Monica Alverez-Cancer Genetics

Front 1

in cancer genetics is family history in mom or dad more important?

Back 1

fathers side of family is just as important as mothers

Front 2

what percentage of cancer is hereditary?

Back 2

5%-10%

Front 3

what percentage of patients who have personal/family history of cancer are referred for genetic counseling?

Back 3

5%-7%

Front 4

What tools do clinitians need to ID patients who need genetic counceling?

Back 4

1) ID high risk family histories
2) recognizing morphological/ histological features
3)access to resources

Front 5

genetic vs. inherited?

Back 5

cancer is always genetic but rarely inherited

Front 6

germline mutations

Back 6

present in egg or sperm
inheritable
cause cancer family syndromes

Front 7

somatic mutations

Back 7

occur in nongermline tissues
nonheritable

Front 8

Taking family history

Back 8

3 generation pedigree
all individuals on both sides of family and record
-age at cancer diagnosis
& age of dealth
-primary vs metastatic
cancer
-precursor lesions,
bilateral cancer
Record ethnicity & Race
Verify family history

Front 9

pedigree signs
1)male
2)female
3) death
4)affected
5)proband

Back 9

1)square
2)circle
3)slashed
4)shaded
5)arrow

Front 10

Hereditary Cancer

Back 10

-cancer in 2 or more close reletives on same side of family
-early age at diagnosis
-multiple primary tumors
-bilateral or multiple rare cancers
-constellation of tumors consistent w/ specific caner syndrome (e.g., breast & ovary, colon & endometrium
-evidence of autosomal dominant transmission

Front 11

autosomal dominant inheritance

Back 11

-each child has 50% chance of inheriting the mutation
-no "skipped generations"
-equally transmitted by men & women

Front 12

elements of cancer genetics evaluation

Back 12

-risk assessment
-education & counseling
-psychosocial assessment
-informed conssent
-genetic testing
-result intermpretation
-risk management plan

Front 13

T or F: Begnin by testing affected reletive of proband

Back 13

T

Front 14

Genes associate w/ cancer predisposition

Back 14

Tumor suppressor genes
- cells breaks for tumor
growth
- cancer arises when both
braks fail
DNA damage-response genes
- the repair mechanisms
for DNA
- Cancer arises when both
genes fail, speeding the
accumulation of
mutations in other
critical genes
Oncogenes
- accelerates cell
division
- cancer arises when
stuck on mode

Front 15

Genes implicated in hereditary breast cancer

Back 15

BRCA1-br, ovar, prost, etc
BRCA2- br, ovar, pancreas,etc
Li-Fraumeni
AT
Cowden

Front 16

BRCA1

Back 16

-1/500 women carriers
-mutations scattered through out gene
-breast tumors EstrogenReceptor neg(unusual)
-male carriers can pass gene on
-specific alterations in Ashkenazi Jewish individuals

Front 17

percentage of women who will get breast cancer

Back 17

8% (1/12)

Front 18

Inherited risk of cancer if have BRCA1

Back 18

1-45%

Front 19

strongest indicator of BRCA1 carrier

Back 19

breast & ovarian in same person

Front 20

Inherited risk of cancer if have BRCA1

Back 20

2-35%

Front 21

BRCA2

Back 21

-gene 2ce as big as BRCA1
-breast tumors ER+
-age of br cancer tends to be older
-wider spectrum of cancer types
-specific alterations in Ashkenazi Jewish individuals
-more likely to have affected male in pop.

Front 22

Ashkenazi Jewish Individuals

Back 22

-1/40 have mutation in BRCA1/2 regardless of family history
-founder effect (3 mutations accont for majority of carriers)

Front 23

option for BRCA mutation +

Back 23

-lifestyle changes
-increased surveillance
-prophilactic surgery
-chemo prevention

Front 24

Surveillance for BRCA1/2 mutation cancer

Back 24

Br cancer: 25-30 y/o
-annual mammo
-MRI
-ductal lavage
Ovarian cancer: 25-30 y/o
-TVU(transvaginal ultrasound)
-pelvic exam
-CA125 q6-12 mo (gene marker)
Colorectal Cancer: begin @40
Prostate Cancer: begin @ 40

Front 25

BRCA1/2 Key points

Back 25

-only 5%-10% of b/o cancer is inherited
-BRCA 1/2 are most common genes involved in inherited br/ov cancer susceptibility
- not all HBOC genes
known, family may still
be high risk even if
no mutation is found
- Mutations in BRCA1/2
- can be passed down by mom or dad
- more freequent in Ashkenazi Jewish families
- inherited in autosomal dominant fashion
-genetic testing can ID mutations in BRCA 1/2 & influence risk management
- risk reducing surgery should be offered to carriers

Front 26

colorectal cancer

Back 26

-2rd most common cancer in US
-most develop from polyps
-screening can prevent
-effets men & women equally
-diet & excercise big factor
-no BBQ meat
-60% sporadic/30% familial (clusters in family)

Front 27

Percent of cancers inherited?

Back 27

5%

Front 28

risk increases for colorectal cancer?

Back 28

number of effected relatives & earlier age of onset of cancer

Front 29

HNPCC clinical charististics

Back 29

-5% of colorectal cancer
-earlier age of onset(<45y/o)
-defects in 1 of 5 mismatch
repair genes
-tumors tend to be R sided
-improved survival vs other cancers

Front 30

HNPCC cancer risks

Back 30

colorectal
endometrial
ovary
stomach other (GU,GI, brain)

Front 31

HNPCC increases risk of second cancer T/F

Back 31

T

Front 32

HNPCC Fast Facts

Back 32

-known as lynch syndrome
-2-7% annual world wide insidence of colorectal cancer
-autosomal dominant inheritance
-40-60% pts test + for mutation
-extra colonic cancer risks gender specific
-CRC risk higher in males than females

Front 33

genes responsible for HNPCC

Back 33

mismatch repair (MMR) genes

Front 34

Microsatellite Instibility is found in what cancer

Back 34

HNPCC (95%)

Front 35

Surveilance for HNPCC carriers
1) colorectal cancer
2) endometrial cancer

Back 35

1) Colonoscopy -begin 20-25 reapeat every 1-2 yrs, anual at 20
2) Transvaginal ultrasound - begin 25-30 anually

Front 36

recommendation guidelines for HNPCC screening

Back 36

1) Amsterdam
2) Bethesda

Front 37

HNPCC: key points

Back 37

most common form of heridetary CRC
-uterine/endometrial cancer 2nd most common after CRC in HNPCC families
- polyp number not increased above gen. populations
-family/personal history and MSI/IHC can help ID affected individauls
-genetic testing in HNPCC can ID mutation carriers
-colonoscopy survelance can improve survival in at risk individauls
-bnefits of surveilance for most extracolonic cnacers are still unknown
-noncarriers can be spared anxiety and the need for increased surveilance

Front 38

Familial Adenomatous Polyposis(FAP)

Back 38

-early onset CRC - 35 yo
-significant # polyps
-A.D.
-tumor supressor gene
-~100% CRC penetrance by age 40
-30% arise from new mutation
-CHIRPE may be present (retina freckels)

Front 39

Garners Syndrome

Back 39

-Varient of FAP
-dental abnormalities
-benighn sist
-ST tumors

Front 40

FAP: Key pts

Back 40

-AD, early onsit
-30% no family hx
-many polips
-risk 100% w/out treatment
-genetic testing of children has medical benefit

Front 41

Factors that suggest inherited susceptibility

Back 41

-early onset
-more than one primary site
-bilatral disease
-close reletives w/ same related cancer
-rare presentations (e.g., male breast cancer)
-AD