Genetic correlation, and causal relationships between 3 solid cancer types and human traits

Solid cancers are the most prevalent malignancies with rising trend and mortality worldwide. Behavioural risk factors for these cancers are not completely clear, and the effect of genetic factors for their development remains unknown. This study investigates the genetic relationship between 3 solid cancer types with other human traits. We used linkage disequilibrium score regression (LDSC) to analyze the links between lung carcinoma, esophageal carcinoma and colon cancer, and several phenotypes that include smoking, habits and body measurements. We then applied a latent causal variable (LCV) approach to elucidate their causal effects. Finally, we performed a gene selection for each cancer type using genome wide association studies and gene expression profiles. LDSC revealed a significant association of the 3 cancer types with body mass index, while causative effect analysis identified that the trait “Exposure to tobacco smoke at home” showed a causal effect on lung squamous cancer. Further analysis identified shared gene loci using gene expression profiles and GWAS including BRCA2, HLA-DQB1, SLC44A4, and ZNF623 in lung squamous cell carcinoma, COCH, CHRM3, SYNPO2, and TAF4B in esophageal adenocarcinoma, and BMP4, and SYN3 in colorectal cancer. This study suggests novel insights into the genetic links between lung carcinoma, esophageal carcinoma and colon cancer. Utilising computational approaches for genetic correlation, causal assessment, and gene selection, we identified shared genetic susceptibilities and specific genetic mechanisms. These findings revealed new targets to further elucidate the genetic basis of these 3 solid cancers, and for the development of preventive and therapeutic approaches.