Session #6: Population Diversity in Lung Tumor Biology in the United States

Worldwide, lung cancer remains the most commonly diagnosed cancer and the leading cause of cancer-related death. According to the most recent GLOBOCAN report, it accounts for 12% of all cancers in men and women, and 1 in 5 of all cancer-related deaths. Despite decades of evidence-based policy and cancer control strategies, the global burden of lung cancer remains significant, and in some countries, is rising. There are clear geographic differences in both lung cancer incidence and mortality. Lung cancer rates vary more than 20-fold across geographic regions, something that largely reflects the historical temporality of the tobacco epidemic and differences in patterns of tobacco exposure, including intensity and duration of smoking, type of cigarettes used, and smoking topography. Germline genetic differences in genes involved in nicotine metabolism, including CYP2A6, also contribute to these trends. Since public health records began tracking differences in lung cancer incidence and mortality by racial and ethnic groups within the U.S., disparities between European Americans (EAs) and African Americans (AAs) have also been identified. Specifically, lung cancer incidence is higher in AAs, especially among men. AAs also have the highest mortality rate and the lowest 5-year survival rate compared with other racial and ethnic groups. The factors contributing to this health disparity are multifactorial. For example, access to high quality health care is an important factor in lung cancer outcomes. In terms of incidence, it is likely that tobacco plays a role in the observed differences given that it is the leading etiological exposure associated with lung cancer development. However, AAs have a lower tobacco consumption overall compared with EAs and data show that the difference in lung cancer incidence persists at equal categories of cigarettes smoked per day. This suggests a divergence in the etiology of lung cancer in the U.S. between racial and ethnic groups. As the etiology of lung cancer is closely linked with both its histological presentation and molecular features, it is possible that such differences in disease etiology could be reflected at the genomic level. This molecular classification of tumors is important for understanding both a patient’s prognosis and likelihood of response to targeted therapies and, as such, is tightly linked to both survival and mortality patterns. Our current understanding of lung cancer biology is primarily derived from populations of European descent. Given the persistent disparities that exist in lung cancer incidence and survival between AAs and EAs, it is important to characterize tumor biology across racial and ethnic groups. Over the past number of years, our group has been focused on characterizing the genomic landscape of lung cancer from AAs. We find that while most tumor biology is shared between EAs and AAs, significant differences are found, including somatic mutations, somatic copy number changes, and indeed at the transcriptomic level. These data emphasize the complexity of tumor biology specifically in lung cancers from AAs and highlight new potential targets for lung cancer treatment