GENETICS Flashcards
what percentage of breast and ovarian cancer is hereditary?
5-10%
what percentage of breast cancer is due to family clusters?
15-20%
list the causes of dereditary susceptibility to colorectal cancer…
FAP (1%), sporadic (65-85%), familial (10-30%), HNPCC (5%)
key factors of germline mutations
inherited from a single alteration in egg or sperm, heritable, cause cancer family syndromes
what is looked for in leukaemia genetics
translocation and bra-abl (oncogene) fusion
Retinoblastoma caused by…
rb1 gene 2 copies
colon cancer - mutlistep carcinogenesis process overtime
loss of apc > activaiton of kras > loss of 18q > loss of tp53 > other alterations
details of lynch syndrome/ HNPCC
mutaiton mismatch repair genes, excess of colorectal endometrial, urinary tract, ovarian and gastric cancers, carcinoma sequence for polyp formation
what are the features of HNPCC
tumor site in the proximal colon, asprin often used for prevention
cancer frisks in lynch syndrome
endometrial, colon, stomach, ovarian, biliary tract, urinary tract
BRCA1 and 2 associated cancers…
breeast (60-80%), ovarian (20-50%), males have an increased ricks of prostate cancer and breast cancer especially with the BRCA2 gene
draw an autosomal dominant inheritance mendelian flowchart (pedigree chart)
theres no skipped generations, each child has a 50% chance of inheriting the mutation, it Is equally transmitted by men and women (dominant, high penetrance syndrome)
when to suspect a hereditary cancer syndrome
cancer in 2< close relatives on the same side of the family,
early age diagnosis,
multiple primary tumours,
bilateral of multiple rare cancers,
evidence of autosomal dominant transmission
what is the process of genetic consulatation?
fhx, confirm cancer, risk estimation , counselling, give interventions
what is the age women are screened at
xray mammography at 50yo
what can be done to reduce the risk of breast cancer
prophylactic mastectomy, oophorectomy
surveilance for crc
use a colonoscopy, give prophylactic asprin if a gene carrier
Genetic testing for Lynch Syndrome
IHC for mismatch repair gene proteins or microsatellite instability testing (MSI)
Benefits, Risks, and Limitations of Genetic Testing
Identifies highest risk, Identifies non-carriers in families with a known mutation, Allows early detection and prevention strategies, May relieve anxiety. Does not detect all mutations, Continued risk of sporadic cancer, Efficacy of interventions variable, May result in psychosocial or economic harm.
what is Li-fraumini syndrome
germline mutation TP53
is the breast cancer gene dominant or recessive?
mutations in the BRCA1 and BRCA2 genes are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person’s chance of developing cancer.
neurofibromatosis type 1 (NF1)
autosomal dominant, prevelance 1/2500-3500
how can you disagnose NF (sx’s)
2 or more of: café du lait spots, neurofibromas, axillary freckling, lisch nodules (specks in the iris), optic glioma, thinning of the long bone cortex, fhx.
further sx’s
macrocephaly, short stature, dysmorphic features (noonan look), learning difficulties, epilepsy, scoliosis, pseudoarthritis of the tibia, raised bp due to renal artery stenosis or phaeochromocytoma, neoplasia (cns optic gliomas, or endocrine)
genetics of nf1
autosomal dominant, 17q gene (tumour supressor gene), 50% due to new mutaitons (usually parental in origin (from the dad))
what are the main features of nf2?
acoustic neuromas (bilateral), cns and spinal tumours, few CAL spots. The nf2 gene is on chromosome 22
Tuberous sclerosis (TS)
incidence 1/7000 newborns, autosomal dominant.
what is the triad of TS
epilepsy, learning difficulties, skin lesions (austistic features, infantile spasms and myoclonic seizures)
what are the genetics of ts?
autosomal dominant, variable expression, 3 genes both on different chromosomes both cause ts - TSC1 and TSC2
other features of ts
skin lesions (depigmented macules, angiofibromas, fibrous plaque forehead, shagreen patches, ungual fibromas). Kidney cysts and angiomyolipomata, phakomas in the eye (benign unless on the macula), rhabdomyomas in the heart.
how can you screen for ts?
skin signs, retinal examination, crainal MR scan, retinal ultrasound, echo.
myotonic dystrophy clincial features
bilateral late-onset cataract, muscle weakness (effects distal muscles, facial muscle and the diaphragm the most), stiffness, myotonia, low motivation, bowel problems, DM, heart block, death post-anaesthetic risk if not monitored, congenital myotonic dystrophy.
genetic features of myotonic dystrophy
autosomal dominant, caused by a CTG repeat, this repeat gets more severe with each generation.
Amyotrophic lateral sclerosis…
sporadic, 10%familial, Progressive muscle weakness, wasting and increased reflexes (ie upper and lower neurone signs), Limb and bulbar muscles involved. Caused by superoxide dismutase (SOD)
What are the clinical features of huntingtons disease
movement disorder - chorea, athetosis, myoclonus, rigidity. Cognitive changes - poor planning & memory - subcortical dementia (executive function), NOT classical dementia, Personality change - Irritable, Apathetic, loss of empathy, ‘A different person’, disinhibition, self centred, Psychiatric disease - depression, paranoia, psychosis. CAG expansion, adult onset, Autosomal Dominant
