Increased cancer risk among relatives of nonsmoking lung cancer cases.

Lung cancer has been shown to aggregate in families of nonsmoking lung cancer 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-based, nonsmoking lung cancer cases and 277 population-based, nonsmoking controls residing in metropolitan Detroit. Data were collected for 2,252 relatives of cases and 2,408 relatives of controls. First-degree relatives of nonsmoking 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 elevated, but not significantly, for tobacco-related cancers (RR = 1.39) and breast 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 all 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 cancers of the lung, digestive system, breast, and tobacco-related sites suggest that common susceptibility genes may act to increase risk for a variety of cancers in families.