Genetic Predisposition to Cancer Flashcards

1
Q

What are somatic mutations?

A

Occur in nongermline tissues

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2
Q

What are germline mutations?

A

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

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3
Q

What is the function pf proto-oncogenes?

A

Codes for proteins that regulate cell growth and differentiation

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4
Q

What is an oncogene?

A

Mutated proto-oncogene

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5
Q

what is the effect of oncogenes?

A

Accelerate cell division

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6
Q

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

A

1 mutation needs to occur

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7
Q

What is the function of tumour suppressor genes?

A

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

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8
Q

What is the function of DNA damage response genes?

A

The repair mechanics for DNA

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

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9
Q

What is the function of Mismatch repair genes?

A

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

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10
Q

What does Micro satellite instability an indicator of?

A

Phenotypic evidence that MMR is not functioning normally.

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

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11
Q

Give an example of a cancer syndrome associated with Oncogenes

A

MEN2 (Multiple endocrine neoplasia)
Familial medullary thyroid cancer

Can be caused by viruses

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12
Q

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

A

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

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13
Q

What are other causes of cancer?

A

Autosomal recessive syndromes
E.g. MYH polyposis

Multiple modifier genes of lower genetic risk

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14
Q

What is a De Novo mutation?

A

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

A new mutation in a germ cell?

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15
Q

Describe cancer susceptibility genes

A

They are dominant with incomplete penetrance

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16
Q

Is heritable retinoblastoma usually bilateral or unilateral?

A

Usually bilateral

17
Q

Does heritable retinoblastoma usually contain a family history?

A

Yes in 20 percent of cases

18
Q

What are the risk factors of breast cancer?

A

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

19
Q

What are the common genes responsible for breast cancer?

A

BRCA1
BRCA2
TP53
PTEN
Undiscovered genes

20
Q

What is the function of BRCA1?

A

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

(PROTEIN THAT ACTS AS A TUMOUR SUPPRESSOR)

21
Q

What is the function of BRCA2?

A

DNA repair by HR (homologous recombination)

22
Q

What are the BRCA1 associated cancers?

A

Breast cancers, second primary breast cancer

Ovarian cancer

23
Q

What are the BRCA2 associated cancers?

A

Breast cancer, ovarian cancer, male breast cancer

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

24
Q

What are risk factors for colorectal cancers?

A

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

25
Q

What is the sequence of events for Adenoma to carcinoma?

A

Epithelium becomes hyperactive, adenoma forms, carcinoma forms

26
Q

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

A

few to no adenomas

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

27
Q

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

A

(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

28
Q

What are the clinical features of HNPCC

A

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

29
Q

What are clinical features of FAP?

A

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

30
Q

Describe the effect of attenuated FAP

A

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

31
Q

What condition is similar to attenuated FAP?

A

Recessive MYH polyposis

Common mutations in mut- MYH gene

32
Q

What can Multiple modifier genes explain?

A

May explain families with history of cancer and no identified mutation

May explain differences in cancer penetrance in families with same mutation

33
Q

How can you manage caner risk in Adenomatous Polyposis syndromes?

A

Surveillance
Surgery
Chemoprevention

34
Q

What portion of cancers are due to inherited mutations?

A

Only a small portion