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Genetic Counseling Flashcards > Cancer Genetics > Flashcards

Cancer Genetics Flashcards

1
Q

Lynch syndrome

A
  • MSH2, MLH1, PMS2, MSH6, EPCAM (mismatch repair genes, responsible for 38%, 32%, 15%, and 14%, and 1-3% of LS cases respectively)
  • Increased risk for (%):
    • Endometrial cancer: 28-60
    • CRC: 30-80 (M at higher risk)
    • Gastric: 5-13
    • Ovarian: 4-38
    • Small bowel: 3-6
    • Upper urinary tract: 8.4
    • CNS: 4
    • Biliary tract: 2-18
    • Breast: 0-13
    • Sebaceous gland neoplasms: 1-9
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2
Q

IHC

A

immunohistochemistry (tumor analysis) of the MMR proteins

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3
Q

MSI

A
  • Microsatellite instability analysis (tumor analysis)
  • Found in 15% of CRCs
  • MSI-H (high MSI) may indicate Lynch syndrome
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4
Q

hereditary vs. familial vs. sporadic

A
  • hereditary 5-10%
  • familial 15-25% (due to shared env. or unknown genetic variants)
  • sporadic 65-80%
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5
Q

Gen pop baseline lifetime risks

A
  • CRC: 5-6%
  • Uterine: 2-3%
  • Breast and prostate: ~12%
  • Ovarian: 1%
  • Panc: 1.5%
  • Bladder: 2.5%
  • Gastric, small bowel, urothelial, CNS: <1%
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6
Q

risk calculation models - HBOC

A
  • BRCAPro (lifetime risk)
  • Tyler-Cuzick (lifetime risk)
  • BODICEA (lifetime risk)
  • Gail (5 yr risk)
  • Claus (5 yr risk?)
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7
Q

risk calculation models - Lynch syndrome

A
  • MMRpredict
  • Leiden
  • MMRPro
  • PREMM
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8
Q

BRAF and MLH1 hypermethylation testing

A
  • hypermethylation of MLH1 and somatic mutations of BRAF
  • Indicate a sporadic, NON-LS CRC/endo cancer
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9
Q

Familial adenomatous polyposis

A
  • APC; AD
  • Genetic testing criteria: >10 polyps in lifetime?
  • Increased cancer risks (%):
    • CRC:
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10
Q

Li-Fraumeni syndrome

A
  • TP53 (“guardian of the genome”); AD
  • Predisposition to all cancers (90% lifetime risk), esp. breast cancer
  • Remember the B’s: Bone, Brain, Blood, Breast! (%):
    • Breast: 28
    • Soft tissue: 14
    • Brain: 13
    • Adrenal gland: 11
    • Bone: 8
  • Must do skin punch biopsy for confirmatory testing.
  • Mgmt:
    • Exams every 6-12 months >20yr old
    • 20-29 annual breast MRI, discuss RRM
    • 30-75: annual breast MRI, consider tomosynthesis and RRM
    • Colonoscopy every 2-5 yrs >25yrs old
    • Annual derm exam
    • Annual whole body and brain MRI
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11
Q

chronic myelogenous leukemia

A
  • somatic, not inherited
  • Caused by Philadephia chromosomes (fusion of chr9 and chr22, specifically BCR-ABL1)
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12
Q

Fanconi anemia

A
  • BRCA2; AR
  • Also associated with other genes (E.g., FANC genes, PALB2, RAD51C, BRIP1, SLX4)
  • Age of onset 6-8yrs
  • Bone marrow failure, organ defects, CALMs, short stature
  • Increased cancer risk:
    • 10-30% risk for AML (acute myeloid leukemia) or tumors (head, neck, skin, GI, GU)
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13
Q

PALB2

A
  • PALB2; AD
  • Increased cancer risks (%):
    • F breast cancer risk: 33-58?/84?
    • Increased M br. cancer, panc, ovarian, prostate
  • Mgmt:
    • Annual mammo, consideration of tamoxifen and MRI >30yo
    • RRM- NO, unless fam hx is risky
    • Counsel about Fanconi risk if both parents are carriers
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14
Q

Hereditary diffuse gastric cancer syndrome

A
  • CDH1; AD
  • Diffuse gastric cancer: 56-83%
  • F breast cancer risk: 39-52% (lobular only)
  • Mgmt:
    • Gastrectomy between age 18 and 41
    • Can consider UGI with biopsies every 6-12 months
    • >30yo: annual mammo/MRI with consideration of tamoxifen
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15
Q

Peutz-Jeghers Syndrome

A
  • STK11; AD
  • Hamartomas, derm signs (freckling in childhood), GI pain/anemia from GI bleeding
  • Risks (%):
    • Lifetime risk of all cancers: 93%
    • CRC: 40
    • Breast: 30-50
    • Panc: 11-36
    • Stomach: 29
    • Small bowel: 13
    • Lung cancer
    • Gyn cancers
      • Ovarian: 20 (often sex-cord tumors with annular tubules)
      • Cervical cancer: 10
      • Uterine: <10
  • Mgmt:
    • Mammo and breast MRI 6 months >25yo
    • Colonoscopy and UGI every 2-3y in late teens
    • Small bowel visualization
    • Many more….
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16
Q

ATM

A
  • ATM; AD
  • Increased risk for cancer:
    • Risk or F br. cancer: 2-4x
    • Ovarian+
  • Mgmt:
    • Annual mammo >40yo, consider tomosynth and breast MRI
    • No RRM
    • Ataxia telangiectasia risk if other parent is carrier
      • Increased risk for lymphoma and leukemia, and breast cancer
      • Telangiectasias, progressive loss of ability to walk and talk, choreoathetosis, hypersensitive to ionizing rad.
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17
Q

CHEK2

A
  • CHEK2; AD
  • F breast cancer: 2x risk
  • Increased colon risk
  • Mgmt:
    • Annual mammo and colonoscopy >40yr, consider tamoxifen/breast MRI
    • No RRM
    • Low penetrance mutation Ile157Thr
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18
Q

Neurofibromatosis 1

A
  • NF1; AD
  • F breast cancer risk: 3-5x
  • Increased risk for:
    • Brain tumors
    • Leukemia
    • GIST (gastrointestinal stromal)
    • Parangangliomas and pheochromocytomas
  • Mgmt:
    • Annual mammo and breast MRI >30yr, consider tamoxifen and breast MRI
    • No RRM
    • Refer to NF1 specialist for further eval for CALMs, Lisch nodules, inguinal freckling, neurofibromas, skeletal dysplasia, LD
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19
Q

BARD1 and MRE11A

A
  • AD
  • Increased risk for breast and ovarian cancer
  • No mgmt recommendations currently
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20
Q

BRIP1, RAD51C/D and RAD50

A
  • AD
  • Increased risk for F breast cancer, ovarian (9% for BRIP1)
  • Consider RRSO at 45-50yo
  • Counsel about Fanconi anemia risk
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21
Q

NBN

A
  • AD
  • Increased risk for F and M breast cancer, prostate, medulloblastoma, and CNS tumors
  • Mgmt:
    • Annual mammo >40yo, consider tamoxifen and breast MRI
    • No RRM
    • Counsel about Nijmegen breakage syndrome
22
Q

Small breast cancer panel

A

ATM, BRCA1/2, CDH1, CHEK2, PALB2, PTEN, TP53

23
Q

Medium breast cancer panel

A

ATM, BRCA1/2, CDH1, CHEK2, PALB2, PTEN, TP53 plus: BARD1, BRIP1, MRE11A, MUTYH, NBN, NF1, RAD50, RAD51C, RAD51D

24
Q

hereditary paragangliomas

A
  • SDHD; AD
  • Low malignancy rate
  • Tumors in ganglia, pheochromocytoma (PGL and PCC)
  • Example of imprinting - only affected if inherited from father
25
Q

Retinoblastoma

A
  • RB1 ; AD
  • 1 in 13,500-20,000
  • Leukoria, strabismus
  • Two-hit hypothesis example because age of onset is infancy
  • Subtypes: 13q deletion syndrome, low penetrant RB
  • 40% of cases are hereditary; penetrance is high
  • Clinical dx criteria: Bilateral or trilateral; OR Unilateral with fam hx
26
Q

HBOC

A

Hereditary Breast and Ovarian Cancer Syndrome

  • Ask pt. about:
    • Reproductive factors: age at menses, gravida/para, breastfeeding, HRT, contraceptive use, menopause
    • Cancer screenings and personal cancer history: ovarian cancer screenings, colonoscopies, etc., mammograms, tumor biopsy results, etc.
  • Types of results, and what they could mean for medical management
    • Positive
      1. Alternate MRI/mammogram screenings every 6 months beginning at 25 years old.
      2. Tamoxifen chemoprevention
      3. Possibility of preventative mastectomy
      4. Consideration of ovarian cancer screening beginning at 30 years old (annual or semiannual transvaginal ultrasound and serum CA-125)
      5. Bilateral oophorectomy after finished childbearing
    • Variant of Uncertain Significance
      1. No changes in medical management, unless family history is still suggestive of a familial HBOC syndrome, then follow moderate risk guidelines:
        1. Consideration of mammography at 35 years old. (>20% lifetime risk)
        2. Tamoxifen chemoprevention (>1.7% 5 year risk)
        3. Oral contraceptives
    • Negative
      1. No changes in medical management, unless family history is still suggestive of a familial HBOC syndrome (>20% lifetime risk from Claus, BRCAPRO, Tyler-Cuzick and BOADICEA), then follow moderate risk guidelines:
        1. Consideration of mammography at 35 years old. (>20% lifetime risk)
        2. Tamoxifen chemoprevention (>1.7% 5 year risk)
        3. Oral contraceptives
27
Q

BRCA1

A
  • Increases cancer risks (%):
    • F. breast: 46-87
    • Ov: 39-63
    • Panc+
    • Prostate: up to 16
    • M. breast: 1.2
28
Q

BRCA2

A
  • AR carries Fanconi Anemia risk.
  • Increases cancer risks (%):
    • F. breast: 42-84
    • Ovarian: 16.5-27
    • Panc: 7
    • Prostate: 20
    • M breast: 6.8
29
Q

MSH6

A
  • Lynch (7-10% of cases; less severe phenotype).
  • Increased cancer risks (%):
    • CRC: 10-22 (NCCN: 15-44)
    • Uterine: 17-46
    • Ovarian: 1-11
30
Q

PMS2

A
  • Lynch
  • Increased cancer risks (%):
    • CRC: 15-20
    • Uterine 0-15
31
Q

EPCAM/TACSTD1

32
Q

MLH1

A
  • Lynch (50% of cases)
  • Increased cancer risks (%):
    • CRC: 22-74 (NCCN: 46-49)
    • Uterine: 43-57
    • Ovarian: 5-20
    • Breast: 12-17
    • Panc: 6
    • Gastric: 5-7
33
Q

MSH2

A
  • Lynch (40% of cases).
  • Increased cancer risks (%):
    • CRC: 22-74 (NCCN: 43-52)
    • Uterine: 21-57
    • Ovarian: 10-38
    • Gastric: 0.2-16
    • Bladder: 4-17
    • Urothelial: 2-18
    • Small bowel: 1-10
    • Prostate: 30-32
34
Q

APC

A
  • FAP - adenomatous CRC risk.
  • Signs:
    • Osteomas, missing/extra teeth, CHRPE, skin cysts and fibromas, adrenal masses
  • Increased cancer risks (%):
    • CRC: 100
    • Increased risks for small bowel, panc, thyroid, CNS, liver, stomach, and bile duct
  • Mgmt: Colectomy possible
35
Q

MUTYH

A
  • AR.
  • MYH-Associated polyposis (MAP) - adenomatous CRC risk.
  • Signs:
    • Thyroid nodules, benign adrenal lesions, jawbone cysts, CHRPE.
  • Increased cancer risks (%):
    • CRC: 80-90
    • Increased risks for duodenal, ovarian, thyroid, breast, gastric, skin, and endometrial
36
Q

RNF43

A
  • Serrated polyposis syndrome - adenomatous
  • Undefined risk for CRC
37
Q

BMPR1A, SMAD4

A
  • Juvenile polyposis syndrome (onset 15yo)
  • Signs:
    • Anemia, BM issues
    • Can lead to hereditary hemorrhagic telangiectasia
  • Increased cancer risks (%):
    • CRC: 40-50
    • Stomach: 21
38
Q

Von Hippel Lindau

A
  • VHL; AD
  • 70% risk of RCC
  • Signs:
    • Pancreatic and renal cysts
  • Increased cancer risks:
    • Hemangioblastomas in brain & spinal cord
    • Neuroendocrine tumors
    • Pheos and paragangliomas
    • Endolymphatic sac tumors and retinal angiomas
  • . Highly penetrant
39
Q

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC)

A
  • FH; AD
  • FH deficiency if homozygous
  • Increased cancer risk:
    • Cutaneous & uterine leiomyomas
    • Renal tumors
    • 10-30% risk for RCC
  • Highly penetrant
  • Mgmt:
    • Skin exam 1-2 years, yearly gynecologic exam, yearly abdominal MRI.
    • cutaneous lesions - surgical excision, meds.
    • Uterine fibroids - meds, surgical excision.
    • Renal tumors - surgery, total nephrectomy considered, meds.
40
Q

Multiple Endocrine Neoplasia Type 1 (MEN1)

A
  • MEN1; AD
  • Signs:
    • Hyperparathyroidism, skin findings (facial angiofibromas, collagenomas, CALMs, etc.)
  • Increased cancer risks:
    • pituitary tumors
    • pancreatic/duodenal NETs
    • carcinoid tumors
    • ACC
  • Dx criteria: 2 of the 3 P’s:
    • parathyroid
    • pituitary
    • panc
41
Q

Multiple Endocrine Neoplasia Type 2 (MEN2) and FMTC

A
  • RET; AD
  • 3 subtypes:
    • MEN2A: MTC, PCC, parathyroid disease
    • MEN2B (most aggressive, can have cancer as a child): MTC, PCC, Marfanoid habitus and distinctive facies
    • FMTC: MTC and PTC
  • Signs:
    • distinct facial appearance (FMTC), parathyroidism, ganglioneuromatosis of GI tract, PCCs
  • Increased cancer risk (%):
    • Medullary thyroid carcinoma: 95-100
42
Q

Bloom Syndrome

A
  • BLM; AR.
  • Signs:
    • Growth deficient, skin findings, diabetes, butterfly rash, skin sensitivity
  • Increased cancer risk:
    • Lymphomas, leukemias, WT, other rare childhood cancers
43
Q

Xeroderma pigmentosum

A
  • XP; AR
  • Signs:
    • Severe sunlight sensitivity, hyper and hypopigmentation, progressive neurological abnomalities.
  • Increased cancer risk:
    • High risk for BCC, melanoma, and SCC
44
Q

Tuberous Sclerosis

A
  • TSC1, TSC2; AD
  • Signs:
    • CNS tumors, seizures, TAND, DD/ID, renal cyst, benign angiomyolipomas, NETS, retinal hamartomas, cardiac rhabdomyomas
  • Increased cancer risk:
    • 80% have renal malignancy by age 10
    • RCC risk+
    • Malignant angiomyolipomas.
  • 100% penetrance w/ variable expressivity.
45
Q

Hereditary Melanoma

A
  • CDK2NA, CDK4, BAP1, MITF; AD
  • Increased cancer risk:
    • Malignant melanoma usually dx <50 w/ multiple primaries
    • Rare neural tumors
    • Panc+, ocular melanoma+
  • High penetrance.
  • BAP1 specifics:
    • dermal lesions.
    • Increased cancer risk (%):
      • ocular melanoma: 31
      • cutaneous melanoma: 13
      • renal: 10
      • mesothelioma: 22
  • MITF specifics:
    • Renal+
    • Intermediate penetrance
46
Q

Venoid Basal Cell Carcinoma

A
  • PTCHI, SUFU; AD
  • Signs:
    • Cardiac and ov fibromas, Macrocephaly, polydacytly, motor delay, skeletal malformations and eye anomalies
  • Increased cancer risk (%):
    • BCC: 90
    • Medulloblastoma: 5
47
Q

Cowden syndrome

A
  • PTEN, SDHB, SDHD, KLLN; AD
  • PTEN is tumor suppressor
  • Similar to Bannayan-Riley-Ruvalcaba syndromeand Proteus syndrome, sometimes together referred to as “PTEN hamartoma tumor syndrome”
  • Overgrowth syndrome
  • Signs:
    • Macrocephaly: “PTEN BIG HEAD”
    • Hamartomas (nearly 100% chance)
    • Derm signs (e.g., trichilemmomas, pic)
    • Sometimes: Lhermitte-Duclos (rare, noncancerous brain tumor), ID/DD
  • Increased cancer risk (%):
    • Breast: 50-85
    • Thyroid: 30-40
    • Uterine: 25-30
    • CRC: 5-10
    • Kidney: 30-35
    • Melanoma: 6
48
Q

Weaver syndrome

A
  • EZH2; AD
  • Overgrowth syndrome
  • Tall stature, sometimes macrocephaly, mild ID, broad forehead, hypertelorism, joint contractures, hypo/hypertonia
  • Increased risk for neuroblastoma in early childhood (exact % unknown)
49
Q

Beckwidth-Wiedmann syndrome

A
  • Abn methylation at 11p15.5 imprinting centers (IGF2, CDKN1C, &more); 85% de novo due to imprinting, 15% AD due to point mutations
  • Most cases caused by paternal UPD
  • Overgrowth syndrome
  • Signs:
    • Macroglossia
    • Macrosomia
    • Hemihypertrophy
    • Omphalocele
    • Hypoglycemia
    • Wilm’s tumor
  • Increased cancer risk in childhood (before age 10):
    • 5-10% overall
    • Embryonal tumors:
      • Wilm’s tumor (40% of cases)
      • Hepatoblastoma
      • Neuroblastoma
      • Rhabdomyosarcoma
    • Adrenocortical tumor (20% of cases)
50
Q

Werner Syndrome

A
  • WRN; AR
  • Signs:
    • Premature aging w/ short stature and malignancies typically developing between 25 and 64.
  • Increased Cancer Risk (%):
    • Thyroid: 16
    • Melanoma: 13
    • Meningioma: 11
    • Soft tissue sarcoma: 10
    • Leukemia: 9
    • Osteosarcoma: 8
  • Mgmt:
    • Surveillance: Type 2 DM screening, yearly physical exam, skin exams.
    • Trx skin ulcers, DM control, trx of cancer following typical guidelines.
51
Q

Carney Complex

A
  • PRKAR1A; AD
  • Signs:
    • Skin abnormalities (multiple lentigines and blue nevi on eyes, ears, lips, genitals), myxomas (esp. dangerous in heart), endrocrine disruption, psammomatous melanotic schwannomas
  • Increased cancer risk (%):
    • 10% risk for cancer
    • 10% risk of PMS becoming malignant
  • Mgmt:
    • Surveillance: biannual echo, thyroid US, testicular US, transabdominal US, IGF-1 and cortisol level, adrenal CT.
    • Trx: Sugical intervention of trx with meds for tumors.
52
Q

Birt-Hogg-Dube syndrome

A
  • FLCN; AD
  • Signs:
    • Fibrofolliculoma, skin tags, pulmonary cysts, pneumothorax
  • Increased cancer risk (%):
    • RCC: 20-30
  • Mgmt:
    • Surveillance: skin exam, lung CT, annual abdominal MRI/CT.

Genetic Counseling Flashcards (22 decks)

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