Gene expression and ethnicity: Does it matter?
Last Updated on December 23, 2017 by Joseph Gut – thasso
December 05, 2017 – We are entering the age of precision medicine, in which diagnosis and therapy decisions for each patient will be based on detailed genetic and molecular fingerprints. Unfortunately, much of the revolutionary work that underpins precision medicine has been conducted on populations of European (Caucasian) descent, with limited amount of work in populations of different ethnic backgrounds.
There is, however, mounting evidence that ethnicity might play a role in several aspects when it comes to the genetic and molecular ethology of clinical phenotypes (i.e., representations of diseases). Thus, on one hand, the prevalence of particular disease causing allelic variants of genes may considerably be different going from one ethnicity to another. On the other hand, the underlying genetic aberrations, mutations, or risk loci which give rise to apparently the same clinical phenotype (i.e., manifestation of a disease) across individuals of different ethnic descent may be very different.
Even the expression of genes, irrespective of disease-underlying mutations and aberrations, may differ between ethnicities in association with the same clinical phenotype. Thus, recent research has revealed that differences in the genes expressed in non-small cell lung cancer (NSCLC) from some African-Americans and European (Caucasian)-Americans exist, suggesting that there are ethnic differences in the biology of NSCLC, which could have clinical relevance and possibly also influence therapy options and decisions.
A research team analyzed normal and NSCLC tissue obtained from 64 African-Americans and 74 European (Caucasian)-Americans during surgery to remove their lung tumors. Tissue from 22 African-Americans and 19 European (Caucasian)-Americans was analyzed for mRNA expression, which provides information about gene expression, and tissue from the remaining patients was analyzed for microRNA expression. These two different kinds of RNA have related, but different, roles inside the cell. The researchers found that expression of 2,210 genes was more than two-fold increased or decreased in NSCLC from African-Americans compared with matched normal tissue. For European (Caucasian)-American samples, 2,921 genes were differentially expressed by more than two-fold. Many of the genes were differentially expressed between NSCLC and normal tissue in both African-Americans and European (Caucasian)-Americans, but 637 and 1,844 were differentially expressed only in African-Americans and European (Caucasian)-Americans, respectively.
The genes differentially expressed only in the African-American NSCLC samples were enriched for those involved in stem cell biology and invasive behavior. The genes differentially expressed only in European (Caucasian)-Americans were enriched for those involved in cell cycle, mitosis, and proliferation. In addition, the genes differentially expressed only in African-Americans or European (Caucasian)-Americans were analyzed using a drug-response prediction model called the Connectivity Map (CMAP). The two gene subsets predicted similar resistance/sensitivity for NSCLC from African- Americans and European (Caucasian)-Americans to some drugs. For other drugs, the predictions varied by ethnicity, with NSCLC from African-Americans predicted to be resistant to 53 drugs to which NSCLC from European (Caucasian)-Americans was sensitive. Among these drugs was Irinotecan, which is a cytotoxic chemotherapeutic used for treating certain types of cancer.
This study helps close an important gap in the knowledge of which genes are specifically expressed in lung cancers from African-Americans, revealing clear differences in lung cancer biology between African- Americans and European (Caucasian)-Americans. Understanding these ethnic differences in gene expression may ultimately help to reduce some health outcome disparities between members of different ethnic groups. These kind of studies need to be replicated in still larger cohorts of patients and, obviously, to other ethnicities as well in order to forward precision medicine analyses to not only lung cancer patients, but also to patients suffering from any other disease, in minority populations.