Abstract IA02: Genetic, environmental, and biological contributions to racial disparities in lung cancer incidence

Abstract

Abstract Lung cancer is the leading cause of cancer-related deaths in the United States (1). In addition, there are significant disparities in lung cancer across populations. Compared with European Americans, African Americans are disproportionally affected by lung cancer, both in terms of incidence and survival (2,3). Lung adenocarcinoma among African Americans is 1.30 (1.10 - 1.90) times higher compared with European Americans; squamous cell carcinoma 1.80 (95% C.I. 1.1 - 2.3) times higher (4). There are also differences in lung cancer outcomes between European Americans and African Americans (2,5), some of which may be due to differences in cell biology between these two populations. However, studies have generally shown that differences in access to care may explain most of the variance in survival times (5-7). In addition, the gains in survival over the past 20 years among lung cancer patients have been similar in both European Americans and African Americans. Thus, the causal factors – genetic, environmental or otherwise – that lead to a greater incidence of lung cancer in African Americans are largely unknown. Smoking is the strongest risk factor for lung cancer development. However, several studies suggest that smoking prevalence and behaviors do not fully explain the disparity in lung cancer incidence. For example, African Americans have a lower smoking prevalence than European Americans and only 5.8% of African Americans are heavy smokers, compared with 19.2% of European Americans (8). In fact, when one compares smoking rates across ethnic groups matched for equal levels of smoking, African Americans still experience a higher burden of lung cancer incidence (8) - although this is attenuated with higher numbers of cigarettes smoked per day. This has led some to suggest that African Americans are more susceptible to the carcinogenic effects of tobacco at lower doses. However, this has not been empirically tested. It is possible that there are differences in nicotine and tobacco carcinogen metabolism between European Americans and European Americans that could account for the differences in cancer incidence between. On average, 72% of nicotine is converted to cotinine, the primary proximate metabolite of nicotine (9). Racial and ethnic differences in urinary (10,11) and blood cotinine (11-13) concentration per cigarette smoked have been well established. In addition, studies have found that levels of NNK metabolites (11,14) and thiocyanate (11) are higher in African Americans compared with European Americans. However, no clear genes or pathways have yet been identified that explain the disparity. And, given the strong relationship between smoking and lung cancer, it is hard to completely discount smoking as a cause of incidence disparities (8). Other risk factors to explain higher lung cancer incidence among African Americans include genetics, SES, smoking, BMI, and/or alcohol consumption. Recent studies show that the same loci associated with risk of lung cancer in European American smokers, i.e., chr15q25, are also associated with lung cancer in African Americans (15-18). Disparities in lung cancer incidence could be driven by the environment. For example, a recent study found that African Americans were more likely to reside in areas with the highest levels of air toxin exposure (19). Studies of breast and prostate cancer (20,21) have shown that whatever the cause of cancer health disparities, the consequences of these disparities manifest themselves as differences in the molecular and cell biology of the cancer. In lung cancer, we have explored the biological differences between lung cancer in European Americans and African Americans. These studies show that while some of the perturbed pathways in lung cancer remain the same for European Americans and African Americans, there are specific differences distinct to African Americans. Continued research efforts in the field are needed to determine the contribution of smoking, and indeed other factors, to lung cancer disparities. This work needs to be complemented with research that dissects the consequences of these disparities and the translation of these discoveries into improved patient care.