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CARCINOMA LUNG IN NON-SMOKERS: A Systematic Literature Review.

CARCINOMA LUNG IN NON-SMOKERS: A Systematic Literature Review. Dr. Qureshi, M.S. 1 Dr. Siddiqui, U.A. 2 Dr. Shah, P. 3 Dr. Hodson, M.E 4 Dr. Mohammad Saif Qureshi: MSc Respiratory Medicine Imperial College London.

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CARCINOMA LUNG IN NON-SMOKERS: A Systematic Literature Review.

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  1. CARCINOMA LUNG IN NON-SMOKERS: A Systematic Literature Review. Dr. Qureshi, M.S.1Dr. Siddiqui, U.A.2 Dr. Shah, P.3 Dr. Hodson, M.E4 Dr. Mohammad Saif Qureshi: MSc Respiratory Medicine Imperial College London. Dr. Uzma Abid Siddiqui: MSc Global Health-Tutor; Trinity College, Dublin, Ireland Dr. Pallav Shah: Supervisor/Consultant Respiratory Physician at Royal Brompton Hospital/Chelsea & Westminster Hospital. Senior Lecturer at the National Heart and Lung Institute. Dr. Margaret Hodson Professor of Respiratory Medicine, Senior Research Investigator at the National Heart and Lung Institute, Imperial College London / Consultant Physician and Director of Medical Education for the Royal Brompton Hospital.

  2. Rationale for Study • “Lung cancer risk among the non-smokers is an increasingly important issue." As the rate of lung cancer among people who have never smoked is higher than previously expected or speculated! • Lung cancers occur about thirty times more frequently In smokers, but non-smoker cannot escape the ill fate of getting it. It’s been proven that 15-25% of non-smokers are seemed to be affected by this deadly killer.

  3. 1. Lung cancer in never smokers (LCNS) Sun S., Schiller J.H. & Gazdar A.F. Nat Rev Cancer, October 2007: 7: 778-7902. www.lungcancercoalition.org/en/pages/facts3. Parkin DM, Bray F, Ferlay J and Pisani P. CA Cancer J Clin 2005; 55: 74-108. http://www.google.co.uk/imgres?imgurl=http://www.mycancer.co.za/lung/lungs.jpg

  4. Aim of the Study • To systematically review the published literature on the relationship between the lung cancer and its possible risk factors mainly among the non–smoking population and to present an analysis of these relationships.

  5. Specific objectives • .......whether the causative factors involved in causing carcinoma lung affected smokers alone or non-smokers as well. • ....... what proportions of non-smokers were suffering from lung cancer secondary to these risk factors according to the selected studies.

  6. Significance of this study • Although it has long been established that cigarette–tobacco smoking is the main culprit behind so many deaths! But it cannot fully explain the epidemiological and biological characteristics of lung cancer. • It is essential to consider the very long list of other risk factors especially in the non-smoking population that might not be blamed equally along with the cigarette/tobacco smoking but not to be ignored either.

  7. Histo-pathogenesis of Lung Cancer There are two main sub-groups of lung cancers: • Small cell lung cancers (SCLC) -20%* • Non-small cell lung cancers (NSCLC) -80%* The main types of (NSCLC) are: • squamous cell carcinoma ~35% • Adenocarcinoma~27%* • Large cell carcinoma ~ 10%* *of all lung cancer cases respectively in the UK.7

  8. lung Cancer Facts & figures in Ireland (2005-2007)* • Annual average : 1810 cases • Incidence rate among Females:33.41* • Incidence rate among Males: 56.3* • Mortality rate among Females: 28.6* • Mortality rate among Males: 50.9* Source: National Cancer Registry Ireland, 2009* cases per 100,000 persons per year * deaths per 100,000 persons per year*

  9. lung Cancer Facts & figures in UK. (2007-2008)* • Annual average : 39,473 cases • Incidence rate among Females: 37.6* • Incidence rate among Males: 59.4 * • Mortality rate among Females: 32.0 * • Mortality rate among Males: 51.0 * Source: Cancer Research UK, 2010.* cases per 100,000 persons per year European age-standardised * deaths per 100,000 persons per year European age-standardised *

  10. Main determinant of lung cancer risk • Environmental factors / Air pollution • Lifestyle factors • Diet / Alcohol use • History of lung diseases • Previous primary cancer • Radiotherapy • Reproductive /Endocrine factors • Occupational /Industrial exposure • Family history, Genetic predispositions • Physical activity • Other factors e.g. HIV/AIDS, People with antibodies to Chlamydia pneumoniae, SLE and Klinefelter syndrome

  11. The importance of this Research • The evidence associating lung cancer with the a-fore mentioned risk factors among the non-smoking population is weak to date. • We tried to find the role of any of these risk factors among non-smokers. • To identify a strong independent risk factor.

  12. RESEARCH METHODOLOGY: (1) Study design: Retrospective Systematic Literature Review. Inclusion criteria: • Studies on the risk factors for Carcinoma Lung • Studies including or considering non-smokers. • Studies on humans only. • Studies done in English or translated in to English. • Studies from all around the world. Exclusion criteria: • Studies done on animals. • Studies done in different languages that are not translated. • Studies solely based on the effects of smoking on Lung Cancer.

  13. RESEARCH METHODOLOGY:(2) Data Source • We analyzed articles through Pubmed via the NCBI Entrez system (2003-2009). • Imperial College Meta-Library. Study Selection • Inclusion/exclusion criteria. • Full- length text , peer-reviewed reports of cohort studies, cross-sectional studies or case control studies. • Studies on the presence of risk factors associated with lung cancer and their association among the non- smoking population. • Only those studies with the most detailed information for both outcome and exposure. • Studies involved in the aetiology of Lung Carcinoma irrespective of their direct or indirect relationship with passive smoking, indoor and outdoor/environmental air pollution.

  14. Flow Diagram for study selection and exclusion There were 901 studies identified and screened under the following keywords; lung cancer, never/ non-smokers, risk factors 593 studies were excluded because they were irrelevant to our study • 284 studies were excluded because; • They did not include any risk estimates HR or RR etc./confidence interval (CI) [except one by Wakelee et al,33] • They were reviews (46), • They replicated/duplicated other studies, • Only included smoking as a risk factor. 308 studies were selected that covered the research topic. 24 studies were finally selected. Family history; 4 Occupational Hazards/ Asbestos & Silica Exposure; 3 Menstrual and Reproductive factors; 4 Environmental air pollution factors; 3 Genetic factors; 2 Cooking Fumes Exposure; 2 Radon exposure; 1 Geographic, racial & gender differences; 3 Non-neoplastic causes; 2

  15. Data Extraction • Studies were identified and screened by their titles and abstract details using these key words: “Lung cancer susceptibility, Never/Non-Smokers, Risk factors.” • For every eligible study, detailed information was collected regarding the: • Year and country of study. • study design, population & sample size, choice of controls. • definition and measurement of risk factors for lung cancer. • type of outcome in respect of the study participant’s smoking or non- smoking status and 95 per cent confidence interval (CI).

  16. RESULTS (1) • Study Characteristics of Research Papers included in the Systematic Literature Review

  17. RESULTS (2) Outcomes from studies regarding Lung Cancer and it’s risk factors in relation to Non-Smokers

  18. Total No; of Subjects in relation to Lung Cancer and Non-smokers 26757 (1%) 8087 (30.2%) 2639 (9.9%)

  19. Our Analysis (1) Out of the ‘24’ selected studies • all study subjects were between the age range of >40-60+ (mean age 57 years). • ‘8’ Studies employed females only. • ‘15’ had both male and female subjects for their analysis. • ‘1’ study considered males only. • 10 studies dealt with non-smokers. • 14 studies employedboth smokers and non-smokers.

  20. Our Analysis (2) • Familial & Genetic Risk Factors: • 3 out of 4 studies suggested that having a family history of lung cancer was found to be a strong predictor of lung cancer among female non-smokers. • An association between genetic polymorphisms and lung cancer exists. • Hormonal and Reproductive Factors: • There is in disputable evidence with regards to the presence of oestrogen receptors in lung tumours and the role of oestrogen in carcinogenesis. • ETS exposure: • A prominent risk factor in males & females, smokers & non-smokers. However, few studies claim ETS to play no or a relatively weak role in lung carcinogenesis in non-smokers. • Cooking Fumes Emissions (CFE): • A significant contributing factor in Lung cancer etiology. Study (12) found adenocarcinoma as the most frequently linked sub-type.

  21. Our Analysis (3) • Geographic, Gender and Racial Risk Factors: • Studies 17 & 18 concluded a higher incidence rate among women. But study no; 16 showed that mortality rates were higher in non-smoking males. • Occupational Hazards & Radon exposure : • All of these studies conclude that Asbestos, and other hazards play a vital role in Lung cancer occurrence both in smokers and non-smokers. While Study no; 21 observed that the risk is around three times greater in non/never smokers than in smokers4 • Study no; 22 showed Radon exposure was associated with lung cancer risk among smokers • Non neoplastic diseases of Lung: • Study no; 23 found that female non-smoking subjects with systemic sclerosis showed a higher risk of lung cancer. But increased mortality was seen among male non-smokers in Study no; 24.

  22. Study Limitations • It was difficult to confirm how the subjects were recruited especially on the basis of their smoking status. • The present study was unable to identify differences between men and women. • lack of consistent information & time constraints.

  23. Conclusion • There is no doubt in the occurrence of lung cancer among non-smokers. • Smoking and non-smoking lung cancer sufferers are different in etiology and performance but also in their response to different risk factors &even in response to treatment . • In-depth insight is necessary in to the potential patho-genetic mechanisms that link these risk factors and further proofs for an epidemiological/ biologic disparity in lung cancer between smokers and non-smokers.

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  25. THANK YOU!

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