Download Clinical Genetics - Devon Sessional GPs

Clinical Genetics
Dr Carole Brewer, Consultant Geneticist
General Cancer Rules:
Any first degree relative affected doubles index patient risk, however
Some cancers have stronger genetic influence e.g. 1st degree relative with Thyroid cancer gives you
an 8-fold increased risk.
Some cancers have more environmental influence e.g. only 1.4 fold increased risk of relative has
Bladder cancer. Smoker s automatically double their risk of pancreatic cancer.
Ovarian Cancer
Population risk 1/48
No evidence-based screening- USS not very helpful as some ovarian cancers disseminate early.
“Empiric risk”:
Number of Relatives Affected
1
1
2
2
Age affected
< 50yr
50-60yr
< 60
>60
Risk
1/15
1/25- 1/25
1/5
1/10
Colo-rectal Cancers
Population risks: Males 1/18
Females 1/20
“Amsterdam criteria” can be used to risk categorise families – take into account numbers of
relatives affected, number of generations and age of onset. E.g. 3 relatives have colorectal cancer, 2
generations and one relative diagnosed at < 50yrs very likely to have inherited cancer such as Lynch
syndrome (previously known as hereditary non-polyposis colorectal cancer- HNPCC).
BSG guidelines are then used to indicate interval of colonoscopy screening:
High risk
High moderate risk
Low moderate risk
2 yearly
5yearly 50-75yr
1x only at 55yr
Lynch syndrome associated with more right sided colon cancers, with rapidly progressive adenoma
to adenocarcinoma and uterine carcinoma. All 1st degree relative need 18-24 monthly colonoscopy
from 25ys age. Tumour tissue immunochemistry and samples can be kept for future reference- 90%
are inherited and 10% sporadic. 4 genetic mutations have been identified: MLH1, MSH2, MSH6, and
PMS2. Blood genetic testing is very expensive £600 per gene. If gene mutation is detected,
predictive testing may be possible for relatives and if negative for the mutation they can be
relegated to the normal population risk (1/18) and no need for 2 yearly colonoscopy. Study 2011 by
John Burn (CAPP2 study) showed high dose aspirin, 600mg over 2 years reduced risk of colon cancer
by 60%.
So refer 1) For risk assessment where there is a complex FH 2) Genetic testing – ideally if affected
relative available for tissue sample.
Breast cancer
BRCA2 associated with moderate increased risk of prostate, pancreas and stomach. DNA from
affected case can be used for genetic testing in future.
For patients concerned about breast cancer , the Manchester scoring system recommended by NICE
to risk score patient for BRCA1/ 2 testing . Takes in to account number of relative affected from he
same lineage, age at incidence, history ovarian, pancreatic cancer, histology of cancer. Testing
recommended if > 20%risk.
Prostate Cancer
No specific gene but “familial aggregation”. Lots of “small genes” involved
FH doubles risk. Consider PSA testing is relative affected at <60y
Procedures after referral to Genetics Clinic
TRIAGE
CANCER MANAGEMENT SYSTEM : includes 1) Consent to access records
patient 3) Contact Cancer registry 4) Review histology
READY TO REVIEW PATIENT
NURSE COUNSELLOR
CONSULTANT CLINIC
2 ) Letter to