11. Cancer Genetics Flashcards
cancer
a disorder of cell growth
caused by alterations in genes which control cell growth
germline mutations
present in sperm or egg
are heritable
cause cancer family syndromes
somatic mutations
occur in non germline tissues
are nonheritable
who is at risk to hereditary cancer
hereditary cancers account for only a small proportion of all cancer
the cancer family history is the key to:
accurate risk assessment
effective genetic counselling
appropriate medical follow-up
when to suspect hereditary cancer syndrome
- cancer in 2 or more close relatives
- early age diagnosis
- multiple primary tumours
- bilateral or multiple rare cancers
incomplete penetrance
when you have the gene alteration but never show it (symptoms)
what are the two ways of classifying hereditary cancer
by tumour type
by type of gene mutated
what are the two main groups of tumour types
rare hereditary cancer syndromes
subset of common cancers which is hereditary, eg. colon cancer, breast cancer, ovarian cancer
what are the three type of genes that can be mutated
tumour suppressor genes
oncogenes
DNA damage-response genes
explain tumour suppressor genes
they slow down cell growth (like breaks)
cancer arises when both breaks fail
Retinoblastoma
tumour that develops in the pigment cells in the back of a childs eye
- occurs in heritable and nonheritable forms
- autosomal dominant transmission
non heritable retinoblastoma
- unilateral tumour
- no family history
- avg age of diagnosis is 2+
heritable retinoblastoma
- bilateral tumour
- 20% of cases have family history
- avg age of diagnosis is less than 1
familial adenomatous polyposis
- autosomal disorder, fully penetrant
- development of multiple initally benign colonic polyps and if untreated will progress into colon cancer
what is the treatment of familial adenomatous polyposis
to remove the colon
oncogene
accelerate cell division
normal genes regulate cell growth but when there is one mutation it leads to accelerated cell division
multiple endocrine neoplasia type 2 (MEN2)
inherited disorder of oncogene
what are three specific subtypes of the condition
thyroid C cell tumors,
parathyroid adenomas,
adrenal medulla tumors
common clinical disorder of DNA repair genes
common subset of colon cancer
HNPCC is due to defects in DNA mismatch repair
clinical features of HNPCC
early but variable age at CRC (colorectal cancer) diagnosis
tumour site in proximal colon predominates (majority of the cancer is in the upper part of the colon)
MSI - microsatellite instability
due to mismatch repair failure
what are the benefits of predictive genetic testing
- identifies those who are not at risk
- saves on screening resources
what is the intervention and recommendation for colorectal cancer
colonoscopy
begin at age 20-25 and repeat every 1-2 years
what is the intervention and recommendation for endometrial cancer
transvaginal ultrasound or endometrial aspirate
annually, starting at age 25-35
how much breast cancer is hereditary
5-10%
how much ovarian cancer is hereditary
15-20~%
what are some features that indicate increased likelihood of having BRCA mutations
- multiple cases of early onset breast cancer
- ovarian caner
- breast and ovarian cancer in the same woman
- bilateral breast cancer
- ashkenazi jewish heritage
- male breast cancer
BRCA 1
tumour suppressor gene on chromosome 17
autosomal dominant transmission
what is the lifetime risk of the cancers associated with BRCA1
breast cancer 50-85%
second primary breast cancer 40-60%
ovarian cancer 15-45%
what is the lifetime risk of the cancers associated with BRCA2
breast cancer 50-85%
male breast cancer 6%
ovarian cancer 10-20%
what are the benefits of BRCA testing
- identifies high risk individuals
- identifies noncarriers in families with a known mutation
- allows early detection and prevention strategies
- may relieve anxiety
- may allow targeted chemo
risk and limitations of BRCA testing
- does not detect all mutations
- continued risk of sporadic cancer
- efficacy of interventions unproven
- may rest is psychosocial or economic harm
surveillance options for breast cancer in healthy BRCA mutation carriers
monthly breast self exams (begin age 18)
and
early clinical surveillance (begin age 25)
