Genetic Predisposition to Cancer Flashcards Preview

Principles of Disease > Genetic Predisposition to Cancer > Flashcards

Flashcards in Genetic Predisposition to Cancer Deck (35):
1

What are somatic mutations?

Occur in nongermline tissues

2

What are germline mutations?

Mutations in germ cells - responsible for producing eggs and sperm. Heritable, cause cancer family syndromes

3

What is the function pf proto-oncogenes?

Codes for proteins that regulate cell growth and differentiation

4

What is an oncogene?

Mutated proto-oncogene

5

what is the effect of oncogenes?

Accelerate cell division

6

How many mutations of the chromosomes are needed before control of the cell cycle is lost in oncogenes?

1 mutation needs to occur

7

What is the function of tumour suppressor genes?

Slow down cell division
Repair DNA mistakes
Tell cells when to die (a process known as apoptosis or programmed cell death)

8

What is the function of DNA damage response genes?

The repair mechanics for DNA


Cancer arises when both genes fail, speeding the accumulation of mutations in other critical genes

9

What is the function of Mismatch repair genes?

MMR corrects errors that spontaneously occur during DNA replication like single base mismatches or short insertions and deletions

10

What does Micro satellite instability an indicator of?

Phenotypic evidence that MMR is not functioning normally.

Cells with abnormally functioning MMR tend to accumulate errors, simple sequence repeats are created

11

Give an example of a cancer syndrome associated with Oncogenes

MEN2 (Multiple endocrine neoplasia)
Familial medullary thyroid cancer

Can be caused by viruses

12

Give an example of a cancer syndrome associated with Tumour suppressor gene

Breast/ovarian cancer FAP Li-Fraumeni syndrome Retinoblastoma

13

Give an example of a cancer syndrome associated with DNA repair (mis-match repair)

HNPCC / Lynch Syndrome
(Hereditary non-polyposis colon cancer)

14

What are other causes of cancer?

Autosomal recessive syndromes
E.g. MYH polyposis

Multiple modifier genes of lower genetic risk

15

What is a De Novo mutation?

New (de novo) mutation occurs in germ cell of parent
No family history of hereditary cancer syndrome


A new mutation in a germ cell?

16

Describe cancer susceptibility genes

They are dominant with incomplete penetrance

17

Is heritable retinoblastoma usually bilateral or unilateral?

Usually bilateral

18

Does heritable retinoblastoma usually contain a family history?

Yes in 20 percent of cases

19

What are the risk factors of breast cancer?

Ageing, family history, Early menarche - first period, late menopause, Nulliparity -not having children
Estrogen use, dietary factors, lack of exercise.

20

What are the common genes responsible for breast cancer?

BRCA1
BRCA2
TP53
PTEN
Undiscovered genes

21

What is the function of BRCA1?

Checkpoint mediatorDNA damage signalling and repairChromatin remodelling (inactive X chromosome)Transcription (not essential for this)

(PROTEIN THAT ACTS AS A TUMOUR SUPPRESSOR)

22

What is the function of BRCA2?

DNA repair by HR (homologous recombination)

23

What are the BRCA1 associated cancers?

Breast cancers, second primary breast cancer

Ovarian cancer

24

What are the BRCA2 associated cancers?

Breast cancer, ovarian cancer, male breast cancer

Increased risk of prostate, laryngeal, and pancreatic cancers (magnitude unknown)

25

What are risk factors for colorectal cancers?

Ageing
Personal history of CRC or adenomas
High-fat, low-fibre diet
Inflammatory bowel disease
Family history of CRC

26

What is the sequence of events for Adenoma to carcinoma?

Epithelium becomes hyperactive, adenoma forms, carcinoma forms

27

How many adenomas are present in non-polyposis (Hereditary Colorectal Cancer (CRC) syndromes)

few to no adenomas

HNPCC (hereditary non-polyposis colon cancer / Lynch Syndrome) - CRC &/or endometrial cancer (EC

28

How many adenomas are present in polyposis (Hereditary Colorectal Cancer (CRC) syndromes)

(multiple adenomas)

FAP – severe colonic polyposis +/- CRC
AFAP - less severe colonic polyposis +/- CRC
MAP – varying degrees of colonic polyposis +/- CRC

FAP – familial adenomatous polyposis
AFAP – attenuated FAP
MAP – MYH associated polyposis

29

What are the clinical features of HNPCC

Early but variable age at CRC diagnosis (~45 years)
Tumor site throughout colon rather than descending colon
Extracolonic cancers: endometrium, ovary, stomach, urinary tract, small bowel, bile ducts, sebaceous skin tumors

30

What are clinical features of FAP?

Estimated penetrance for adenomas >90%
Risk of extracolonic tumors (upper GI, desmoid, osteoma, thyroid, brain, other)
CHRPE may be present
Untreated polyposis leads to 100% risk of cancer

31

Describe the effect of attenuated FAP

Later onset (CRC ~age 50)
Few colonic adenomas
Not associated with CHRPE
Upper GI lesions
Associated with mutations at 5' and 3' ends of APC gene

32

What condition is similar to attenuated FAP?

Recessive MYH polyposis

Common mutations in mut- MYH gene

33

What can Multiple modifier genes explain?

May explain families with history of cancer and no identified mutation

May explain differences in cancer penetrance in families with same mutation

34

How can you manage caner risk in Adenomatous Polyposis syndromes?

Surveillance
Surgery
Chemoprevention

35

What portion of cancers are due to inherited mutations?

Only a small portion