Transcript Part Two - West Lakes GP Training

Part Two
Welcome back
Familial Cancer Genetics
Cancer Genetics
• 5-10% of all cancer clearly linked to an inherited gene
alteration
• If cancer seen at younger ages (before 50) possible that
inherited genes increased susceptibility
• Some genetic conditions increase someone’s risk of getting
several different types of cancer at young age (eg. LiFraumeni syndrome, MEN 1)
• Some gene alterations lead to uncontrolled cell growth:
– tumour suppressor genes
– oncogenes
– DNA repair genes
Breast Cancer
• BRCA 1 & BRCA 2 testing may be available for people at
high risk, but others genes known to be involved
• If gene alteration found, woman at up to 80% lifetime risk
of developing breast cancer
• Carry risk of other cancers; ovary (BRCA 1 = 44%, BRCA 2 =
27%), and a slightly increased risk prostate, pancreas and
some other cancers
• Dominantly inherited through families (ie. only one copy
of the altered gene needed for it to have effect)
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
At conception
Unaffected
Affected
Hereditary
gene alteration
Somatic
mutation
Cancer
1 Somatic
mutation
Normal Tissue
Hereditary
gene alteration
Somatic
mutation
Cancer
2 Somatic
mutations
Cancer
What would indicate that a woman is at
higher risk of developing breast/ovarian
cancer?
Relative with breast cancer
before the age of 40
Relative with
male breast
cancer
2+ relatives with
ovarian cancer
Relative with
bilateral breast
cancer
2+ relatives on the same
side of the family affected
by breast cancer (especially
if affected at younger ages)
Breast Cancer Referral
Number of Relatives
Age at diagnosis
Refer to Genetics
1 (first degree)
> 40 years
No
1 (first degree)
< 40 years
Yes
1 (first degree) bilateral
Primary <50 years
Yes
1 Male (first degree)
Any age
Yes
≥ 2 (one first degree)
average <60 years
Yes
FH with Jewish ancestry
Yes
Strong FH on paternal side
Yes
Tumour associations - ovary,
endometrium, prostate, bowel
Yes
Low risk – manage in primary care
Case 1
• Older age of onset
• Different sides of the family
Breast cancer
65
70
46
Kay
76
49
51
53
55
Reassure and explain population risk. Advise on symptom awareness and to report any
changes in family history
Ovarian Cancer
Number of Relatives
Age at diagnosis
Refer to Genetics
1 fdr no other FH of cancer
Any age
No
2 fdr
Any age
Yes
1fdr and 1sdr
Any age
Yes
1fdr or sdr with ovarian and
1 fdr or sdr with breast or
colorectal cancer (at least 1 fdr)
Any age
Yes
Refer – high risk
• Young age onset
Case 2
• Equal transmission
through men
• Multiple tumours in
one individual
• Breast and ovarian
cancer
42
48 breast cancer
56 ovarian cancer
Breast cancer
32
Ovarian cancer
Janet
Colorectal Cancer
Familial Adenomatous Polyposis (FAP)
Hereditary Non-Polyposis Colorectal Cancer
(HNPCC).
Other cancers associated with
HNPCC – endometrial, stomach,
ovarian
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Bowel Cancer
Number of relatives
Age at diagnosis
Refer to Genetics
1 fdr
>50 years
No
1 fdr
< 50 years
Yes
2 fdr (includes both parents)
Any age
Yes
1fdr and 1 sdr
Any age
Yes
3+ relatives
Any age
Yes
FH of known hereditary colorectal
cancer syndrome
(e.g. HNPCC, FAP)
Any age
Yes
HNPCC related cancers include endometrial, gastric,
ovarian, pancreatic and urothelial
Case 3
73
35
died in war
60’s
73
Colorectal cancer
75
43
77
32
Peter
Refer – moderate risk
Young age of onset (under 45)
68
78
Case 4
Colorectal
cancer
Endometrial
cancer
55
69
49
42
80
75
48
George
Refer – High risk
Young age of onset,
Endometrial and Bowel
Two generations, Polyps
30
Martin
39
Polyps
42
78
Referral for family history of cancer
• Young age at onset,
• Pattern of similar tumours on one side of the
family (or multiple primaries in one individual)
• Use national/local guidelines e.g. NICE familial
breast cancer
• Remember ethnicity e.g. – Chinese, Indian,
Ashkenazi Jewish ancestry
• If in doubt - Contact the Clinical Genetic Service
Patient Information
• Detailed information of affected family
members required
• Patient will receive information regarding level
of risk and options
• Will not necessarily mean a genetic test
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
At conception
Unaffected
Affected
Familial Hypercholesterolaemia
• If fulfil Simon Broome criteria, refer to
specialist lipidologist
• Where Genetic testing is not available,
cascade testing for family members by
fasting lipid profile
• Children tested below 10 years
• Boys have lower cholesterol during puberty
Heart UK Definition using
Simon Broome Register
Definite Familial Hypercholesterolaemia:
Total Cholesterol
LDL Cholesterol
Adult
>7.5mmol/l
>4.9mmol/l
Child < 16
>6.7mmol/l
>4.0mmol/l
PLUS
b) Tendon xanthomas in patient, or in 1st degree
relative (parent, sibling, child), or in 2nd degree
relative (grandparent, uncle, aunt)
OR
c) DNA-based evidence of an LDL receptor
mutation or familial defective apo B-100
Heart UK Definition using
Simon Broome Register
Possible Familial Hypercholesterolaemia:
Total Cholesterol
LDL Cholesterol
Adult
>7.5mmol/l
>4.9mmol/l
Child < 16
>6.7mmol/l
>4.0mmol/l
PLUS
• d) Family history of myocardial infarction: below age of 50
in 2nd degree relative or below age 60 in 1st degree
relative
Or
• e) Family history of raised cholesterols:
– >7.5 mmol/l in adult 1st or 2nd degree relative or
– > 6.7 mmol/l in child or sibling under 16
X-LINKED INHERITANCE WHERE THE MOTHER IS A CARRIER
Father
Parents
Mother
(Unaffected)
(Carrier)
Gametes
X
Y
X
X
At conception
Daughter
Daughter
(Carrier)
Son
Son
(Affected)