Genetic risk factors for nasopharyngeal carcinoma have been identified through China-based research conducted by the Sun Yat-sen University Cancer Center. The international team used multiple genomic approaches to identify genes that are crucial to the development of nasopharyngeal carcinoma in a paper that was published in The American Journal of Human Genetics and titled “High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma.”
Nasopharyngeal carcinoma (NPC) is a deadly cancer that starts in the upper part of the throat behind the nose and is linked to Epstein-Barr virus infection. Mononucleosis, or “mono,” is a herpes virus. Because of their widespread prevalence, Epstein-Barr infections infect the majority of humans at some point.
The Epstein-Barr virus has been linked to NPC, and people of Chinese descent are more likely to get it. The fact that 77% of new cases of NPC worldwide occur in east and southeast Asia indicates a significant genetic risk factor for the disease’s development.
Numerous genetic links between NPC and previous work by the team and other research institutions have been found. The net cast by these past examinations was wide, leaving explicit illness instruments concealed inside the bigger trap of collaborations.
In order to identify additional NPC susceptibility loci, the current study performed genetic associations by combining 6,907 cases and 10,472 controls. The significance of the DNA damage repair pathway and the possibility that the genes PHF2 and CDKN2B-AS1 are crucial to the development of NPC are highlighted by the findings.
To better support the connection between NPC susceptibility and single nucleotide polymorphisms (SNPs), the study combined epidemiological research with genomic profiling and experiments. When SNPs have risk or protective alleles, they discovered that cis-regulatory sequences have different regulatory activities.
By controlling access to genes, cis-regulatory sequences like enhancers and promoters can control physiology by influencing when and how intensely genes are expressed.
The identified risk alleles inhibited the expression of the target gene PHF2 by reducing the enhancer activity of a regulatory element. Decrease of PHF2 advanced cell expansion and clonogenicity, recommending its job as a cancer silencer in NPC.
CDKN2B-AS1 expression increased as a result of the risk alleles in the same locus increasing the enhancer activity of another regulatory element. Overexpression of CDKN2B-AS1 advanced cell expansion and clonogenicity, showing its oncogenic role in NPC.
The researchers say that the found SNPs could be used as biomarkers to predict NPC risk and that more research is needed to figure out how the susceptibility genes work on the molecular level.
More information: Tong-Min Wang et al, High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma, The American Journal of Human Genetics (2023). DOI: 10.1016/j.ajhg.2023.06.003
