Epigenetic basis of cancer health disparities: Looking beyond genetic differences

Abstract

Despite efforts at various levels, racial health disparities still exist in cancer patients. These inequalities in incidence and/or clinical outcome can only be explained by a multitude of factors, with genetic basis being one of them. Several investigations have provided convincing evidence to support epigenetic regulation of cancer-associated genes, which results in the differential transcriptome and proteome, and may be linked to a pre-disposition of individuals of certain race/ethnicity to early or more aggressive cancers. Recent technological advancements and the ability to quickly analyze whole genome have aided in these efforts, and owing to their relatively easy detection, methylation events are much well-characterized, than the acetylation events, across human populations. The early trend of investigating a pre-determined set of genes for differential epigenetic regulation is paving way for more unbiased screening. This review summarizes our current understanding of the epigenetic events that have been tied to the racial differences in cancer incidence and mortality. A better understanding of the epigenetics of racial diversity holds promise for the design and execution of novel strategies targeting the human epigenome for reducing the disparity gaps.

Racial health disparities in ovarian cancer: not just black and white

“…Interestingly, PSPHL levels are relatively higher in AA breast tumors than the CA breast tumors [ 33 ]. Health disparities in breast cancer are well documented [ 34 , 35 ] and the study on PSPHL in breast tumors [ 33 ] identified partial deletion (30Kb long fragment) of chromosome 7p11 in CA women, which led to attenuation of expression of PSPHL in CA breast tumors. No such mechanism was proposed for observed disparate expression of PSPHL in OCs of AA vs. CA origin, and would be interesting to elucidate.…”

“…Epigenetic changes are known to function as liaisons between socioeconomic factors and the genome; they keep accumulating and affecting the epigenome in various racial/ethnic groups, resulting in disparate and poor cancer outcomes [ 35 ]. A functional role of epigenetic changes in aggressive high-grade serous OC has been described, leading to resistance against platinum-containing chemotherapy [ 53 ].…”

“…As mentioned above, endometrial cancers and OCs belong to the same family of gynecological cancers. Incidentally, there is evidence in the literature suggesting an epigenetic basis of health disparity in endometrial cancers [ 35 ], particularly, differential ribosomal DNA methylation in AA vs. CA patients [ 54 ]. This raises the hope that the differential methylation, as observed in drug-resistant OCs [ 53 ] might also be relevant in OC health disparity.…”

Pan‐cancer clinical and molecular analysis of racial disparities

“…10 In addition, AA patients with breast, head and neck, or endometrial cancer have higher levels of chromosomal instability and frequency of TP53 mutations and CCNE1 amplification than white patients. 17 Furthermore, race is a social construct and is often a proxy for chronic stressors that minority populations face, such as low socioeconomic status, Cancer February 15, 2020 poor access to health care, dangerous environments, and interpersonal discrimination. 15,16 Epigenetic differences are particularly relevant because they can be shaped by environmental factors, such as chronic stress, social interactions, and toxins.…”

“…15 Theses epigenetic changes can function as a liaison between social, cultural, and environment factors and the genome. 17 Furthermore, race is a social construct and is often a proxy for chronic stressors that minority populations face, such as low socioeconomic status, Cancer February 15, 2020 poor access to health care, dangerous environments, and interpersonal discrimination. 18 These unique stressors that a racial group experiences may affect their epigenome and ability to respond to disease, leading to poor outcome and response to therapy.…”