Racial Differences in Cancer Susceptibility and Survival: More Than the Color of the Skin?

Abstract

Epidemiological studies point to race as a determining factor in cancer susceptibility. In US registries recording cancer incidence and survival by race (distinguishing 'black versus white'), individuals of African ancestry have a globally increased risk of malignancies compared with Caucasians and Asian Americans. Differences in socioeconomic status and health-care access play a key role. However, the lesser disease susceptibility of Hispanic populations with comparable lifestyles and socioeconomic status as African Americans (Hispanic paradox) points to the concomitant importance of genetic determinants. Here, we overview the molecular basis of racial disparity in cancer susceptibility ranging from genetic polymorphisms and cancer-driver gene mutations to obesity, chronic inflammation, and immune responses. We discuss implications for race-adapted cancer screening programs and clinical trials to reduce disparities in cancer burden.

Figure 1. Racial differences in cancer incidence and survival

Incidence (A) and 5-year survival (B) of all cancer registered cancer sites for White and Black, all ages and both sexes, confounded for the years 1975–2013 and 1975–2012, respectively. Data retrieved from SEER 2012

Figure 2. Persistence of survival disparity between Black and White over time

Despite a significant decline in incidence of head and neck squamous cell carcinoma (HNSCC) in Black men compared to White men (A) over the time period of 1975–2013, with currently even lower incidence rates among Black men, the survival disparity remains (B). In Black women the incidence (C) and survival (D) of breast cancer are both lower compared to White women. In prostate cancer, the higher incidence (E) in Black men persists, while the survival (F) differences diminish over time.

Figure 2. Persistence of survival disparity between Black and White over time

Despite a significant decline in incidence of head and neck squamous cell carcinoma (HNSCC) in Black men compared to White men (A) over the time period of 1975–2013, with currently even lower incidence rates among Black men, the survival disparity remains (B). In Black women the incidence (C) and survival (D) of breast cancer are both lower compared to White women. In prostate cancer, the higher incidence (E) in Black men persists, while the survival (F) differences diminish over time.

Figure 3. Key Figure. Biological basis of disparity in cancer susceptibility among different races

There is evidence for evolutionary selection of polymorphisms in the Th2 immune response in African populations. The prevalence of obesity in African Americans and Hispanics is significantly higher than in Caucasians and Asians. A major driver of obesity-related cancer is chronic inflammation, which is associated with an increased release of inflammatory cytokines such as TNFα, IL6, IL8, IL1-ß which results in imbalance of circulating adipose tissue cytokines or “adipokines”, such as leptin, adiponectin and hepatocyte growth factor (HGF). The racial differences in metabolism and inflammatory response contribute to differences in the immune system, how they affect cancer initiating cells and the tumor microenvironment needs to be explored. The disparity in cancer susceptibility and survival is presumably a consequence of biological and environmental factors, such as differences in life-style, risk behavior and health care access.