Early onset lung cancer: Racial differences in familial aggregation, genetic polymorphisms and survival.

Abstract

In the United States in 2004 it is estimated that lung cancer will be responsible for more than one quarter of all cancer-associated deaths. With an overall 5-year survival of less than 15%, lung cancer is one of the most rapidly fatal common malignancies diagnosed. Since 1973, prognosis and survival has remained nearly constant. Differences in incidence of lung cancer and survival after diagnosis vary significantly by race. African Americans, particularly men, are at greater risk for development of lung cancer and tend to have poorer survival than their Caucasian counterparts. Cigarette smoking is an established risk factor for lung cancer. However, only 10% to 15% of smokers develop lung cancer, and cases occur among nonsmokers. This suggests that there are individual susceptibilities to environmental carcinogens which may have a genetic basis. Three studies were conducted in young lung cancer cases identified from a population-based cancer registry in metropolitan Detroit. The first study examined aggregation of lung cancer in family members of lung cancer cases compared to families of population-based controls. The second study, a case control study, evaluated lung cancer risk associated with polymorphisms in glutathione S-transferase genes (<italic>GST</italic>s). The third study, a case-only study, evaluated lung cancer survival associated with polymorphisms in <italic>GST</italic>s. Familial aggregation of lung cancer was demonstrated in families of young cases, with risk of lung cancer higher in African American families than Caucasian families. Overall, individuals who carried combinations of <italic>GST</italic> polymorphisms that result in low enzyme expression were at increased risk of having lung cancer compared to individuals with fully functional genes. This increase in risk was especially apparent in Caucasian heavy smokers and among all African Americans. Among late stage, non-small cell lung cancer cases who received chemotherapy, decreased survival time was seen in those with combinations of dysfunctional <italic>GST</italic> genes. Collectively, these results support a genetic component of lung cancer development and survival in young onset cases. Further characterization of high risk individuals is necessary for health practitioners to tailor risk reduction and treatment protocols to the populations they serve.