Hereditary Cancer Syndromes Flashcards
CHEK2
Considered a moderate-risk mutation, it may double or triple the carrier’s lifetime risk of breast cancer, and also increase the risk of colon cancer and prostate cancer.
Mutation associated with Cowden syndrome
PTEN
Gene’s most commonly implicated in hereditary cancer syndromes
BRCA1/2, cadherin 1 (CDH1), partner and localizer of BRCA2 (PALB2), phosphatase and tensin homolog (PTEN), and tumor protein p53 (TP53) [17]. We also include other genes such as ataxia-telangiectasia mutated (ATM), checkpoint kinase 2 (CHEK2),
Term for the extension of testing in families after the identification of a pathogenic variant is
cascade testing
Hereditary cancer syndrome associated with p53 mutation
Li Fraumeni syndrome
Cancers associated with lynch syndrome
CRC, uterine, renal, pancreatic
Management of patient with pMMR testing and high pre-test for lynch
Check for MSI status (MMR IHC testing has significant false negative rate of 5-10%)
Initial testing for Lynch syndrome
IHC testing for protein expression of 4 MMR genes or PCR
BRCA type associated with triple negative breast cancer
BRCA1
CDH1 is associated with
Hereditary diffuse gastric cancer
p53 mutation and breast cancer association
HER2-positive breast cancer
Cowden syndrome pathophys
upregulation of MTOR pathway
Cowden syndrome inheritance
Autosomal dominant
Cowden syndrome malignancies
endometrial, colon, breast, follicular thyroid
Cowden syndrome management
- mammography by age 30 or 5 years before earliest diagnosed BC in family
- annual thyroid US
- C-scope by age 35
- NO endometrial cancer screening
Other clinical features of FAP syndrome
- papillary thyroid cancer
- CHRPE (congenital hypertrophy of the retinal pigment epithelium – dark spot in eye)
- benign bone tumors, Desmond tumors, sebaceous cysts, supernumerary teeth
Mutation in Peutz-Jeghers syndrome
STK11
Peutz-Jeghers presentation
- hyper pigmented macules in mouth, nose, eyes, genitalia, and fingers
- harmatomatous polyps in GI tract
Cancers associated with Peutz-Jeghers
breast (most common), CRC, stomach, small bowel, pancreas
Peutz-Jeghers inheritance
Autosomal dominant
Peutz-Jeghers surveillance
- annual mammogram starting around age 25
- C-scope and EGD q2 years
- small bowel examination starting at age 8
- MRCP q1 year around 30
- pap smears, testicular exams
most common inheritance pattern of hereditary cancer syndrome
autosomal dominant
typical underlying genetic defect in hereditary cancer syndrome
typically it’s an inactivating mutation in a tumor suppressor gene rather than an activating mutation in an oncogene
penetrance of hereditary cancer syndromes
- there’s often incomplete penetrance
