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A STATISTICAL STUDY OF THE RISK FACTORS FOR URINARY BLADDER CANCER IN PAKISTAN BY MUHAMMAD RIAZ AHMAD 09-GCU-Ph.D-STAT-2004 DEPARTMENT OF STATISTICS GC UNIVERSITY, LAHORE (PAKISTAN) iv A thesis titled A STATISTICAL STUDY OF THE RISK FACTORS FOR URINARY BLADDER CANCER IN PAKISTAN Submitted to the GC University, Lahore For the award of degree of PhD in STATISTICS BY MUHAMMAD RIAZ AHMAD 09-GCU-PhD-STAT-2004 DEPARTMENT OF STATISTICS GC UNIVERSITY, LAHORE (PAKISTAN) i DECLARATION I, Muhammad Riaz Ahmad, Registration No. 09-GCU-Ph.D-STAT-2004 student of Ph.D in the subject of Statistics, Session 2008-2011 is hereby declared that the matter printed in the thesis “A Statistical Study of the Risk Factors for Urinary Bladder Cancer in Pakistan” is my own work and has not been printed, published and submitted as research work, thesis or publication in any form, in any university, research institution etc., in Pakistan or abroad by someone else. Dated: --------------- Muhammad Riaz Ahmad RESEARCH COMPLETION CERTIFICATE Certified that the research work contained in this thesis titled “A Statistical Study of the Risk Factors for Urinary Bladder Cancer in Pakistan” has been carried out and completed by Muhammad Riaz Ahmad, Registration No. 09-GCU-Ph.D-STAT-2004 for the completion of Ph.D degree. Supervisor Prof. Dr. Muhammad Khalid Pervaiz Dean, Faculty of Arts and Social Sciences Chairperson, Department of Statistics, G.C. University, Lahore. Dated: -------------- Submitted through Prof. Dr. Muhammad Khalid Pervaiz Dean, Faculty of Arts and Social Sciences Chairperson, Department of Statistics, G.C. University, Lahore. Controller of Examinations G.C. University, Lahore i Acknowledgement I am very grateful to Almighty Allah, the most beneficial and merciful, who gave me courage, potential, energy, patience and spirit of hard work to complete this dissertation, which I could not complete successfully without his blessing. A tribute to His beloved Holy Prophet (Peace Be Upon Him), being a follower to find new things and explore the nature. It is a great pleasure and honor to express my feelings, gratitude’s and thanks to Prof. Dr. Muhammad Khalid Pervaiz Dean, Faculty of Arts & Social Sciences, Chairperson, Department of Statistics G.C. University, Lahore for his kind and sincere efforts to complete this research work. It would have been difficult for me to complete this research without his guidance, encouragement and sharing of knowledge. The role of HEC towards higher education in Pakistan is remarkable and can never be ignored. I would never be able to complete my higher education (M.Phil and PhD) without the support of Higher Education Commission. In this connection, the guidance, assistance and services provided by the Miss Madiha Anwar Research Associate HEC during the whole study period of PhD are appreciable. I am thankful to Principal Rana Abdul Qayyum, Prof. Muzaffer Ali Zia, Prof. Dr. Muhammad Naeem, Prof. Ikhlaq Hussain Shah of Govt. College, Jaranwala, Dr. Zahid Ahmad, Govt. College, Ravi Road, Lahore, Dr. Ahmad Faisal Siddiqi, University of Management &Technology, Lahore, Muhammad Ibrahim, Govt. Dyal Singh College, Lahore and Bashir Ahmad (Principal, Govt. M. D College, 41-JB, Faisalabad) for their co-operation and encouragement during my studies. Furthermore, I can not ignore the cooperation of my class fellows, Mr. Abbdul Quyyum, Mr. Muhammad Hamid Mehmood, Ms. Asifa Kamal and Ms. Asma Zeb, Muhammad Ghias, Ms. Uzma Hafeez and Ms. Maryam Siddiqa during my studies. The services and cooperation of all the heads and doctors of the hospitals from which I collected data related to my study were also remarkable and I am highly obliged to all. ii I am unable to pay thanks for the kindness and loving attitude of my mother who prays day and night for my success. The completion of this research work is not possible without her prayers and encouragement. I do express good feeling and sincere gratitude to my wife whose accommodating behaviour made it possible for me to complete the research and my special thanks to my children for their support, understanding and patience towards my long working hours and for there less demanding behavior during the course of this study. In the last but not the least my acknowledgements are for all my fellows and well-wishers who have encouraged me. MUHAMMAD RIAZ AHMAD iii ABSTRACT This study investigated the effect of different risk factors in the occurrence of urinary bladder cancer in Pakistan on the basis of a case control study using both descriptive and analytical approaches. A sample of 900 subjects including 300 cases and 600 controls was selected from different areas of Pakistan including headquarter of all four provinces and federal area (Islamabad) through a questionnaire. The requisite information was obtained from all the patients/ controls by the researcher using the direct interview method. From the headquarters of Khyber PukhtoonKhwa, Sindh, Baluchistan and federal area (Islamabad), 150 subjects (including cases and controls) were taken from wards of two selected public hospitals but from the headquarter of the Punjab (Lahore), 300 subjects (including cases and controls) were taken from the wards of four selected public hospitals. Controls are taken by matching the gender, area of residence and age above 40 years. About 22 factors with sub categories were included in the study. For bivariate analysis, the chi-square, phi/v statistics and Kandall’s tau-b are used. For the purpose of multivariate analysis, the binary logistic regression was run by using the SPSS (version-16) to observe the significant risk factors and prediction of the model. In the descriptive analysis, it was observed that risk of bladder cancer increases with an increase in the number of cigarettes smoked per day, years of smoking and risk decreases when the stop smoking period increases. Further more, similar results were observed in the bivariate analysis. In the overall analysis, the six factors including hair dye, chemical exposure, family history, cigarette smoking, fried items and fats items are found to be positively significant with the odds ratios and 95 % confidence intervals of odds ratios (2.96; 1.396-6.279), (2.59; 1.460-4.607), (3.13; 1.325-7.394), (10.6; 7.007-15.941), (2.11; 1.364-3.269) and (2.08; 1.309-3.305), respectively. While the three factors including lifestyle, fluid consumption and use of fruits are found to be negatively significant with odds ratios and 95% confidence intervals for the odds ratios (0.102; 0.056-0.187), (0.268; 0.183-0.392) and (0.292; 0.193-0.440), respectively indicating that these three factors are protective factors against urinary bladder cancer. In area wise study, eight factors age, social status, lifestyle, family history, cigarette smoking, tea, fluid consumptions and iv fruits in Punjab, three factors cigarette smoking, source of drinking water and fried items in Islamabad, six factors chemical exposure, lifestyle, cigarette smoking, fluid consumption, fried items and fruit in Khyber Pukhtoon Khwa, three factors cigarette smoking, fluid consumption and fruits in Baluchistan and two factors cigarette smoking and fluid consumption in Sindh are found to be significant. In eight factors of Punjab, age, family history, cigarette smoking and tea are found to be positively significant while the other four factors social status, lifestyle, fluid consumptions and fruits are negatively associated with the bladder cancer. In three factors of Islamabad, two factors cigarette smoking and fried items are observed to be positively significant while the source of drinking water (government provided water) is observed to be protective as compared to the tap water. In six factors of Khyber Pukhtoon Khwa, chemical exposure, cigarette smoking and fried items are directly associated with the risk of bladder cancer while the other three factors lifestyle, fluid consumption and fruit are the protective factors for the disease. In three factors of Baluchistan, cigarette smoking is found to be positively significant while the fluid consumption and fruits are inversely associated with risk of bladder cancer. In two factors of Sindh, cigarette smoking is directly associated with disease while the other fluid consumption is found to be negatively significant. Cigarette smoking is the major risk factor and found to be significant in each area of Pakistan. Fluid consumption is also major protective factor and found to be significant in all areas except Islamabad. In studying the occupational risk factors, four categories of the occupations including cooks, drivers, metal workers and textile workers are found to be significant with the odds ratios and the 95% confidence intervals (14.132; 4.068 - 49.088), (7.949; 3.321- 19.025), (7.571; 3.147 - 18.214) and (2.168; 1.136 - 4.138), respectively. While the farmers, painters and leather workers are observed to be insignificant in Pakistan. According to this study, the cooks are at higher risk of bladder cancer as compared to all other occupations. Key Terms: Bladder cancer, Risk Factors, Logistic Regression, Odds ratio, Controls, Significance, Retrospective v CONTENTS Acknowledgement i Abstract iii Abbreviations ix List of Tables xi List of Figures xii CHAPTER 1 INTRODUCTION 1 1.1 Medical Terms 1 1.2 Statistical /General Terminology 5 1.3 Cancer 6 1.3.1 Direct spread 7 1.3.2 Spread through blood 7 1.3.3 Spread through the lymphatic system 8 1.3.4 Epidemiology of Cancer 8 1.4 Urinary Bladder Cancer 9 1.4.1 Main Types of Urinary Bladder Cancer 9 1.4.2