Sir Richard Doll (1912-2005), Physician,

Epidemiologist, Teacher, Humanitarian, Legend,

Activist, Researcher, Public Health lobbyist

Smoking and Health

CONDITIONSTREATED WITH TOBACCO

16th Century

Malignant tumours

Open woundsStomach cramps

Intestinal wormsHeadaches

Diseases of womenAsthma

GoutCough

SÖMMERING 1795DOCTORAL 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 ATTENDINGMASSACHUSETTS CANCER CLINICS

WITH DIFFERENT CANCERS: BY SMOKING HABIT(Potter & Tulley, 1945)

Use of tobacco(no. of men)

Cancer of:

buccalcavity

respiratorytract

othersites

None (655) 3.7 0.5 22.4

Slight (357) 8.1 1.1 25.1

Moderate (1155) 11.5 2.0 26.0

Excessive (760) 17.9 1.7 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

withlung cancer

healthycontrols

1Extreme smoker 25 42Very heavy smoker 18 53Heavy smoker 13 224Moderate smoker 27 41

Non-smoker 3 14

1 10-15 cigars, >35 cigarettes, >50g pipe tobacco/day2 7-9 “ 26-35 “ 36-50g “ “ “3 4-6 “ 16-25 “ 21-35g “ “ “4 1-3 “ 1-15 “ 1-20g “ “ “

SMOKING AND LUNG CANCERCASE-CONTROL STUDIES BEFORE 1950

195519.04.5100134Wassink, 1948Holland

275215.93.227093Schairer &Schöniger, 1943Germany

366516.33.58636Müller, 1939Germany

ControlsLungcancer

ControlsLungcancer

Heavy smokersNon-smokersControlsLungcancer

Percent of:No. of menAuthor

TOBACCO AND CORONARY DISEASE(English, Willius & Berkson, 1940)

†Number of smokers and all men in age group in parentheses

*P, one-sided

0.0566.3 (663/1000)69.8 (698/1000)40+

0.2861.8 (202/327)63.8 (275/431)60+

─73.9 (274/371)71.7 (274/382)50-9

<0.00161.9 (187/302)79.7 (149/187)†40-9

Others Coronary disease

P*Percent smokersMen aged(yrs)

TOBACCO AND CORONARY DISEASE(English, Willius & Berkson, 1940)

†Number of men with coronary disease and all diseases in age group in parentheses

*P, one-sided

0.043.8 (38/1000)5.4 (54/1000)40+

─ 6.4 (26/404)5.0 (20/404)60+

0.012.6 (10/388)6.2 (24/388)50-9

0.011.0 (2/208)4.8 (10/208)†40-9

Non-smokers Smokers

P*Percent coronary disease in:Men aged(yrs)

SMOKING AND LUNG CANCERCASE-CONTROL STUDIES PUBLISHED IN 1950

195114.6*1.3*780605Wynder & GrahamUSA

──317430444Mills & PorterUSA

*Lifelong non-smokers, with ex-smokers carefully excluded

13264.2*0.3*649649Doll & HillUK

──21.715.3481236Levin et al.USA

91823.914.652282Schreck et al.USA

ControlsLungcancer

ControlsLungcancer

Heavy smokersNon-smokersControls

Lungcancer

Percent of:No. of menAuthor

MORTALITY BY AMOUNT SMOKEDRELATIVE TO THAT IN NON-SMOKERS

(after Hammond & Horn, 1954)

1.11.31.060565-69

2.02.21.559460-64

coronary heart disease

2.11.91.157155-59

2.52.11.737750-54

lung cancer8.84216750-69

20or more

10-19Less than10

Cause ofdeath

Regular cigarette smokerssmoking (per day):

No. ofdeaths

Age(yrs)

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 self-protective 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)

*Increased more than fivefold

Ureter*Oesophagus Liver

Stomach Nose & nasal sinuses

*Larynx

Pancreas Nasopharynx Kidney

*Oro- & hypo- pharynx

Myeloid leukaemia

Cervix

Oral (incl. lip & tongue)

*Lung Bladder

VASCULAR AND RESPIRATORY DISEASECAUSED IN PART BY SMOKING

*Increased more than five-fold

*Buerger’s disease

Pulmonary tuberculosis*Peripheral vascular disease

Asthma*Aortic aneurysm

Pneumonia Arteriosclerosis

*Chronic obstructive lung disease Hypertension (fatal)

Cerebral haemorrhage Myocardial degeneration

Cerebral thrombosis Ischaemic heart disease

Subarachnoid haemorrhage*Pulmonary heart disease

OTHER CONDITIONSCAUSED IN PART BY SMOKING

*Increased more than five-fold

*Palmoplantar pustulosisReduced growth of fetus

Facial skin wrinklingReduced fecundity

CataractOsteoporosis

Age-related macular degenerationCrohn’s disease

*Tobacco amblyopiaDuodenal ulcer

PeriodontitisGastric ulcer

UK male doctors born 1900-1930: continuing cigarette vsnever smokers. 50-year follow-up of mortality, 1951-2001