Causes of cancer

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2 : Contents A ‘classic’ of public health: Doll & Peto’s “The causes of cancer” Questions for clarification and discussion: inference from measures of attribution New insights: revised estimates
3 : “The causes of cancer” Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. JNCI 1981; 66 no. 6 Indirect evidence for avoidability:- international variation- changes in incidence on migration- changes in incidence over time Direct evidence for avoidability:- table with "proportions of cancer deaths attributed to various different factors”
4 : Indirect evidence for avoidability International variation in incidence/mortality is enormous Changes in incidence/mortality on migration are substantial Changes in incidence/mortality over time are substantial
5 : Mortality from cancer of the large intestine in men
6 : Cancer incidence in Japan and in Hawaii
7 : Famous table (1) What is in it? - Population Attributable Fractions, expressed as % of all cancer deaths - “Best estimate” and “range of acceptable estimates” - Mixed bag of factors - all “extrinsic” or “environmental”
8 : Famous table (2)
9 : Famous table (3) How were these figures calculated? - epidemiological evidence - calculation of PAF for separate cancers - weighted with number of deaths to derive PAF for all cancers Main conclusions - very large proportion of all cancer deaths potentially avoidable - mainly behaviourally mediated - uncertainty is rather substantial
10 : Questions for clarification and discussion (1) Would these figures apply to cancer incidence? Would these figures apply to other countries? Do all these factors together account for appr. 95% of cancer?
11 : Questions for clarification and discussion(2) Can we conclude that only a small proportion is attributable to non-environmental, e.g. genetic, causes? Can we conclude that only a small proportion is attributable to non-behavioural factors? Do we really believe that such a high proportion is avoidable?
12 : PAF and Rothman’s general model of causation (1) “Cause” of a disease: “event, condition or characteristic that plays an essential role in producing the occurrence of the disease” “Sufficient cause” of a disease: a set of minimal events, conditions or characteristics that inevitably produce disease” (minimal: none is superfluous)
13 : PAF and Rothman’s general model of causation (2) A sufficient cause of a disease always consists of several component causes (not all smokers develop lung cancer) Most diseases will have several sufficient causes Sum of PAF’s for different component causes exceeds 100% PAF’s cannot be subtracted from 100% to derive the proportion due to other component causes
14 : Rothman’s general model of causation SUFFICIENT CAUSE SUFFICIENT CAUSE SUFFICIENT CAUSE I II III if 50% 30% 20% then PAF A 1.00 B 0.80 C 0.70 etc. ?>> 1.00 E D A B C H G A F B J I A C F
15 : Environmental vs. genetic causation Environmental and genetic causes do not compete with each other, but work together to produce disease Gene-environment interaction:- genotype may determine susceptibility to environmental determinants- environmental determinants may cause gene mutations
16 : Really avoidable? Translation of PAF into PIF assumes a causal relationship - most RR’s were estimated in observational studies - intervention studies do not show effects of the same magnitude Revised estimates (2001)- based on up-to-date evidence- removal of overlap
17 : Revised Doll & Peto table (Peto 2001)


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