Week 4: Cancer Genetics Flashcards
What is the purpose of oncotype Dx?
Recurrence score generated to determine the benefit of chemotherapy
Which models can be used for a risk assessment for breast cancer
Gail and Claus model
What are some Prior Probability models
BOADICEA, Tyrer-Cuzik, BRCAPro
What does the Gail model include in it’s assessment
Age, reproductive history, benign breast disease history, breast cancer in mother/sisters
What does the Claus model include in it’s assessment
family history of breast cancer
What does the Gail model not include in its assessment
Non-breast cancers, SDR, paternal history, age at dx in relatives
What does the Claus model not include in it’s assessment
Can’t put in all types of relationships- need to adjust; doesn’t include reproductive history etc
In the setting of a known mutation, what testing should be given to AJ patients
All 3 founder mutations!
Lifetime risk of breast cancer with BRCA1/2 mutations
50-80%
Lifetime risk of ovarian cancer in BRCA1 carrier
30-45%
Lifetime risk of ovarian cancer in BRCA2 carrier
10-20%
Breast screening for BRCA1/2 mutation carriers
Mammogram and breast MRI annually
Aromatase inhibitors can only be used in what women?
Post-menopausal
Tamoxifen must be used for how long to help reduce the risk of a second breast cancer
5 years
Prominent tumors in BRCA1/2 Carriers
Breast, Ovarian, prostate
Prominent tumors in LFS
Breast, Brain, ACC, Sarcoma
Lifetime risk of cancer with LFS in women and men
90%; 75%
Prominent tumors in Cowden Syndrome
Breast, Thyroid, Uterine
Lifetime risk of breast cancer in Cowden
25-50%
What is the skin triad observed in Cowden Syndrome
Trichilemmomas and papillomataous papules, sacral keratoses, mucocutaneous neuromas
Gene for LFS
TP53
Gene for HBOC
BRCA1/2
Gene for Cowden Syndrome
PTEN
Prominent cancer risk with CHEK2 mutation
Breast
Prominent tumor risk in PALB2
Breast, Pancreas
Prominent tumor risk in ATM heterozygotes
Breast
Genes in Lynch Syndrome
MLH1, MSH2, MSH6, PMS2, EPCAM
Lifetime risk for CRC with Lynch syndrome
70%
Colonoscopy and Upper Endoscopy for Lynch syndrome- starting age and frequency
20-25; every 1-2 years
Definition of HNPCC
Families that meet Amsterdam criteria
Definition of Lynch Syndrome
Families with gremlin MMR gene mutations
Definition of Familial Colon Cancer Syndrome X
HNPCC families without a germline MMR mutation or phenotype of Lynch
Muir Torre Syndrome
HNPCC features with sebaceous carcinomas and Keratocanthomas
Turcot Syndrome
MMR mutations associated with glioblastoma ; APC mutations associated with medullablastoma
Amsterdam Criteria
3 or more relatives with CRC in the family (one FDR of other 2); 2 or more generations affected; 1 CRC by age 50
What percent of Lynch syndrome tumors have MSI
95%
What percent of sporadic tumors have MSI
10-15%
Gene for FAP
APC
Prominent tumor in FAP
CRC
Lifetime risk of CRC in FAP
100%
Colonoscopy and Endoscopy starting at what age and frequency in FAP
10-12; every 12 months
Gardener’s Syndrome
Desmoid tumors and osteomas; supernumerary teeth; CHRPE; soft tissue skin tumors
Gene for MYH-Associated Polyposis
MUTYH