Sir Richard Doll (19122005), Physician, Epidemiologist, Teacher, Humanitarian, Legend, Activist, Researcher, Public Health lobbyist Smoking and Health CONDITIONS TREATED WITH TOBACCO 16th Century Cough Gout Asthma Diseases of women Headaches Intestinal worms Stomach cramps Open wounds Malignant tumours SÖMMERING 1795 DOCTORAL THESIS “Carcinoma of the lip is most frequent when people indulge in tobacco pipes. For the lower lip is particularly attacked by carcinoma because it is compressed between the pipe and the teeth” PERCENTAGE OF MEN ATTENDING MASSACHUSETTS CANCER CLINICS WITH DIFFERENT CANCERS: BY SMOKING HABIT (Potter & Tulley, 1945) Use of tobacco (no. of men) None (655) Slight (357) Moderate (1155) Excessive (760) Cancer of: buccal cavity 3.7 8.1 11.5 17.9 respiratory tract 0.5 1.1 2.0 1.7 other sites 22.4 25.1 26.0 23.4 USE OF TOBACCO BY DISEASE CATEGORY: 86 MEN WITH AND 86 MEN WITHOUT LUNG CANCER (after Müller, 1939) Type of smoker No. of men with lung cancer 1Extreme 2Very smoker 25 4 heavy smoker 18 5 13 22 27 41 3 14 3Heavy smoker 4Moderate smoker Non-smoker 1 10-15 2 7-9 3 4-6 4 1-3 healthy controls cigars, >35 cigarettes, >50g pipe tobacco/day “ 26-35 “ 36-50g “ “ “ “ 16-25 “ 21-35g “ “ “ “ 1-15 “ 1-20g “ “ “ SMOKING AND LUNG CANCER CASE-CONTROL STUDIES BEFORE 1950 Author No. of men Lung Controls cancer Percent of: Non-smokers Heavy smokers Lung Controls cancer Lung Controls cancer Müller, 1939 Germany 36 86 3.5 16.3 65 36 Schairer & Schöniger, 1943 Germany 93 270 3.2 15.9 52 27 134 100 4.5 19.0 55 19 Wassink, 1948 Holland TOBACCO AND CORONARY DISEASE (English, Willius & Berkson, 1940) Men aged (yrs) Percent smokers Coronary Others disease 40-9 50-9 60+ 79.7 (149/187)† 71.7 (274/382) 63.8 (275/431) 40+ 69.8 (698/1000) 66.3 (663/1000) 61.9 (187/302) 73.9 (274/371) 61.8 (202/327) P* <0.001 ─ 0.28 0.05 *P, one-sided †Number of smokers and all men in age group in parentheses TOBACCO AND CORONARY DISEASE (English, Willius & Berkson, 1940) Men aged (yrs) Percent coronary disease in: P* Smokers Non-smokers 40-9 50-9 60+ 4.8 (10/208)† 6.2 (24/388) 5.0 (20/404) 1.0 (2/208) 2.6 (10/388) 6.4 (26/404) 0.01 0.01 ─ 40+ 5.4 (54/1000) 3.8 (38/1000) 0.04 *P, one-sided †Number of men with coronary disease and all diseases in age group in parentheses SMOKING AND LUNG CANCER CASE-CONTROL STUDIES PUBLISHED IN 1950 Author No. of men Lung Controls cancer Percent of: Non-smokers Heavy smokers Lung Controls Lung Controls cancer cancer 82 522 14.6 23.9 18 9 236 481 15.3 21.7 ─ ─ 444 430 7 31 ─ ─ Wynder & Graham 605 USA 780 1.3* 14.6* 51 19 649 649 0.3* 4.2* 26 13 Schreck et al. USA Levin et al. USA Mills & Porter USA Doll & Hill UK *Lifelong non-smokers, with ex-smokers carefully excluded MORTALITY BY AMOUNT SMOKED RELATIVE TO THAT IN NON-SMOKERS (after Hammond & Horn, 1954) Age (yrs) No. of deaths Regular cigarette smokers smoking (per day): 20 Less than 10-19 or more 10 50-69 167 50-54 377 1.7 2.1 2.5 55-59 571 1.1 1.9 2.1 60-64 594 1.5 2.2 2.0 65-69 605 1.0 1.3 1.1 42 8.8 Cause of death lung cancer coronary heart disease BERKSON’S ALTERNATIVES “The findings were the result of the interplay of various subtle and complicated biases or had a constitutional basis, involving people who were non-smokers or relatively light smokers, being the kind who were biologically selfprotective and this “correlated with robustness in meeting mortal stress from disease generally” FISHER’S OBJECTIONS (i) Smokers with lung cancer reported inhaling less than smokers without (Doll & Hill, 1950) against causation unless it was concluded that “Inhaling cigarette smoke was a practice of considerable prophylactic value in preventing the disease” FISHER’S OBJECTIONS (ii) Secular changes in smoking habits could not be related to the increase in lung cancer since “lung cancer has been increasing more rapidly in men relative to women” while “it is notorious, and conspicuous in the memory of most of us, that over the last 50 years the increase among women has been great, and that the increase among men (even if positive) certainly small” CANCERS CAUSED IN PART BY SMOKING (International Agency for Research on Cancer, 2004) Bladder *Lung Cervix Myeloid leukaemia Nasopharynx Kidney Oral (incl. lip & tongue) *Oro- & hypopharynx Pancreas *Larynx Nose & nasal sinuses Stomach Liver *Oesophagus Ureter *Increased more than fivefold VASCULAR AND RESPIRATORY DISEASE CAUSED IN PART BY SMOKING *Pulmonary heart disease Subarachnoid haemorrhage Ischaemic heart disease Cerebral thrombosis Myocardial degeneration Cerebral haemorrhage Hypertension (fatal) *Chronic obstructive lung disease Arteriosclerosis Pneumonia *Aortic aneurysm Asthma *Peripheral vascular disease Pulmonary tuberculosis *Buerger’s disease *Increased more than five-fold OTHER CONDITIONS CAUSED IN PART BY SMOKING Gastric ulcer Duodenal ulcer Periodontitis *Tobacco amblyopia Crohn’s disease Age-related macular degeneration Osteoporosis Cataract Reduced fecundity Facial skin wrinkling Reduced growth of fetus *Palmoplantar pustulosis *Increased more than five-fold UK male doctors born 1900-1930: continuing cigarette vs never smokers. 50-year follow-up of mortality, 1951-2001 Evaluation