Biologic risk factors

In general, all studies suggesting genetic suscepti-
bility have also shown strong risk due to cigarette
smoking and often have shown an interaction of
high-risk genotype and smoking on lung cancer
risk. When trying to determine whether a complex
disease or trait such as lung cancer has a genetic
susceptibility, one asks three major questions:
1 Does the disease (lung cancer) cluster in families?
If some risk for lung cancer is inherited, then one
would expect to see clustering of that trait in some
families above what would be expected by chance.
2 If the aggregation of lung cancer does occur in
some families, can the observation be explained by
shared environmental/cultural risk factors? In this
disease, one needs to assess whether the familial
clustering of lung cancer is solely due to clustering
of smoking behaviors or other environmental expo-
sures within families.
3 If the excess clustering in families is not explained
by measured environmental risk factors, is the pat-
tern of disease consistent with Mendelian transmis-
sion of a major gene (i.e., of transmission through
some families of a moderately high penetrance risk
allele) and can this gene(s) be localized and identi-
fied in the human genome.