Recurrently Mutated Genes in Liver Hepatocelluar Carcinoma and Racial Disparity: An Analysis of TCGA Data
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Liver hepatocellular carcinoma (LIHC) is one of the most common types of cancer, with the third highest incidence rate of any cancer worldwide. However, the distribution of this cancer varies between populations, with the incidence rate of LIHC in Asian-Pacific Islanders over twice that of Caucasians in the US. This has been attributed in part to differential exposure rates of several LIHC risk factors, including higher Hepatitis B and aflatoxin. However, to our knowledge, there is a lack of knowledge on the genetic mechanisms underlying liver carcinogenesis between the two different ethnic groups. We thus initiated this study to compare the mutational landscapes of LIHC between Asian and Caucasian populations. We have analyzed publically available whole-exome sequencing data from The Cancer Genome Atlas (TCGA) for 53 Asian and 103 Caucasian LIHC patients, preforming single nucleotide variant (SNV), copy number variant (CNV), and risk factor comparison between the two populations. We found six genes mutated at a significantly higher rate in Asians compared with Caucasians, of which only two significantly correlated with known risk factors. At a CNV level, we found potential differences in deletion of immune regulatory cytokines, including anti-inflammatory cytokines in Caucasians, as well as differential regulation of growth factors. The differences in mutational landscapes between Asians and Caucasians may have implications for the ethnicity associated differences in LIHC incidence and outcome. Additional confirmation is needed due to the limited sample size of this study.