Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Nat Commun. 2023 Jun 20;14(1):3671. doi: 10.1038/s41467-023-39136-7.
Integrating genomic data of multiple cancers allows de novo cancer grouping and elucidating the shared genetic basis across cancers. Here, we conduct the pan-cancer and cross-population genome-wide association study (GWAS) meta-analysis and replication studies on 13 cancers including 250,015 East Asians (Biobank Japan) and 377,441 Europeans (UK Biobank). We identify ten cancer risk variants including five pleiotropic associations (e.g., rs2076295 at DSP on 6p24 associated with lung cancer and rs2525548 at TRIM4 on 7q22 nominally associated with six cancers). Quantifying shared heritability among the cancers detects positive genetic correlations between breast and prostate cancer across populations. Common genetic components increase the statistical power, and the large-scale meta-analysis of 277,896 breast/prostate cancer cases and 901,858 controls identifies 91 newly genome-wide significant loci. Enrichment analysis of pathways and cell types reveals shared genetic backgrounds across said cancers. Focusing on genetically correlated cancers can contribute to enhancing our insights into carcinogenesis.
整合多种癌症的基因组数据可以对癌症进行重新分组，并阐明癌症之间的共同遗传基础。在这里，我们对包括 250015 名东亚人（日本生物银行）和 377441 名欧洲人（英国生物银行）在内的 13 种癌症进行了泛癌症和跨人群全基因组关联研究（GWAS）荟萃分析和复制研究。我们确定了 10 个癌症风险变异，包括 5 个多效关联（例如，位于 6p24 的 DSP 上的 rs2076295 与肺癌相关，位于 7q22 的 TRIM4 上的 rs2525548 与六种癌症名义相关）。量化癌症之间的共享遗传率可以检测到人群中乳腺癌和前列腺癌之间的正遗传相关性。共同的遗传成分增加了统计能力，对 277896 例乳腺癌/前列腺癌病例和 901858 例对照的大规模荟萃分析确定了 91 个新的全基因组显著位点。对途径和细胞类型的富集分析揭示了这些癌症之间的共同遗传背景。关注遗传相关的癌症可以帮助我们深入了解致癌作用。
