Effect of cohort differences in smoking prevalence on models of lung cancer susceptibility.
Data on 337 lung cancer families were analyzed to determine if known cohort differences in parental cigarette consumption influence parameters from a segregation analysis. Previous results suggested that, after allowing for an individual's pack-years of tobacco exposure, Mendelian codominant inheritance of an allele that produced an earlier age of onset provided a good fit to the data. In the present study, the data were split into two groups of families: probands age 60 and over (born before WWI) and probands younger than age 60. This partition of the data by age of the proband was done to separate families in which there were parents who were less likely to smoke from those with parents more likely to smoke--predicated on the known increase of smoking prevalence after World War I. For the younger proband families (those with parents more likely to smoke), only Mendelian codominant inheritance adequately fit the data. The hypotheses of no major type, environmental transmission, and Mendelian dominant or recessive inheritance were rejected. In contrast to our earlier findings, the estimate of population susceptibility increased from 28% in the total data to 60% in this subset. In the older proband families (those with parents less likely to smoke), the no major type and environmental hypotheses were rejected; further, none of the Mendelian models could be distinguished. Our results demonstrate that cohort differences, probably in exposure to tobacco, can confound parameters of a segregation analysis, and suggest that the genetic component of lung cancer may be greater than previously estimated. It further suggests that susceptibility to lung cancer occurs as a function of susceptibility to the effects of tobacco smoking.
Sellers
T A
TA
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454.
Bailey-Wilson
J E
JE
Potter
J D
JD
Rich
S S
SS
Rothschild
H
H
Elston
R C
RC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D008145:Louisiana / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015995:Prevalence; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D044465:White People / Q000235:genetics