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 study 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 genome-wide association studies (GWAS) loci and explained an average of 2% for 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. Significance: This study provides insights into the host–microbiome interactions for multiple cancer types, which could help the research community understand the effects of inherited variants in tumorigenesis and development.

中文翻译：

---

微生物组数量性状基因座的泛癌症分析

微生物通常在肿瘤组织中检测到，据报道微生物的种类和丰度会影响癌症的发生、进展和治疗。宿主遗传学与肠道微生物丰度相关，而遗传变异与癌症微生物组之间的关系仍需要系统研究。因此，跨癌症类型的癌症微生物组数量性状位点（mbQTL）的鉴定可能会阐明遗传变异对肿瘤发展的贡献。利用癌症基因组图谱中的基因型数据和 Kraken 衍生数据中的微生物丰度水平，我们开发了一个计算流程来识别 32 种癌症类型中的 mbQTL。这项研究系统地鉴定了多种癌症的 38,660 个 mbQTL，其中子宫内膜癌有 50 个，甲状腺癌有 3,133 个。此外，在转录因子结合位点和染色质调控元件（例如 H3K27ac）中观察到 mbQTL 的强烈富集。值得注意的是，mbQTL 在癌症全基因组关联研究 (GWAS) 位点中显着富集，并平均解释了 2% 的癌症遗传力，表明 mbQTL 可以为癌症病因学提供更多见解。相应地，鉴定了 24,443 个与 GWAS 连锁不平衡区域重叠的 mbQTL。生存分析确定了 318 个与患者总体生存相关的 mbQTL。此外，我们发现了 135,248 个微生物组-免疫浸润关联和 166,603 个微生物组-药物反应关联，这可能为基于微生物组的生物标志物提供线索。最后构建了一个用户友好的数据库Cancer-mbQTL（http://canmbqtl.whu.edu.cn/#/）供用户浏览，搜索并下载感兴趣的数据。这项研究为研究遗传学和微生物在人类癌症中的作用提供了宝贵的资源。意义：这项研究提供了对多种癌症类型的宿主-微生物组相互作用的见解，这可以帮助研究界了解遗传变异对肿瘤发生和发展的影响。