Genetic Risk Factors

Question 1

5 mutations seen in Lynch syndrome

Answer 1

MMR genes
MLH1, MSH2, MSH6, PSM2, EPCAM deletions

Question 2

Lynch syndrome will have what finding on IHC path reports in >90% of cases?

Answer 2

MSI-H or dMMR

Question 3

Cancers assocaited with lynch styndrome

Answer 3

Colon (45-60% lifetime risk)
Endometrial (20-55%)
Prostate
Ovarian
Urothelial
Gastric
Small bowel
pancreatic
sebaceous skin tumors

Question 4

What genes within Lynch have lower cancer risk?

Answer 4

PMS2
MSH6

Question 5

What is Muir-Torre syndrome?

Answer 5

Sebaceous skin tumors seen in Lynch syndrome

Question 6

Are all colorectal cancers that are MSI-H due to lynch syndrome?

Answer 6

No. 10-15% is sporadic

Question 7

Patient with CRC found to have absent MLH1, and BRAF V600E mutation. Is this Lynch syndrome or sporadic?

Answer 7

Sporadic cancer

Question 8

Patient with CRC has absent MLH1 and MLH1 promoter hypermethylation. Lynch syndrome or no?

Answer 8

No. Sporadic cancer

Question 9

When to screen for CRC in a lynch syndrome carrier?

Answer 9

Colonoscopy every 1-2 years at age 20-25 or 2-5 years prior to earliest CRC
Consider ASA for prophy

Question 10

Endometrial screening/risk reduction for Lynch syndrome carrier

Answer 10

Hysterectomy and BSO once child bearing complete, no discrete recommended time. Consider endometrial biopsy every 102 years at age 30-35

Question 11

Gastric/small bowel screening for Lynch syndrome carrier?

Answer 11

EGD Q2-4 years at age 30-40 w random gastric biopsies at initial procedure

Question 12

Urinary tract cancer screening for Lynch syndrome carriers

Answer 12

ONLY FOR MSH2 carriers: UA annually at age 30-35

Question 13

Lynch carriers with MSH6 or PMS2 mutations - how is their screening/management different?

Answer 13

Colonoscopies could begin age 30-35 (or 10 years younger than family member) since they have later onset cancer

Question 14

Inheritance and mutation of FAP

Answer 14

AD mutation in APC TSG on Chr5q

Question 15

5 Extraintestinal features of FAP

Answer 15

Desmoid tumors
Epidermoid or sebaceous cysts
Osteomas
Supernumery teeth
Congenital hypertrophy of retinal pigment epithelium

Question 16

What is attenuated FAP?

Answer 16

10-100 adenomas (instead of 1000s). Adenomas typically right sided. High CRC risk but not 100% like FAP

Question 17

FAP screening

Answer 17

Flex sig or colonoscopy annually starting at 10-15y

Question 18

How to manage adenomas seen in FAP?

Answer 18

Colectomy if a lot of adenomas, including high grade

Question 19

What is surveillance for patients with FAP who already had a colectomy?

Answer 19

Endoscopy of pouch or preserved rectum every 6-12 months

Question 20

Aside from colonoscopies, what other screening is needed for FAP carriers?

Answer 20

Upper endoscopy 20-25
Thyroid US baseline in teens then q2-5 yeras
CT or MRI annually if personal history of desmoid tumor

Question 21

MUTYH-associated polyposis inheritance

Answer 21

AR

Question 22

MUTYH-assocaited polyposis clinical features

Answer 22

10-100 adenomas, 2.9x risk of CRC for heteroz, 53x risk for homozygotes

Question 23

Screening/management of MUTYH-associated polyposis

Answer 23

Colonoscopy age 20-25 every 1-2 years
Colectomy with heavy polyp burden
Baseline upper endoscopy age 35

Question 24

Clinical features of Peutz-Jeghers Syndrome

Answer 24

GI hamartomas that are frond like
Mucocutaneous pigmentation in mouth, lips, nose, eyes, fingers
30-50% risk of breast cancer
40% risk of CRC cancer
30% risk of stomach
11-36% risk of pancreas
20% risk of ovarian sex cord tumors

Question 25

Mutation and inheritance of Peutz-Jeghers syndrome

Answer 25

STK11 gene, AD

Question 26

What syndrome is associated with mutation in STK11?

Answer 26

Peutz Jeghers

Question 27

Management of Peutz-Jeghers syndrome

Answer 27

Colonoscopy Q2-3 years and upper endoscopy at age 8-10 Pancreatic screening for all age 30-35

Question 28

If you have a patient with Peutz-Jeghers syndrome that develops breast cancer, how does that change their management?

Answer 28

Treat like BRCA1/2 mutation

Question 29

Mutations seen in Juvenile polyposis (2)

Answer 29

SMAD4 BMPR1A

Question 30

Which patients wiht pancreatic cancer should get germline testing?

Answer 30

Everyone

Question 31

What two mutations should you screen carriers for pancreatic cancer?

Answer 31

STK11 (age 30-35) CDKN2A (age 40)

Question 32

What syndrome is associated with PTEN mutation?

Answer 32

Cowden syndrome

Question 33

Inheritance of BRCA1/2

Answer 33

AD

Question 34

OVarian cancer is most common in BRCA1 or BRCA2?

Answer 34

MRCA1

Question 35

Cancers assocaited with BRCA1/2

Answer 35

Breast Ovarian (1>2) Prostate Pancreatic Stomach (2>1)

Question 36

Breast Screening for BRCA1/2 carreirs

Answer 36

Start age 18 Mammo yearly 30-75 MRI yearly 25-75 Breast exam Q6-12 mon age 25

Question 37

Ovarian screening for BRCA carriers

Answer 37

None

Question 38

Risk reductino for BRCA1/2 carriers

Answer 38

B/l mastectomy BSO age 35-40

Question 39

When is the optimal timing for BSO in BRCA carriers?

Answer 39

35-40 and childbearing complete BRCA2 can be delayed to 40-45

Question 40

Mangement of man with BRCA1/2

Answer 40

Breast Self exam age 35 PSA age 40 for BRCA2

Question 41

Most common receptor type of breast cancer in BRCA1?

Answer 41

TNBC

Question 42

Most common cancer seen in Li-Fraumeni?

Answer 42

Breast

Question 43

Breast cancer screening for Li-Fraumeni?

Answer 43

CBE 6-12 mon at age 20 MRI age 20-29 Mammo+MRI age 30-75 Consider risk reducing amstectomy

Question 44

Clinical features of Cowden syndrome

Answer 44

Pathognomonic mucocutaneous lesions (trichilemmomas, papillomatous papules) Macrocephaly Developmental delay Thyroid, endometrial, breast tumors/cancers

Question 45

Cancers associated with Cowden syndrome (3)

Answer 45

Thyroid Endometrial Breast

Question 46

VHL mutation is associated with what cancer?

Answer 46

ccRCC Hemangioblastomas, pheos

Question 47

TSC1, TSC2 gene is seen in what condidion? What tumors are associated?

Answer 47

Tuberous sclerosis ccRCC Angiomyolipomas in kidneys

Question 48

Spontaneous pneumothorax and a renal mass. What is the syndrome?

Answer 48

Birt-Hogg-Dube

Question 49

Features of MEN1

Answer 49

Parathyroid adenoma Pituitary adenoma Pancreatic islet cell tumor (gastrinoma, insulinoma, VIPoma)

Question 50

Features of MEN2A

Answer 50

Medullary thyroid Pheo Primary parathyroid hyperplasia

Question 51

Features of MEN2B

Answer 51

Medullary thyroid cancer Pheos Mucosal neuromas Marfanoid habitus

Question 52

Gene mutation associated with MEN syndromes

Answer 52

AD mutation in RET

Question 53

4 Cancers seen in FAP

Answer 53

Colon Small bowel Stomach Papillary thyroid

Question 54

Cancer syndrome associated with uveal melanoma, malignant mesothelioma, cutaneous melanoma, and RCC

Answer 54

BAP1

Question 55

Cancer gene mutation associated with pancreatic cancer, melanoma, and H&N SCC

Answer 55

CDKN2A

Question 56

PALB2 mutation increases likelihood of what 3 cancers

Answer 56

Breast Ovarian Pancreatic

Question 57

When to start PSA screening for men with BRCA2 mutations?

Answer 57

40

Question 58

What can be done to reduce risk of future cancers for women with RAD51C mutations?

Answer 58

BSO between age 45-50 No need for mastectomy

Question 59

How do colon cancer screening recommendations change for a patient with Lynch syndrome based on mutation?

Answer 59

MSH6: Start at 30-35 or 2-5 years prior to earliest colon cancer Others: Start at 20-25 or 2-5 years prior

Question 60

Breast cancer screening for woman with PALB2 mutation

Answer 60

Mammo and MRI annually at 30

Question 61

Patient with multiple atypical nevi throughout their body, always biopsied as benign. Has a family member with a history of pancreatic cancer. Gene that is implicated in this syndrome?

Answer 61

CDKN2A - familial atypical multiple mole melanoma syndrome