Juvenile polyposis syndrome is a rare autosomal dominant precancerous condition associated with an increased risk of gastrointestinal (GI) tract cancers.

Genomic testing in carcinoma of unknown primary may have implications for the clinical management of the patient’s current cancer, as well for their family members.

Advice for patients with cancer whose constitutional (germline) genomic testing results are uninformative should be guided not just by their negative result, but also by their personal and family history. The patient and their relatives may still require enhanced cancer screening.

Peutz-Jeghers syndrome is characterised by hamartomatous bowel polyps and mucocutaneous pigmentation, and is associated with an increased risk of a variety of cancers. It is caused by constitutional (germline) pathogenic variants in the serine/threonine kinase 11 (STK11) gene.

Individuals with certain constitutional (germline) variants in the dihydropyrimidine dehydrogenase (DPYD) gene are prone to developing severe adverse reactions to fluoropyrimidine-based chemotherapies, for example, 5-fluorouracil, capecitabine, tegafur.

Constitutional (germline) genomic testing of patients with lobular breast cancer and a strong family of diffuse gastric cancer for pathogenic variants of CDH1/CTNNA1 can result in a diagnosis of hereditary diffuse gastric cancer.

Genomic testing of individuals presenting at a young age with diffuse-type gastric cancer can allow identification of at-risk family members and inform the need for screening of other associated malignancies.

Gastric cancer is the 17th most common cancer in the UK and is responsible for more than 4,000 deaths annually. Up to 3% of all gastric cancers are a result of hereditary syndromes.

Hereditary diffuse gastric cancer syndrome is an autosomal dominant cancer syndrome principally caused by inactivating variants in the CDH1 gene.