COPD. 1.Risk factors for lung cancer 2.COPD and risk of lung cancer 3.Lung cancer and Ethnicity 4.Lung cancer in Māori vs European – current study 5.Implications in future prevention

24. Māori vs European Lung cancer series 24 Demographic variables Māori n=473 NZ European n=417 Mean Age at Diagnosis (SD) ↓ 61 (9) 67 (10) Male43%51% Smoking Status Smoking at Diagnosis Never smokers ↑ 67% ↓2% 36% 7% Mean Pack-years Male4245 Female3736 Combined3941 Cigs/day # 1716 RJ Hopkins, C Kendall, Young et al. 2015 – Unpublished data Similar to Stevens study Similar smoking

25. 25 Spirometry Māori n=473 NZ European n=417 Lung function Spirometry Available 69% (326) 62% (259) Mean FEV1% pred.↓ 64%72% Mean FEV1/FVC0.64 COPD Total 64% (209) 65% (168) GOLD 1 ↓ 13% (27) 20% (33) GOLD 2 ↑ 59% (122) 54% (91) GOLD 3-4 ↑ 29% (59) 26% (44) P=0.08 Hopkins, Kendall, Young et al. 2015 – Unpublished data

26. 26 Lung cancer - age distribution by ethnicity P<0.0001 Hopkins, Kendall, Young et al. 2015 – Unpublished data

27. Lung cancer - age distribution by ethnicity 27 85% of lung cancers in Māori before 70 yo (63% in Caucasians) Hopkins, Kendall, Young et al. 2015 – Unpublished data

28. 28 Hopkins, Kendall, Young et al. 2015 – Unpublished data Distribution of smoking exposure by ethnicity in lung cancer % Smoking exposure – Pk years

29. 29 P<0.05 Hopkins, Kendall, Young et al. 2015 – Unpublished data COPD prevalence in LC cases according to smoking exposure 64% vs 30% Smoking exposure – Pk years COPD Prevalence

30. Risk of lung cancer according to smoking intensity and ethnicity – US data 30 Relative Risk Smoking Intensity (cigs/day) P<0.001 NEJM Haiman et al. 2006

31. 31 P<0.05 Hopkins, Kendall, Young et al. 2015 – Unpublished data Lung Function (FEV1) according to smoking exposure %Predicted FEV1 Smoking exposure – Pk years

32. 32 Lung cancer histology distribution by ethnicity Māori lung cancer cases More Aggressive More SCLC (22% vs 18%) More Non-small cell (14% vs 10%) More Squamous (26% vs 24%) “Less Aggressive” Less Adenocarcinoma (32% vs 43%) P=0.025 Hopkins, Kendall, Young et al. 2015 – Unpublished data

33. Findings suggesting greater susceptibility to lung cancer 33 1.Younger age of onset despite comparable smoking exposure 2.Worse lung function despite comparable smoking history 3.Loss of the expected dose-response relationship with smoking at lower levels of exposure 4.Greater prevalence of more aggressive forms of lung cancer

34. Possible reasons for higher rates (and susceptibility) of lung cancer in Māori 34 1.Cannabis use in NZ study - lifetime use not associated with an increased lung cancer risk overall (restricted to heavy users) - accounted for only 5% of lung cancer in those <55 yr old 2.Socioeconomic factors in NZ study - lung cancer risk ↑2x with low SEP, ↑4x with Māori ethnicity 3. Earlier age at onset of smoking (studies show 16 yo and 17 yo) 4. Maternal smoking rates in Māori women relative to European - may contribute to greater susceptibility (COPD related)

35. Lung cancer Survival data for 2003-2007 35 Hopkins, Kendall, Young et al. 2015 – Unpublished data ↑ susceptibility contributes to disparity in mortality?

36. Conclusions Lung cancer in Māori is characterised by…. Earlier age of diagnosis (6-8 yrs younger) despite comparable smoking exposure Worse spirometry, more aggressive cancer histology and greater susceptibility (FEV 1 ) to the effects of smoking Two fold greater mortality likely explained in part by a greater susceptibility to the pulmonary effects of smoking 36

37. 37 Lung Cancer incidence in Māori – increased susceptibility mediated through COPD. 1.Risk factors for lung cancer 2.COPD and risk of lung cancer 3.Lung cancer and Ethnicity 4.Lung cancer in Maori vs European – current study 5.Implications in future prevention

38. National Respiratory Strategy - Actions Current projections for smoking prevalence suggest that the 2025 smoke-free goal will not be achieved. Many new strategies are needed and a formalised national plan needs to be developed. Ensure there are specific actions towards lowering smoking rates for Maori and Pacific peoples. These initiatives are designed and delivered by Maori and Pacifica. Call to action for everybody working in respiratory health to increase our efforts to increase quit rates, diagnose COPD and be mindful of the risks of lung cancer. 38

39. 39 Thank you 4.5% 5.1% 1.0%