Hereditary Cancer Syndromes Flashcards
(54 cards)
1
Q
HBOC-related cancers
A
- Breast (higher in BRCA1)
- Ovarian (higher in BRCA1)
- Pancreatic (higher in BRCA2)
- Prostate (BRCA2)
- Melanoma (BRCA2)
2
Q
HBOC Risk Models
A
- Gail - breast cancer risk only - excludes paternal family hx
- Claus - breast cancer risk only - unaffected probands only
- Couch/Penn II - BRCA mutation risk only
- Myriad tables - BRCA mutation risk only
- BRCApro - breast cancer and BRCA mutation risk
- Tyrer-Cuzick (IBIS) - Breast cancer and BRCA mutation risk
3
Q
HBOC-related genes
A
- Primary
- BRCA1, BRCA2
- Breast cancer risk genes
- PTEN, TP53, CHEK2, CDH1, ATM, BRIP1, PALB2, NBN
- Ovarian cancer risk genes
- MLH1, MSH2, MSH6, PMS2
4
Q
PTEN-associated cancers
A
- Breast
- Thyroid - follicular
- Colon
- Uterine
- Kidney
5
Q
Other features of PTEN
A
- Hamartomatous polyps
- Skin lesions - trichilemmomas, lipomas, acral keratoses
- Overgrowth - macrocephaly
6
Q
Cowden Syndrome
A
- PTEN-associated syndrome
- Autism
- Macrocephaly
- Skin lesions - acral keratoses, lipomas, trichilemmomas
- Hamartomatous GI polyps
- Thyroid nodules
- PTEN-associated cancer risks
7
Q
Bannayan-Riley-Ruvalcaba Syndrome
A
- Childhood onset
- Autism
- Developmental delay
- Macrocephaly
- Penile skin macules
- Goiter
- Hyperextensibility
8
Q
Lhermitte-Duclos Disease
A
- PTEN-associated
- Dysplastic gangliocytoma of the cerebellum (benign)
9
Q
CDH1 - Associated Cancers
A
- Diffuse gastric
- Lobular breast
- Colon
- Prostate
10
Q
CDH1-mutation management
A
Prophylactic gastrectomy is recommended for mutation-positive individuals with a family hx of gastric cancer
11
Q
Li-Fraumeni - Associated cancers
A
- Breast
- Brain
- Leukemia
- Adrenocortical carcinoma
- Sarcoma
- Choroid plexus tumors
12
Q
Chompret Criteria
A
- Proband with LFS-associated cancer before age 46
- And at least one first or second-degree relative with an LFS-associated tumor before age 56/multiple tumors
OR
- Proband with multiple tumors, two of which are LFS-related, the first of which occurred before age 46
- Excludes multiple breast tumors
OR
- Patient with adrenocortical carcinoma or choroid plexus tumor regardless of family hx
13
Q
HNPCC-related cancers
A
- Colon
- Ovarian
- Uterine
- Stomach
- Gallbladder
- Urinary bladder
- Brain
- Small bowel
14
Q
Amsterdam Criteria
A
- At least 3 individuals with HNPCC-related tumors
- 1 should be a first degree relative of the others
- At least 2 successive generations affected
- At least 1 relative diagnosed before age 50
15
Q
Bethesda Criteria
A
- CRC diagnosed under age 50
- Presence of synchronous or metachronous HNPCC-related tumors regardless of age of diagnosis
- MSI-H histology CRC tumor under age 60
- CRC diagnosed in one or more first degree relatives with an HNPCC-associated tumor
- At least one of the tumors diagnosed before age 50
- CRC diagnosed in two or more first or second-degree relatives regardless of age of diagnosis
This criteria is more sensitive than Amsterdam
16
Q
HNPCC/Lynch genes
A
[MLH1, PMS2]
[MSH2, MSH6]
EPCAM
17
Q
Familial Adenomatous Polyposis
A
100+ adenomas in the colorectum
Can onset as early as childhood
18
Q
FAP-Associated cancers
A
- Pancreatic
- Adrenal gland
- Thyroid
- Colon
- Hepatobiliary
- Duodenum
19
Q
Gardner Syndrome
A
- FAP with additional findings
- Osteomas
- Additional desmoid tumors
- CHRPE
- Congenital hypertrophy of the retinal pigment epithelium
20
Q
Attenuated FAP
A
- 3-99 adenomas in the colorectum
- Milder and may be later onset than regular FAP
21
Q
FAP-related gene
A
- APC
22
Q
MUTYH-associated Polyposis
A
- Autosomal Recessive
- 20-100 adenomas in the colorectum
- Can have symptoms associated with Gardner
- Osteomas
- CHRPE
23
Q
MAP-associated cancers
A
- Colon
- Ovarian
- Bladder
- Skin
- Duodenal
24
Q
Juvenile Polyposis Syndrome
A
- 3-5 juvenile polyps in the colorectum or GI tract
- Caused by mutations in SMAD4 and BMPR1A
25
JPS-associated cancers
* Colon
* Stomach
* Pancreatic
* Small bowel
26
Hyperplastic Polyposis Syndrome
* BRAF mutations associated with multiple, small left-sided polyps
* KRAS mutations associated with large right-sided polyps
* Increased risk for colon cancer
27
Peutz-Jeghers Syndrome - Cancers
* Pancreatic
* Esophageal
* Colon
* Stomach
* Breast
* Ovarian
* Lung
* Small bowels
28
Peutz-Jeghers Syndrome
* STK11 gene
* Hamartomatous polyposis of the GI tract
* Mucocutaneous pigmentation of the lips
29
Gorlin Syndrome/NBCCS
* Nevoid basal-cell carcinoma syndrome
* PITCH1, SUFU genes
* Distinct facies
* Frontal bossing, coarse facial features, facial milia, skeletal anomalies
* Cardiac and ovarian fibromas
* Multiple jaw keratocysts
* Cancers
* Basal cell carcinoma
* Pituitary NeuroectodermalTumors (PNET) - Medulloblastoma
30
Paragangliomas
* Tumor of the sympathetic nervous system
* Commonly found on the head, neck, and trunk
* 97% are benign and will not metastasize
31
Pheochromocytomas
* Secretory tumors of the medulla and adrenal glands
* Often oversecretion of catecholamines
32
PGL/PCC physical features
(symptoms of oversecretion of catecholamines)
* Persistent high blood pressure
* Headache
* Episodic profuse sweating
* Palpitations
* Pallor
* Anxiety
33
PGL/PCC genes
* SDHA, SDHB, SDHC, SDHD, SDHAF2, MAX
* SDHD is maternally imprinted
34
Birt-Hogge-Dubé - Cancers
* Chromophobe renal cell carcinoma
* Colon
35
BHD Skin Findings
* Fibrofolliculomas
* Trichodiscomas
* Perifollicular fibromas
36
BHD - other symptoms
* Spontaneous pneumothorax
* Renal cysts
* Lung cysts
* Thyroid nodules/cysts
37
BHD gene
* *FLCN*
38
Von-Hippel-Lindau tumors
* Renal cell carcinoma
* CNS and retinal hemangioblastoma
* Pheochromocytoma
* Paraganglioma
* Endolymphatic sac tumor
* Pancreatic
Renal cysts
39
Von-Hippel-Lindau gene
* VHL
40
MEN Type 1 Cancers
* Parathyroid
* Pituitary
* Pancreatic
* Adrenocortical
41
MEN Type 1 non-endocrine tumors
* Angiofibromas
* Collagenomas
* Lipomas
* Meningiomas
* Leiomyomas
42
MEN Type 1 Gene
* MEN1
43
MEN Type 2a Cancers
* Medullary thyroid
* Pheochromocytoma
* Parathyroid adenoma
44
MEN Type 2B
* Medullary thyroid cancer (onset in early childhood)
* Marfanoid habitus
* Lip and tongue mucosal neuromas
* Medullated corneal nerve fibers
45
Familial Medullary Thyroid Carcinoma
| (FMTC)
* Medullary thyroid cancer (later onset than MEN2)
* Absence of PGL/PCC
46
Hirshprung's Disease
* Megacolon
* Constipation
* Absence of neural ganglion cells from intestinal tract
* Typically restricted to rectosigmoid
* "Short-segment disease"
47
RET gene mutations
* MEN2A
* MEN2B
* FMTC
* Hirshprung's disease
48
Tuberous Sclerosis Complex Tumors
* Brain
* Astrocytoma
* Cortical tubers
* Sub-ependymal nodules in ventricles
* Neuroendocrine tumors
* Pituitary adenoma
* Parathyroid adenoma
* Pancreatic adenoma
49
TSC skin findings
* Shagreen patches
* Hypomelanotic patches
* Ungual fibromas
* Angiofibromas
50
TSC additional findings
* Cardiac rhabdomyomas
* Retinal nodular hamartomas
* Retinal achromic patch
* Cortical dysplasia
* Renal cysts
51
TSC genes
* TSC1
* TSC2
52
Carney Complex Tumors
* Thyroid
* Testicular - sertoli cell
* Breast - ductal adenoma
* Endocrine tumors
53
Carney Complex - Other findings
* Spotty skin pigmentation
* Mucosal pigmentation
* Myxomas - cardiac, breast, bone
* Psammomatous melanotic schwannoma
* Blue nevi
* Acromegaly secondary to growth-hormone producing adenomas
54
Carney Complex Genes
* PRKAR1A
