Colorectal cancer is the second most prevalent cancer worldwide, while gastric cancer shows an increasing frequency, especially in young people, accounting for over one million new patients in 2022. This study investigates the genetic associations between colorectal and gastric cancer.

We conducted a systematic review focusing on the genetic pathways associated with colorectal and gastric cancer. Articles were retrieved from the PubMed database. The inclusion criteria encompassed the keywords “genetics”, “colorectal cancer” and “gastric cancer” in papers published between 2023 and 2024. The exclusion criteria were case report papers.

A total of 56 articles met the eligibility criteria. Of these, eight articles explored Li–Fraumeni and Lynch syndromes, which are linked to a high risk of developing colorectal and gastric tumors due to mutations in the TP53 and MMR genes, respectively. Furthermore, 11 studies emphasized the elevated risk of malignancy due to gastrointestinal polyps in familial adenomatous polyposis (APC mutations); juvenile polyposis syndrome (SMAD4/BMPR1A mutations); and Peutz–Jeghers syndrome (STK11 mutations). We identified five studies that linked inflammatory bowel disease to colitis-associated colorectal carcinoma, driven by p53 mutations. Furthermore, three papers explored gastrointestinal stromal tumors, rare neoplasms that occur due to PDGFRA D842V mutations. Additionally, 29 articles showed that genetic mutations in the Wnt Signalling Pathway and KRAS gene, polymorphisms in nucleic acids and chemokine ligands promote carcinogenesis, tumor progression and invasion, indicating a higher risk of developing metastasis. One of the most relevant targets for developing new therapies is the Wnt receptor ROR1, which is overexpressed in several cancers and promotes Wnt Signalling Pathway hyperactivation, facilitating carcinogenesis.

Our findings suggest that genetic exploration serves as a predictive factor for the co-occurrence of colorectal and gastric cancer. Mutations in genes linked to genetic syndromes and signalling pathways are associated with an increased risk of gastrointestinal tumorigenesis, particularly involving the interplay between colorectal and gastric tumors.