Interactions among genes, tumor biology and the environment in cancer health disparities: examining the evidence on a national and global scale

Abstract

Cancer incidence and mortality rates show great variations across nations and between population groups. These variations are largely explained by differences in age distribution, diet and lifestyle, access to health care, cultural barriers and exposure to carcinogens and pathogens. Cancers caused by infections are significantly more common in developing than developed countries, and they overproportionally affect immigrant populations in the USA and other countries. The global pattern of cancer is not stagnant. Instead, it is dynamic because of fluctuations in the age distribution of populations, improvements in cancer prevention and early detection in affluent countries and rapid changes in diet and lifestyle in parts of the world. For example, increased smoking rates have caused tobacco-induced cancers to rise in various Asian countries, whereas reduced smoking rates have caused these cancers to plateau or even begin to decline in Western Europe and North America. Some population groups experience a disproportionally high cancer burden. In the USA and the Caribbean, cancer incidence and mortality rates are excessively high in populations of African ancestry when compared with other population groups. The causes of this disparity are multifaceted and may include tumor biological and genetic factors and their interaction with the environment. In this review, we will discuss the magnitude and causes of global cancer health disparities and will, with a focus on African-Americans and selected cancer sites, evaluate the evidence that genetic and tumor biological factors contribute to existing cancer incidence and outcome differences among population groups in the USA.

Fig. 1.

Inhibition of the KAI1 cancer metastasis suppressor pathway in African-American patients. KAI1 on tumor cells was shown to interact with DARC on the vascular endothelium, leading to metastasis suppression (66). Loss of DARC expression on erythrocytes, which is common in populations of African ancestry, and reduced DARC expression in tumors may compromise this metastasis suppressor pathway. Other mechanisms of KAI1 suppression include the loss of KAI1 expression, which is commonly found in many human cancers, and overexpression of the autocrine motility factor receptor (AMFR or gp78) which targets KAI1 for degradation (68). AMFR was found to be overexpressed in prostate and breast tumors of African-American patients when compared with tumors from European-American patients (54,69,70).

Fig. 2.

Potential origin and effects of the interferon-related gene signature in tumor biology. Tumor-induced mechanisms, environmental stimuli and/or ancestry-driven intrinsic factors are candidate exposures that induce the interferon-related gene signature in prostate and breast tumors. This signature may lead to poor outcome by mechanisms including EMT and increased metastatic potential, suppression of T-cell toxicity and resistance to therapy. EMT, epithelial to mesenchymal transition.

Fig. 3.

Possible disease-modifying implications of an immune signature in breast and prostate tumors of African-American patients. Differences in tumor immunobiology and in the development of a low-grade inflammation between African-American and European-American may arise from differences in either environmental or tumor environmental exposures or could be related to tumor subtype differences between the two patient groups. A low-grade chronic inflammation in tumors has been linked to activation of oncogenic pathways, increased tissue remodeling and tumor vascularization and the development of tumor immune escape mechanisms. VEGF, vascular endothelial growth factor.