Bowel cancer Flashcards
Who is offered bowel screening
> 55 years
One off scope screening test at 55
60-74 FIT tests 2 yearly
75 can request a kit
What provide for moderate risk families bowel cancer
Clinic appointment
Surveillance either one off at 55 or 5 yearly
NHS bowel screening
High risk families bowel cancer provided with
Appointmet genetic clinic
Genetic testing
Chemoprevention advice - aspirin
What prevention is considered in lynch syndrome
Colonosopies 2 yearly from age 25
Women hysterectomy and oophorectomy offered to women at risk of gynaecology cancers once have families
FAP prevention considered
Annual bowel checks from 10-13 years old
Sigmoidoscopy examine lower part of bowel
Colonoscopies examine more of bowel
What is lynch syndrome
Hereditary non polyposis colorectal cancer
What causes lynch syndrome
MMR genes - MLH1, MSH2, MSH6 and PMS2
What are MLH1 and MSH2 carriers offered screening ways
Rectal screening - colonoscopy every 2 years from 25-75 years
H pylori one off screening
NHS cervical screening
Hysterectomy + BSO after 35/childbearing
Epidemiology of increased cancer risk in lynch syndrome gene carriers
80% increased risk colorectal cancer in men
70% colorectal in women, 60% endometrial cancer
MSH6/PMS2 carriers screening
35-75 yeras colorectal screening annually
Hysterectomy alone after 45 years for PMS2
What are the amsterdam criteria used for
Diangostic criteria fro lynch sundrome
What is the criteria in amsterdam criteria
CRC <50 yeras
CRC <60 years + abnormality on IHC already detected
CRC at any age and one other lynch tumour at any age
CRC <60 and one 1st degree relative with lynch tumour <60
CRC <75 + >2 1st/2nd degree relatives w lynch tumours <75 - two cases must be FDR
What falls under lynch tumours
Colorectal cancer
Endometrail
Ovarian
Small bowel
Ureter
Gastric
Pancreatic
Hepatobiliary tract
Glioblastoma
Benign skin tumours/cacners
How is lynch syndrome testing done
MSI - microsatellite instability
IHC - immunohistochemical test
BRAF test
On tujmour tissue sample or a sample of family members in whom lynch syndrome most likely
Results of lynch syndrome testing
MSI high - dysfunctional MMR - needs further testing
Abnormal IHC - absence of MMR proteins and need for further genetic testing
+BRAF mutation = sporadic origin
What results mean can progress to further testing tfor lynch syndrome
MSI high, abnormal IHC and negative BRAF OR
Amsterdam +-> germline MMR testing
Who is offered predictive testing for inhertied cancer
Pathogenic variant identified in famuily
When is testing in children for cancer genes considered
TP53/FAP - earlier surveillance possible
When start surveilling indiviudals with mutation increasing cancer risk
25-30
What protects genetic testing for cancer insurance wise
Code on genetic testing and insurance
Not require or pressure into predictive or genetic tetsing
Dont ask for aor take into account resut of predictive genetic test if applying for insrance
Stop discrimination
What is the exception for insurance and predictive testing
Positive predictive Huntingtons disease and life insrance >500,000
Breast cancer risk factors
AMILY HISTORY
smoking
Obesity
Alcohol
Lack of exercise
Nulliparity or first pregnancy >30
Early menarche <12 and/or late menopause
Current or prev HRT use
Prev radiotherapy
Prev breast cancer
Prolonged breast feeding is protective
Types of risk stratification for breast cancer
By phenotype - eg age, number of relatives, breast and ovarian cancer
Genotype - herditary, family cluster, sporadic disease
What is herditary breast cancer
Single gene, high penetrance
BRCA1, BRCA2, TP53, PTEN, STK11, PALB2
What is a family cluster of breast cancer
Relatively common >1 gene
Low penetrance
Polygenic risk scores
Current options for genetic testing in breast cancer
Single mutation predicitve test - if known mutation in family
Standard panel test - BRCA1/BRCA2/PALB2 if FH breast/ovarian cancer meeting testing criteria 10% chance of finding a mutation
What % of colorectal tumours are caused by lynch syndrome
1 in 30
Over 1,100 colorectal cancers in UK per year
What causes lynch syndrome
LH1, MSH2, MSH6, PMS2 mutation - mismatch repair genes
What are core lynch cancers and other cancers it causes
Bowel
Endometrial
Other GI, gynaecological, CNS tumours, uroloigcal tumours
What is 3,2,1 in lynch syndrome
Amsterdam criteria - 3 lynch tunours, 2 successive generations, 1 diangosis <50
What should be done in all colorectal cancers NICE recommend
Lynch syndrome testing
How test for lynch syndrome
Immunohistochemistry, Microsatellite instability
If abnormal -> look for sporaduc non lynch cause of tumour - IF NON then evidence of lynch in blood DNA
Further testing for lynch syndrome
BRAF V600E + MLH1 promotor hypermethylation = common lynch misnomers - non lynch cause- if positive not lynch sydnroem
Germline gene testing
Mlh1, msh2,msh6, pms2
What is classical/attenutated FAP
Classical - highly penetrant - 1000s adenomas 100% malignancy risk
Attenuated - nont so highly penetrant - 10-100 adenomas, colonoscopy every 1 -2 years
Extracolonic FAP features
Gastric fundus polyps, duodenal polyposis, CHRPE (retinal hyperpigemnt), desmoid tumours, osteomas ,
What causes FAP
Inherited APC tumour supressor gene mutations
Rare single gene bowel cnacer conditions
MUTYH - recessive in aFAP - lifelong colonoscopy follow
DOMINANT
Peutz-Jeghers syndrome - STK11 (perioral hyperpigmentation, GI polyposis, other malignancy risk)
Juvenile polyposis - SMAD4 gene - GI polypisis, HHT
How treat FAP
Prophylactic colectomy offered form 20 years onwards
Lynch management bowel cancer
2 yearly colonsocopy 25-75 years
Gastric cancer risk lynch syndrome management
H.pylori testing, eradication
egular endoscopy screening not routinely offered
Fynaecological test lynch syndrome
Screening not effective
Risl reduconig
TAH/BSO once chilbearing complete
What medication can be used in lynch syndrme
Regular aspirin for at least 2 years esp colorectal cancers
