Cancer is a disease that is influenced by both extrinsic and genetic factors. These factors can be protective or deleterious. Gene-extrinsic factor interactions could provide valuable insights into chemicals that are potentially protective or toxic.
Suxia Han of Xi’an Jiaotong University, China, and colleagues investigated the correlation between chemicals and colorectal cancer using integrated data from the Comparative Toxicogenomics Database (CTD), genome-wide association (GWAS) summary datasets from the UK biobank Gene ATLAS, and gene expression profiles from the GEO database. The results were published in the journal frontiers in Genetics.
From the GWAS summary dataset of colorectal cancer patients the researchers identified 271 chemicals associated (positive or negative) with colon or rectal cancer. From the GEO gene expression dataset 1,198 chemicals were significantly associated with colorectal cancer. The GWAS and gene expression datasets shared 150 chemical associations for colorectal cancer. Methylnitronitrosoguanidine, isoniazid, PD 0325901, sulindac sulfide, and importazole were associated with both colon and rectal cancer.
Methylnitronitrosoguanidine is a known probable human carcinogen listed as an IARC Group 2A carcinogen. Isoniazid is an antibiotic often used to treat latent and active tuberculosis infections. PD0325901 is an investigative selective and non ATP-competitive MEK inhibitor. Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the arylalkanoic acid class. Some preclinical studies suggest anti-cancer effects. Importazole is a small molecule inhibitor of the nuclear transport receptor importin-β.
The study is limited by the fact that it is making indirect associations between independent datasets of genome loci, mRNA expression and chemicals in the CRD database. The associations may not be causal and any novel associations would require follow-up.
“In summary, we conducted an integrative analysis of GWAS summary data, mRNA expression profiles and chemical-gene interaction networks. Tools such as TWAS and GSEA helped linking these datasets and identifying several chemicals associated with CRC. The results of our study evaluate the associations between CRC and chemicals systematically, and provide new clues for revealing the association between chemicals and genes and their effects on cancer. Furthermore, our method can be used to analyze other chemicals and complex malignant disease, which is helpful for assessing the relationship between environmental exposure and cancer,” stated the authors.