Loading presentation...

Present Remotely

Send the link below via email or IM


Present to your audience

Start remote presentation

  • Invited audience members will follow you as you navigate and present
  • People invited to a presentation do not need a Prezi account
  • This link expires 10 minutes after you close the presentation
  • A maximum of 30 users can follow your presentation
  • Learn more about this feature in our knowledge base article

Do you really want to delete this prezi?

Neither you, nor the coeditors you shared it with will be able to recover it again.


An Introduction to Genetics and Inherited Colorectal Disease

No description

Vicky Cuthill

on 30 January 2014

Comments (0)

Please log in to add your comment.

Report abuse

Transcript of An Introduction to Genetics and Inherited Colorectal Disease

An Introduction to Genetics and Inherited Colorectal Disease
People cannot be saved from getting cancer unless they know they are at risk
Always ask about family history
Accurate endoscopic assessment and careful pathological polyp assessment vital
If in doubt - get advice
Genetics overview
Gene mutations
Inheritance patterns
Inherited pre-malignant conditions affecting the GI tract
Family history - who is at risk?

Vicky Cuthill Nurse Practitioner - The Polyposis Registry St. Mark's Hospital
Human cells contain 46 chromosomes - 2 types
sex chromosomes - determine gender
autosomal chromosomes
come in 22 pairs plus 1 pair of sex chromosomes
DNA is made up of four nitrogen-rich bases:-
Adenine (A), Thymine (G), Guanine (T),
Cytosine (C)
Together these form the genetic alphabet, comprised of just 4 letters A, G, T and C
Genetics Overview


Familial Adenomatous Polyposis (FAP)
Peutz Jeghers Syndrome (PJS)
Juvenile Polyposis Syndrome (JPS)
Serrated Polyposis Syndrome (SPS)
Lynch Syndrome/Hereditary Non Polyposis Colorectal Cancer (HNPCC)
Cowden's Syndrome
Conditions affecting the GI Tract
Dominant inheritance

Familial Adenomatous Polyposis (FAP)

FAP - other considerations

Upper GI disease including adenomas/carcinomas of:
duodenum, ampulla, gall bladder and bile duct, pancreas
Extra-colonic manifestations and other cancers e.g thyroid
Desmoid disease

STK11 (LKB1) gene on Chromosome 19
characterised by pigmented patches on lips, fingers and toes

Peutz Jeghers Syndrome

PJS polyps can develop throughout the gastrointestinal tract
Early onset – severe abdominal pain, intussuception
Increased cancer risk
Management involves endoscopic surveillance, management of polyps and regular clinic assessment to prevent other cancers developing (e.g. breast, testicular, ovarian, pancreatic)
Peutz Jeghers syndrome

SMAD 4 gene Ch. 18
BMPR1 Ch 10
ENG 1 Ch 9
Characterised by Juvenile polyps
Polyps auto-rotate, bleed and often fall off
Endoscopic management, surgery sometimes required
Stomach, duodenual and colorectal polyps

Juvenile Polyposis Syndrome (JPS)

Lynch Syndrome (LS) is when there is a known mismatch repair defect
Familial colorectal cancer type x is when the Amsterdam criteria is fulfilled but no gene mutation is found
Detailed family history vital
At risk families considered using the Amsterdam and/or Bethseda criteria
Think of 3, 2, 1
3 or more relatives with LS related cancer
2 generations (or more)
1 cancer under age 50
Lynch Syndrome
MAP - a recessively inherited

MYH associated polyposis (MAP)
MYH gene chromosome 1
Phenotype similar to FAP
Fewer colorectal adenomas - hundreds rather than thousands
? Fewer duodenal adenomas
Natural history still being mapped

Genetic Testing
A predictive genetic test can only be offered if the causative mutation is known
DNA must, therefore, be available from an affected member of a family to do a mutation search
Before predictive testing, at risk relatives must have genetic counselling and give written consent
The result should be given by someone who understands the implications of both a positive and negative result
Children should not be tested unless the result would affect their medical care
Once the mutation is known, prenatal testing + pre-implantation genetic diagnosis may be available

Information about as many relatives as possible
gradually extending the family tree
Names including maiden names and all name changes
Dates of birth and death where applicable
Place of residence / hospitalisation
Illnesses and dates of surgery if known

What information is needed
when taking a family history?

Who to test?
Died CRC
A/W at 80
50 yrs
Gen diagnosis
of FAP age 48
46 yrs
40 yrs
Useful reading
www.genetics.edu.au - excellent website with lots of fact sheets
Gastrointestinal nursing journal - inherited colorectal cancer series about to be published!
You tube - excellent short clips on genetics etc.
>100 colorectal adenomas
Ch. 5
1% of colorectal cancers
Average age of colorectal cancer is 39
100% lifetime risk of colorectal cancer without preventative surgery
Colonoscopic surveillance initially
Colectomy with IRA
RPC with pouch formation (2 stage with temporary covering ileostomy)
Regular surveillance of rectum/pouch
Upper GI surveillance from age 25
Serrated Polyposis Syndrome (SPS)
Serrated polyps develop in the colon
genetic basis yet to be discovered
Follows a dominant inheritance pattern
Endoscopic management (annual colonoscopies)
Increased risk of colorectal cancer if polyps not removed - surgery required if polyps not manageable endoscopically
Chromosomes are made up of DNA
In the lab, chromosomes are stained to produce distinctive banding patterns
Genes are segments of DNA
that issue chemically
coded 'messages' to make
Each 'word'
is a combination of 3
of the 4 chemical
The sequence of 3 letter words (codons)
produces a recipe for amino acids
that combine to form proteins
Genetic Mutations
We all have variations in the genetic code - it's why we're unique
Most variations are harmless
However, some can make the gene faulty (mutations) so a particular protein is not produced properly, produced in wrong amounts or not at all.
When the faulty genes are contained in the egg or sperm cells they can be passed on - inherited (germline)
De novo
mutation = first in the family
Somatic mutations occur at cellular level e.g. single polyps/sporadic cancer
Died CRC
The Polyposis Registry and Family Cancer Clinic - Level v, St. Mark's Hospital, Harrow

020 8235 4270 (Polyposis)
020 8235 4266 (Family cancer)

Lynch Syndrome
Genes responsible:
MLH1, MSH2, MSH6, PMS2 and EpCAM
Mutations in any of these genes prevent the proper repair of DNA replication mistakes.
Genetic testing usually starts with tumour tissue from people diagnosed with colorectal cancer or LS associated cancer (endometrial, ovarian, stomach, small bowel, bile duct/gall bladder, brain, pancreas, urothelial, skin)
If abnormal IHC is found or the tumour tests positive
for MSI, the next step is to look for a specific
mutation using DNA extracted from a blood sample
Gene mutations and inheritance Patterns
Types of mutations
Dominantly inherited GI conditions
Dominantly inherited GI conditions
MAP, genetic testing and family history taking
Affected female
Affected male
Unaffected female
Unaffected male
Full transcript