OnSeptember 15, 2022, Dr. Hongbing Shen, Dr. Zhibin Hu and theircolleagues from SHEN Hongbing and HU Zhibin research group of ourschool university published in the leading international journalCancercellone a research article entitled "system SAnalyses of rarepredisposing variants of lung cancer in 6004 whole genomes inChineseystem based on whole genome sequencing technology analyzedChina crowd lung Cancer cancer rare germ pathogenic mutation"(Analyses of rare predisposing variants of lung cancer in 6004 wholegenomes in Chinesein Cancercell.

Lungcancer is the leading type of malignancies with the highest incidenceand mortalitymost common malignant tumor in China. In the past twodecades, imputation-based large-sample Ggenome-wide associationstudies (GWASs) based on high-throughput microarray and genotypeimputing strategy have been widely used in the susceptibility studyof lung cancer and have identified effectively identified more than80 genetic genetic variants that contributed related to thesusceptibility of pathogenesis in non-small cell lung cancer (NSCLC)cases. But However, traditional array-based GWASs there are stillhave some limitations: On the one handFirst of all, traditional GWASsbased on  imputation of genotypes from SNP array with a pre-builthaplotype referencemicroarray detection of whole genome genotypes isbased on imputation technology. Thus, , and its the imputationefficiency largely accuracy depends largely on athe high-quality andancestry compatibility of ancestry-matchedthe  referencepopulationmatching and more comprehensive and accurate haplotype referencedatabase. However, tThe current existingwidely-used panels arepredominantly composed of individuals of European descentthe existingreference database mainly consists of European and Americanpopulations, which greatly limiting the imputation quality and studypower forof the GWASs in the Chinese populationand the large-scaleand high-quality reference database of Chinese population needs to befurther enriched. On the other handSecond, even though thearray-based imputation strategy enabled us to investigate more than90% of the common and low-frequency variants, it can hardly beapplied to the rare variants, which make up the vast majority ofhuman variants the chip imputation strategy is only suitable for thestudy of common and low-frequency variants, and the ability toanalyze rare pathogenic variants is insufficient.

Dr.Hongbing Shen, Dr. Zhibin Hu and their colleaguesDr. Hongbing Shen,Dr. Zhibin Hu and their colleaguesSHEN Hongbing and HU Zhibinresearch group applied a large-scale wWhole-genome sequencing (WGS)of 2,984 NSCLC cases and 3,020 non-cancer controls, technology toandperformed WGS-based genome-wide association studiesGWAS of NSCLC forthe first time. They not only constructed a high-qualityChinese-specific haplotype reference library of haplotypespanelspecific to the Chinese population, but also discovered identifiedseveral novel common and low-frequency susceptibility variantsassociated withfor NSCLC. At the same timeIn addition, theysystematically evaluated the pathogenicity of rare variants in codingsequence and regulatory regionsthe rare pathogenic variants in thecoding and regulatory regions of NSCLC were systematically analyzed.They identified that rare pathogenic variants in the promoter regionof BRCA2could increase the risk of NSCLC by 8.84 timesFor the first time,they found that the rare pathogenic variants in the BRCA2 promoterregion increased the risk of lung cancer by 8.84 times, and theeffect was not differentsimilar among between men and women. Thepredictive power performance of BRCA2promoter variants on the risk of lung cancer was further evaluated inan independent  prospective cohort study.

Insummary, this research In this study, whole-genome sequencing wassuccessfully applied WGS to the research study of lung cancergenomicsgenetics, and systematically evaluated and thecommon/low-frequency susceptibility variants and rare pathogenicvariants of lung cancer were systematically discovered, whichprovided a new idea strategy for fully revealing investigating thegenetic pattern of lung cancer, and also provided a large number ofcandidate variants for genetic detection of lung cancer. Thesefindings can help optimize the risk stratification for lung cancer,which adds important evidence to the further surveillance practicesand clinical care recommendations for lung cancerare helpful toimprove the identification strategy of high-risk groups of lungcancer and provide a new theoretical basis for precise prevention oflung cancer. . In addition, the identified lung cancer-associatedpathogenic genetic variants may also serve as candidates for genetictesting in clinics In addition, the discovery of rare and potentpathogenic variants in lung cancer provides candidate sites forfuture genetic detection andas well as the intervention targets inthe early embryonic stage, and which will further improves theprevention and control of major diseases. The query “OMICS”platform constructed in this study also provides a high-quality keybasic reference data for medical and genetic researches in China andeven East Asia.

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