Introduction

FAP is a disorder characterized by an autosomal dominant mutation of the APC gene. Duodenal adenomas are indeed found in 60–90% of patients with FAP. Gastric polyps in FAP patients are found in 30–100% of cases and most of them are fundic gland polyps. Some patients have a neoplastic phenotype (low grade/high grade dysplasia or adenocarcinoma). Shimamoto et al. tried to explain this condition: they subdivided the APC gene into six groups (from A to F), each one corresponding to a codon range, and evaluated the phenotypic correlation for each of these regions. They found an association between APC variants in codons 1398– 1580 (Region E) and neoplastic gastric and duodenal lesions.

Aims & Methods

The aim of our pilot study is to investigate the correlation between the different APC mutations and the presence of neoplastic gastric and duodenal phenotype in our case series of FAP patients.
We analysed 37 patients followed by our center for an average of 10 years: the APC gene was subdevided into six groups (from A to F) according to Shimamoto er al, each one corresponding to a codon range, and we studied the correlation between genotype and phenotypic manifestation of gastric and duodenal lesions according to their clinical history.

Results

We collected two patients with a mutation in region E: both developed gastric polyposis with low grade dysplasia (LGD) and high grade dysplasia (HGD) lesions of the duodenum. We also observed that two out of the three patients with mutation in region D (1250–1398) progressed to gastric cancer and duodenal cancer respectively. In Shimamoto’s study region B (454–1020) appears to be associated with a low risk of developing gastric lesions and a moderate risk of duodenal polyposis (Spigelman ≥ III), while our analysis shows that two (out of 12) of the patients mutated in this region developed gastric cancer and two developed duodenal cancer. In our case series two patients had the mutation at the promoter level of the APC gene, and this correlates with GAPPS (Gastric Adenocarcinoma and Proximal Polyposis of the Stomach): a newly discovered disease that has a very high risk of gastric adenocarcinoma typically without duodenal polyps.

Conclusion

Currently there are no precise guidelines for upper gastro-intestinal tract endoscopy based on genetic mutations. This pilot study highlights the need for further research to establish an evidence based consensus.

References

Shimamoto Y, Takeuchi Y, Ishiguro S, Nakatsuka SI, Yunokizaki H, Ezoe Y, Nakajima T, Tanaka K, Ishihara R, Takayama T, Yoshida T, Sugano K, Mutoh M, Ishikawa H. Genotype-phenotype correlation for extracolonic aggressive phenotypes in patients with familial adenomatous polyposis. Cancer Sci. 2023 Dec;114(12):4596-4606.