Pan-cancer analysis of microbiome quantitative trait loci
Pan-cancer analysis of microbiome quantitative trait loci
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DOI：
10.1158/0008-5472.can-22-1854
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Fu
中科院分区：
文献类型：
--
作者：
Chen Can;Cai Yimin;Liu Yizhuo;Chen Shuoni;Li Yanmin;Zhang Fuwei;Zhang Ming;Lu Zequn;Ying Pingting;Huang Jinyu;Fan Linyun;Cai Xiaomin;Ning Caibo;Wang Wenzhuo;Jiang Yuan;Zhang Heng;Yang Shuhui;Wang Zhihua;Wang Xiaoyang;Zhang Shaokai;Huang Chao-qun;Xu Bin;Fu
Abstract Microorganisms are commonly detected in tumor tissues, and the species and abundance have been reported to affect cancer initiation, progression, and therapy. Host genetics have been associated with gut microbial abundances, while the relationships between genetic variants and the cancer microbiome still require systematic interrogation. Therefore, identification of cancer microbiome quantitative trait loci (mbQTL) across cancer types might elucidate the contributions of genetic variants to tumor development. Using genotype data from The Cancer Genome Atlas and microbial abundance levels from Kraken-derived data, we developed a computational pipeline to identify mbQTLs in 32 cancer types. This systematically identified 38,660 mbQTLs across cancers, ranging 50 in endometrial carcinoma to 3,133 in thyroid carcinoma. Furthermore, a strong enrichment of mbQTLs was observed among transcription factor binding sites and chromatin regulatory elements, such as H3K27ac. Notably, mbQTLs were significantly enriched in cancer GWAS loci and explained an average of 2% of cancer heritability, indicating that mbQTLs could provide additional insights into cancer etiology. Correspondingly, 24,443 mbQTLs overlapping with GWAS linkage disequilibrium regions were identified. Survival analyses identified 318 mbQTLs associated with patient overall survival. Moreover, we uncovered 135,248 microbiome-immune infiltration associations and 166,603 microbiome-drug response associations that might provide clues for microbiome-based biomarkers. Finally, a user-friendly database, Cancer-mbQTL (http://canmbqtl.whu.edu.cn//), was constructed for users to browse, search, and download data of interest. This study provides a valuable resource for investigating the roles of genetics and microorganisms in human cancer.
