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

Patients with a pathogenic variant in the ATM gene have an increased risk of cancer, which may include the rare condition ataxia telangiectasia.

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.

Birt-Hogg-Dubé syndrome is a rare autosomal dominant tumour predisposition condition characterised by cutaneous manifestations, pulmonary cysts predisposing to spontaneous pneumothorax, and an increased lifetime risk of renal cell carcinoma. It is caused by constitutional (germline) pathogenic variants in the FLCN gene.

MUTYH-associated polyposis (MAP) is an autosomal recessive cancer predisposition syndrome caused by biallelic pathogenic constitutional (germline) variants in the MUTYH gene.

APC-related familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome caused by pathogenic constitutional (germline) variants in the APC 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.

The identification of a heterozygous constitutional (germline) variant in a mismatch repair gene in a patient with colorectal cancer has implications for the clinical management of the current cancer and the patient’s future cancer risk. It should also trigger cascade screening in the wider family.

The identification of a somatic (tumour) pathogenic KRAS variant in a patient with colorectal cancer has implications for their clinical management.