| Autor: |
Cheng Wang, Juncheng Dai, Na Qin, Jingyi Fan, Hongxia Ma, Congcong Chen, Mingxing An, Jing Zhang, Caiwang Yan, Yayun Gu, Yuan Xie, Yuanlin He, Yue Jiang, Meng Zhu, Ci Song, Tao Jiang, Jia Liu, Jun Zhou, Nanxi Wang, Tingting Hua, Shuang Liang, Lu Wang, Jing Xu, Rong Yin, Liang Chen, Lin Xu, Guangfu Jin, Dongxin Lin, Zhibin Hu, Hongbing Shen |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cancer Cell. 40:1223-1239.e6 |
| ISSN: |
1535-6108 |
| DOI: |
10.1016/j.ccell.2022.08.013 |
| Popis: |
We present the largest whole-genome sequencing (WGS) study of non-small cell lung cancer (NSCLC) to date among 6,004 individuals of Chinese ancestry, coupled with 23,049 individuals genotyped by SNP array. We construct a high-quality haplotype reference panel for imputation and identify 20 common and low-frequency loci (minor allele frequency [MAF] ≥ 0.5%), including five loci that have never been reported before. For rare loss-of-function (LoF) variants (MAF 0.5%), we identify BRCA2 and 18 other cancer predisposition genes that affect 5.29% of individuals with NSCLC, and 98.91% (181 of 183) of LoF variants have not been linked previously to NSCLC risk. Promoter variants of BRCA2 also have a substantial effect on NSCLC risk, and their prevalence is comparable with BRCA2 LoF variants. The associations are validated in an independent case-control study including 4,410 individuals and a prospective cohort study including 23,826 individuals. Our findings not only provide a high-quality reference panel for future array-based association studies but depict the whole picture of rare pathogenic variants for NSCLC. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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