Hereditary cancer syndromes (HCS) account for 5–10% of all cancer. Most patients at risk of HCS will report a family history of cancer and some may know the cause of the family history due to the identification of a pathogenic gene mutation. For young patients with a diagnosis of cancer, genetic investigations can inform cancer treatment, fertility preservation and cancer prevention through surveillance and/or risk-reducing measures. However, patients with HCS also have specific issues related to their reproductive options.1,2
HEREDITARY CANCER SYNDROMES
Patients with young-onset cancer consistent with HCS may report a family history of associated cancer(s). The patient or their family member(s) may also have bilateral tumours, multiple primary cancers in an individual or have a specific histological cancer sub-type for which genetic investigations are warranted. Figure 11.1 represents a hereditary breast and ovarian cancer syndrome history, with the proband harbouring a BRCA1 mutation after developing a ‘triple-negative receptor’ breast cancer. Once a pathogenic mutation has been identified in a patient, their at-risk relatives can access predictive genetic testing to determine their personal risks and options of additional screening or risk-reducing surgery.
Family tree of hereditary breast and ovarian cancer syndrome caused by a BRCA1 mutation. The majority of the common HCS are inherited in an autosomal dominant manner, leading to a 1 in 2 chance (50% risk) of the pathogenic gene mutation being passed to offspring, with only a few syndromes being transmitted in an autosomal recessive inheritance pattern as outlined in Table 11.1.
Table 11.1Common hereditary cancer syndromes |Favorite Table|Download (.pdf) Table 11.1 Common hereditary cancer syndromes
|Malignancy ||Gene ||Syndrome ||Population frequency ||Inheritance pattern |
|Breast ||BRCA1 and BRCA2 ||Hereditary breast and ovarian cancer ||1/400–1/800 ||AD1 |
| ||PALB2 ||Hereditary breast cancer ||1/181 ||AD |
| ||TP53 ||Li-Fraumeni syndrome ||1/5000–1/20,000 ||AD |
| ||STK11 ||Peutz-Jeghers syndrome ||1/155,000 ||AD |
| ||PTEN ||Cowden syndrome ||1/200,000 ||AD |
| ||CDH1 ||Hereditary diffuse gastric cancer ||Unknown ||AD |
|Colorectal ||MLH1, MSH2, MSH6, PMS2, EPCAM ||Lynch syndrome (hereditary nonpolyposis colorectal cancer) ||1/440 ||AD |
| ||APC ||Familial adenomatous polyposis ||1/16,850–1/31,250 ||AD |
| ||MUTYH ||MYH-associated polyposis ||1/20,000–1/60,000 ||AR2 |
|Endocrine ||MEN1 ||Multiple Endocrine Neoplasia Type1 ||1/10,000–1/100,000 ||AD |
| ||RET ||Multiple Endocrine Neoplasia Type 2 ||1/35,000 ||AD |
| ||SDHA, SDHB, SDHC, SDHD, SDHAF2, MAX, TMEM127 ||Hereditary Pheochromocytoma/Paraganglioma Syndrome ||Unknown ||AD |
| ||VHL ||Von-Hippel-Lindau Syndrome ||1/36,000 ||AD |
|Intraocular ||RB1 ||Familial Retinoblastoma ||1/15,000–1/20,000 ||AD |
|Neurological ||NF1 ||Neurofibromatosis type 1 ||1/3000 ||AD |
Despite technological advances, genetic test results are also not always straightforward. A broad approach to genetic testing can reveal unclear or incidental findings that may lead to uncertainty for patients. Genetic investigations ...