According to Clinical Cancer Research, a journal of the American Association for Cancer Research, recently discovered genetic differences in non-small cell lung cancers (NSCLCs) between some African-Americans and European-Americans suggest that there are racial differences in the biology of the disease. These findings could have a clinical impact on personalized cancer therapies in the future.
“We are entering the age of ‘precision medicine’ in which diagnosis and therapy decisions for each cancer patient will be based on detailed molecular and chemical fingerprints,” said researcher Bríd M. Ryan, a researcher at the National Cancer Institute’s Center for Cancer Research and the study’s author.
“Much of the revolutionary work that underpins precision medicine has been conducted on populations of European descent, with limited work in minority populations,” she added. “We want to make sure that all populations can benefit from this approach. Studying the biology of lung cancer in African-Americans is one step toward that goal.”
Dr. Ryan and her team analyzed normal and NSCLC tissue obtained from 64 African-Americans and 74 European-Americans. Tissue from 22 African-Americans and 19 European-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-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-Americans, but 637 and 1,844 were differentially expressed only in African-Americans and European-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-Americans were enriched for those involved in cell cycle, mitosis, and proliferation.
In addition, the genes differentially expressed only in African-Americans or European-Americans were analyzed using a drug-response prediction model. The two gene subsets predicted similar resistance/sensitivity for NSCLC from African-Americans and European-Americans to some drugs. For other drugs, the predictions varied by race, with NSCLC from African-Americans predicted to be resistant to 53 drugs to which NSCLC from European-Americans was sensitive. Among these drugs was irinotecan, used for treating certain types of cancer.
“This study helps close a gap in our knowledge of which genes are expressed in lung cancers from African-Americans, revealing clear differences in lung cancer biology between African- Americans and European-Americans,” said Mitchell. “By understanding these racial differences in gene expression, we can account for how they may contribute to disease progression and treatment response and, ultimately, help reduce some health outcome disparities.”
The study parallels a recent publication in Theranostics, one of whose authors is NFCR-sponsored scientist, Dr. Wei Zhang, of Wake Forest Baptist Medical Center. That team’s precision oncology study of racial differences in genetic alterations in smoking-related cancers revealed that African-Americans had a significantly increased mutation rate in the TP53 gene (tumor suppressor gene), and five genes were significantly amplified in this population. The researchers also found that a number of genes—including those that repair DNA damage—mutated at higher frequencies in African-American cancer patients versus European-Americans.
Dr. Zhang stated, “These results provide strong evidence that genomic instability is a fundamental hallmark of cancer, and the events underlying the regulation of genome stability are centered on interactions with environmental factors and lifestyle, such as smoking.”
Too, the study points to genetic mutations common to African-Americans as a factor contributing to cancer outcome disparities. This latter discovery may lead to the development of novel diagnostic and improved therapeutic options for patients.
Kytola V, Topaloglu U, Miller LD, Bitting RL, Goodman MM, D`Agostino RB Jr, Desnoyers RJ, Albright C, Yacoub G, Qasem SA, DeYoung B, Thorsson V, Shmulevich I, Yang M, Shcherban A, Pagni M, Liu L, Nykter M, Chen K, Hawkins GA, Grant SC, Petty WJ, Alistar AT, Levine EA, Staren ED, Langefeld CD, Miller V, Singal G, Petro RM, Robinson M, Blackstock W, Powell BL, Wagner LI, Foley KL, Abraham E, Pasche B, Zhang W. Mutational Landscapes of Smoking-Related Cancers in Caucasians and African Americans: Precision Oncology Perspectives at Wake Forest Baptist Comprehensive Cancer Center, Theranostics. 2017; 7(11):2914-2923. doi:10.7150/thno.20355
Ryan, Bríd M. Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans, Clinical Cancer Research. (December 2017).