r-,"n=C ppMTqpMj=0N TO T11%. CANrPR
Tr&~vductian
-njis idea was rli--,-A in the 195o's-60's
particularly by Sir Ronald
Fisher arid Professor Philip Burch, both of wh-
are - Tt-
idea found little generals support largely becal
Sir RIChard Doll
claim-d epidemiology demonstrated that
enVirCFM*Mt:al carcinogens,
including tcba -*-*e, were responsible for nearly
all cancer deaths.
Durang August 1990, five scientIfIC papers and one
c=iference. presentation
(U.I.C.C. Cancer Meeting, Hmd=g, August 1990) have
zdli~ -z--A the genetic
issa either directly or indirectly, (but not
independen~tly of
envIramental risk factors). Furthermore one of the
scientific papers is
F a group in the USA (Caporaso and colleagues)
iwtm are clow to a group
supported by the BAT SC3.MTUflC Res-rch Q-V (Idle
and colleagues,
umversity of Newcastle) utu-je another paper by
sellers and colleagues is
partly sL4*crted by the Council for Tobacco
Research USA.
r-wents on P-s
The paper by Sellers (Evidence for Mendelian
InIx--ritance. In the
Patingenesis of iurq cancer) addresses the
broadest.iss . It is based
on the use of the segr~aticn Analysis, a rare - -
I i -t stat! --t-ical
technique that is currently being examined by one
of ct= cotisultants.
Further comments on the validity or cthexwise of
t1iis statistical
technique will be --- in due course, although it
does appea to ccnfl3.ct
in some ways with the age-distribution analysis
w=,ch was so mx:h a
feature of BLmch's work. However, as published,
the clai made by
sellers are quite startling, and are based on an
age x genetic x --ok~
interaction analysis. Miere are three genetic
variants (genotypes):
AA Susceptible
AB Partly Susceptible
BB Not Susceptible.
?ie following matrix of relative risk v. age,
snciang status and gerx)t-ype
is given in the paper.
Tobacco Relative Risk* (Genotype)
Age T-~~ Tre of DeveloDi,= I-= Cancer
AA AB BB
50 0 2246 15 1
Average (A) 327 14 1
Heavy (H) 63 12 1
60 0 618 14 1
A 56 12 1
H U 7 1
70 0 112 13 1
A 10 6 1
H 3 2 1
Unfortunately this table is misleading becalne for
each horizontal
line- the risk is only catpared to the BB gene=
group. It is not,
therefore, an absolute measure of the chance of
getting lung cancer -
merely the risk relative to the BB Group. Far more
70 year olds the
of lung cancer than do 50 year olds
(-n
CD
ON
BATCo document for Province of BritiSh Columbia 26
October 1999


:--ually, the figures do not mean that 2246
rion-smokers die relat-,ve to 63
2 neavy mokers (lines I and 3).
:t is clairm in the paper that AA smokers have a
27.2% prcbability of
~evelcping lung cancer by age 50, this probability
app--tly rot
:..-=%siM greatly with age, and it can be
calculated from the that
:f the non-smokers who die by age 50, the vast
majority are of the AA
c disposition:
2246 99.3%
2245+15+1
ziowever, the analysis gives swklrxj an ever
increasing role with age,
?mwtic prpAi-p-itian being clai-d to be less
important for old persons
rid, for heavy smokers age 70, it is claimed only
W% are of the AA
- type-
-11ers is not able to identify the nature of the
genetic variation but
scme scientists believe it to be associated with
matatiorr. on a specific
gene (CYP2D6), active in the metabolism of drugs
and potmmial
inogens, and the err-losed editorial by Bonney
diso this. Cne
of this gene is respcnsible for metabolising a
drug, debrisogiine,
;md genetic variations can be identified by
follcw-Ing the metabolism of
:tis drug. niis is Professor Idle's view, although
it seems more likely
=at this is just a marker for saw closely related
gene of greater
:mDartance, such as the adjacent CYPlA1 gene known
to be ar-slot in
lung cancer cases.
~~11-,icn
~Lile nothing definitive has yet emerged Fr -n
this area and the present
pape is clearly speculative, it will nevertheless
provoke =xh further
and it is irpexative to monitor the Scientific
FdrAarch as it
z ones. If genetic predisposition is subsequently
validated for lung
-=er and other major disea , the implications for
Society in
people at risk could be enormous. Mus
idert-ificat-cn could
achieved within the rmct 5-10 years.
R.E. Thornton
=/SC
=11 September, 1990
Un
CD
N;
N.;
BATCO document for Province of BritiSh Columbia 26
October 1999