Wei-Hua Jia (Sun Yat-sen University Cancer Center, China)
“Genetic Predisposition of Nasopharyngeal Carcinoma: Evidence from GWAS and Sequencing Studies”
# Spatial and temporal patterns of MNOC mortality in China (1973-2005) showed significant decreased
Compared with those living in North China, residents living in Southern China had a much higher risk in the
Familial clustering has been observed not only in high-risk areas of
A genome-wide complex trait analysis to estimate heritability explained by common SNPs in GWAS array. (In T Cancer 2017).
GWS predicts 9 common SNPs
Heritability estimation acplaind by common SNPs
Novel genetic variant s of NOC need to be discovered. *Common and moderate loci, especially for those casual or functional
Whole exonerated sequecning study of familial NOC (to identify
Screening program for NPC multiple families (endoscopic examination of the nasopharyngeal, detection of EBV antibody, detection of
By June 2018, we have collected a total of 144 NOC multiplex families.,,, (60% of them has at least 3 NPC patients in the families)
Whole exonerated-seq
Total: 57,000 novel variant totally, most of which are rare
(Compared to DsSNP, 1000 Genomic…databsese
Women-side association analysis of confirmed SNP (e.g HLA I, chromosome 19…
Most of the identified variants in HLA are located in the HLA region
Novel functional variants may influence the role of HLA on antigen recognition, process and presentation
—HLA-DAB1 3 UTR
Rare and deleterious variants were bricked in NPC familial cases with high odds ration
Rare (MA < 0.01, 1000 genome, ). And deleterious (splicing, frameshift indels, stop gain./loss, nonsense
POLN gene was cosegregation with affected members of a. SIHUI family
-PLON is a member of FNA polymerase family, plays a role in FNAS repair and homologous recombination
POLN P577L mutation reduced the function of DNA damage repair of POLM (by Host cell reactivation assay)
Lower POLN expression was shown in both NPC tumor tissues and NPC cell lines
Rare SNPs rate is very low (often < 1%) in NPC compared to other cancers (eg BrCA), implicating that the genetics are very heterogeneous.
Some of the variants are quite related to EBV infection
Receptor for EBV infection
Immune initiating immune
highly expressed in saliva