Genetically predicted causal associations between 152 blood-related exposures and pan-cancer in the framework of prediction, prevention and personalized medicine: a study integrating Mendelian randomization and bioinformatics
Authors: tang Xinhao , tian Xinyu , Wu Jingjing , Hao Sainan , Chu Bowen , Shi Jun , Li Zimo , Shan Shuai , Dai Tinghao , Tang Guanmin , Xu Wenbo , Wu Mianhua 
Published: January 2024

Objective
Blood serves as a powerful tool for monitoring the intricate landscape of cancer development. Previous studies have emerged, suggesting that hematologic indicators hold promise in predicting the onset of malignancy. This present investigation aims to delve into the underlying causal connections between blood-related indicators and pan-cancer, further elucidating the potential impact of diseases and medication utilization reflected in these indicators on cancer, within the realm of predictive, preventive and personalised medicine(PPPM).
Methods
To embark on this scientific endeavor, we procured summary-level data from a genome-wide association studies (GWAS) encompassing blood-related indicators and cis-eQTLs of drug target genes, from the esteemed IEU OpenGWAS. Additionally, we obtained GWAS summary-level data encapsulating pan-cancer (consisting of an impressive cohort of 659,582 cases and 12,186,911 controls), along with diseases annotated by their correlation to blood-related indicators, from esteemed sources such as IEU OpenGWAS, UK Biobank, FinnGen, and Biobank Japan. In order to unravel the direct causal associations between blood-related indicators and pan-cancer, as well as the causal implications between the diseases manifested by these indicators and cancer, we initiated a robust analysis employing the two-sample Mendelian randomization(MR) method. Furthermore, utilizing bioinformatics methodologies, we went on to explore the potential effects of drug target genes on pan-cancer.
Results
Preliminary findings from our MR analysis provided compelling evidence of a significant link between blood-related exposures and pan-cancer. Drawing upon the intriguing interplay observed between blood pressure and tumors, it was postulated that monitoring hypertension (HTN) may offer notable advantages in the prevention of colorectal adenocarcinoma (COAD), breast carcinoma (BRCA), and esophageal carcinoma (ESCA). Similarly, considering the captivating relationship between blood glucose, insulin levels, and tumors, it was hypothesized that closely monitoring diabetes mellitus (DM) could prove beneficial in the prevention of stomach adenocarcinoma (STAD) and COAD. In consonance with the intriguing connection discovered between red blood cell counts, distribution width, and tumors, our findings supported the notion that monitoring anemia could impart advantageous effects in the prevention of lung adenocarcinoma (LUAD). Remarkably, drawing upon the intriguing relationship observed between deep vein thrombosis (DVT) and tumors, it was hypothesized that surveillance of DVT might prove valuable in the prevention of COAD. Additionally, we noted a disparity in risk for various cancers, including lung, breast, colorectal, ovarian, prostate, and pancreatic, consequent to the utilization of drugs for these aforementioned diseases. Among our identified drug targets, we carefully sifted through and diligently analyzed three pivotal genes, namely HMGCR, INSR, and NR3C1, fostering the prospect of formulating novel, tumor-targeted therapeutics. However, our investigation yielded insufficient evidence to confirm any mediating effects of glycated hemoglobin (HbA1c), hemoglobin-gastric, D-dimer, and renin on the associations between HTN, anemia, DVT, DM, and pan-cancer.
Conclusions
The present study unveils the intricate web of causal associations between blood-related indicators, the diseases they manifest, and medication utilization, all of which significantly impact the development of cancer. Notably, the potential for utilizing blood-related indicators as pioneering biomarkers for cancer prediction and prevention is underscored, showcasing a remarkable avenue for advancing PPPM strategies in the field of oncology. This seminal investigation serves as a beacon of novel insight, engendering the construction of refined and tailored approaches to combat the formidable challenge of cancer.