Lung cancer has been shown to aggregate in families of nonsmoking lung canc
er cases with an earlier age at onset. The current study evaluates whether
relatives of nonsmoking lung cancer cases are at increased risk of cancers
at sites other than lung. Families were identified through 257 population-b
ased, nonsmoking lung cancer cases and 277 population-based, nonsmoking con
trols residing in metropolitan Detroit. Data were collected for 2,252 relat
ives of cases and 2,408 relatives of controls. First-degree relatives of no
nsmoking lung cancer cases were at 1.52-fold (95% CI, 1.02-2.27) increased
risk of cancer of the digestive system after adjustment for each relative's
age, race, sex, and smoking status. Relative risk estimates also were elev
ated, but not significantly, for tobacco-related cancers (RR = 1.39) and br
east cancer (RR = 1.72). Among first-degree relatives of younger probands (
age 40-59), risk was non-significantly increased 72% (95% CI 0.95-3.10) for
all cancers combined and 3.14-fold for cancers of the digestive system (95
% CI 0.76-12.9). Nonsmoking relatives of cases were at increased risk of al
l cancer sites combined (RR = 1.32; 95% CI 1.003-1.73), cancers other than
lung (RR = 1.37; 95% CI 1.03-1.82), and digestive system cancers (RR = 2.01
; 95% CI 1.20-3.37). These findings of moderate familial aggregation for ca
ncers of the lung, digestive system, breast, and tobacco-related sites sugg
est that common susceptibility genes may act to increase risk for a variety
of cancers in families. Genet. Epidemiol. 17:1-15, 1999. (C) 1999 Wiley-Li
ss, Inc.