SlideShare a Scribd company logo
Cancer Genetics
SHOULD WE ALL GET OUR GENES PROFILED?
ASPEC / March 15, 2021 / Robert Miller MD
“the fault…is not in our stars but in ourselves”
To keep it simple
- Are the cancer genes inherited and run in families
(germ line and found in every cell in the body) or acquired during life
(somatic mutation, and only present in the malignant cells)?
- How can you tell them apart and which is more common?
- What is the role of a genetic counselor in making sense of a
worrisome family history and what tests would they recommend?
Francis Crick in
1958
Is Cancer a Genetic Disease?
Since the identification of Oncogenes that could turn normal cell into cancer
cells, it’s been assumed that finding and fixing the gene should solve this
problem…but
It’s more complicated
May be more than one gene associated with the cancer
May be that conventional genes (protein coding genes) are only part (a small
part) of the problem (epigenetics trumps genetics or microbiome genome)
May be that cancer is not a genetic problem but a metabolic problem
Complexity of Genetics
Human Genome Project has also led to a change in our understanding of human traits and how we teach
them - one example is eye color. For many years, students were taught that one dominant gene controlled
brown or blue eyes In fact, at least ten genes each of which comes in several "flavors," contribute to
eye color
Other traits are even more complicated; for example, around 80 percent of a person's height is controlled
by more than 700 genomic variants, each one having a very small influence.
www.genome.gov
The human genome contains approximately 3 billion of
these base pairs, which reside in the 23 pairs of
chromosomes within the nucleus of all our cells. Each
chromosome contains hundreds to thousands of genes,
which carry the instructions for making proteins. Each of
the estimated 30,000 genes in the human genome makes
an average of three proteins.
Protein coding genes make up only 1.5% of the genome
Humans may have far fewer genes than assumed - somewhere between 20,000 to
25,000.
That number sounds embarrassingly small considering that nematode worms have
about 20,000 too, grapes have about 30,000 and tomatoes have nearly 32,000.
Who has more
genes, us or a
tomato?
It’s not this simple!
Protein coding genes are a very small part of the picture
Tumor Evolution in the Transcriptome, Epigenome, and
Epitranscriptome
https://youtu.be/UQecetRMzWI
As cancer is evolving there are more changes going on in the epigenetic
modifications (methylation) than in the genes themselves
All cancers are epigenetically abnormal
Maybe cancer is
not genetic but
metabolic and
we should be
looking at the
mitochondria not
the nucleus.
Prof. Thomas Seyfried
Types of genes linked to cancer
Tumor suppressor genes. These are protective genes. Normally, they limit cell
growth by:
•Monitoring how quickly cells divide into new cells
•Repairing mismatched DNA
•Controlling when a cell dies
Examples of tumor suppressor genes include BRCA1, BRCA2, (inherited for breast cancer)
and p53 or TP53 (most commonly mutated gene in people with cancer and acquired)
Oncogenes. These turn a healthy cell into a cancerous cell. Mutations in these genes are not known to be
inherited.
Two common oncogenes are:
•HER2
•The RAS family of genes
DNA repair genes. These fix mistakes made when DNA is copied. Many of them function as tumor
suppressor genes. BRCA1, BRCA2, and p53 are all DNA repair genes and may be inherited or acquired
Two Questions about Genetics
and cancer
1. Did you inherit this (hereditary or germ line). From a
blood test or saliva. Tell you what other cancers to
expect and the need to have family testing.
2. Did the mutation occur after birth (acquired or somatic),
Find this from a genetic analysis of the cancer tissue
(biopsy or liquid biopsy) may predict how malignant and
what treatment drug options will be effective.
For prostate cancer it may be worth testing for inherited mutations (to help
predict the course of the disease and for family counseling) and cell molecular
genetics (to predict how malignant or aggressive the cancer is, does the
patient even need to be treated?)
For lung cancer it’s necessary to test for acquired mutations because it will
predict which drugs or immunotherapy approached may be useful.
Breast Cancer need both for familial or inherited testing (effects management as
well as family counseling) and somatic testing (impacts on specific treatment
decisions)
Paradox that triple
negative do better
with chemoRx if they
are BRCA + , also
BRCA do better with
PARP inhibitors and
the more mutations
the more likely to
respond to
immunotherapy
Which is more common, inherited
(hereditary) or acquired or somewhere
in between?
- Sporadic
- Familial Cancer
- Hereditary Cancer
Sporadic
Most cancers – 75% to 80% – are
sporadic. In sporadic cancer, the gene mutations
that cause the cancer are acquired (occur only in
the tumor cells, somatic) and are not inherited
Genetic analysis of
the cancer tissue to
find somatic or
acquired genetic
mutations.
EGFR mutation
found in lung
cancer will guided
the physician the
three drugs
currently approved
and effective for
cancers with this
type of mutation.
Familial Cancer
Certain common cancers, such as breast, prostate and
colon cancers, may occur in more than one member of the same
family, thought to be the result of multiple influences.
A combination of several genes and other factors, such as diet and
exercise, all contribute a small amount to an increased risk of
developing cancer. Such families may have a moderately increased
risk to develop cancer.
Hereditary Cancer Only 5% to 10% of all cancers are
hereditary and due to a gene mutation that is present from birth.
Usually, the mutation was passed from a mother or father to the
child. Because of this, there is usually a recognizable pattern of cancer on
one side of the family.
There are several clues which suggest that there is hereditary cancer in a family.
These can include:
- Age of diagnosis is usually younger than in sporadic forms of cancer (often
younger than age 50).
- Multiple family members have the same or related types of cancer.
- Cancer is more likely to develop in more than one site in the body.
- Rare cancers may occur, for example, male breast cancer.
February 4, 2021 N Engl J Med 2021; 384:440-451
Breast Cancer Risk Genes — Association Analysis in More than 113,000 Women
Breast Cancer Association Consortium
N Engl J Med 2021; 384:428-439
Among European women, approximately 6.8% of the patients and 2.0% of the controls had protein-truncating
variants in any of the 9 genes associated with breast cancer risk; in addition, 2.2% of the patients and 1.4% of
the controls had missense variants in CHEK2.
Estimated Absolute Risk of Breast Cancer
Associated with Protein-Truncating Variants in
8 Genes
We used a panel of 34
putative susceptibility
genes to perform
sequencing on samples
from 60,466 women with
breast cancer and
53,461 controls.
In the 90% of cancers that are sporadic it takes time to accumulate enough
mutations to get cancer
In the 10% of cancers that are hereditary every cell starts out with at least
one mutation so cancer is more likely and shows up more quickly
High-risk syndromic genes are
highlighted in green. The
moderate-penetrance genes
(highlighted in red) have an
approximate relative risk of 2.0.
The common, low-risk genes are
shown in orange.
Foulkes, N Engl J Med 2008;
359:2143-2153
Uncommon high risk mutations =
hereditary and more common
low risk gene mutations =
familial
A diagram showing the major cancer
genes for some cancers. The larger
the gene name, the more frequently
that gene is defective in that cancer
type.
Cancer Genes
•So far, 291 cancer genes have been
reported, more than 1% of all the
genes in the human genome.
•90% of cancer genes show somatic
mutations in cancer, 20% show
germline mutations and 10% show
both.
2004 Census of Known
Cancer Genes
Nat Rev Cancer. 2004 Mar; 4(3): 177–183.
http://atlasgeneticsoncology.org/Genes/Geneliste.html
Indexation date : Sun Feb 28 12:28:29 CET 2021
Cancer risk associated with
inherited BRCA1 mutations
Risks in women
•Breast cancer: The lifetime risk for a women with a BRCA1 mutation is about 65 percent compared to 12.5 percent for an
average risk woman.
•Ovarian cancer: The lifetime risk for a women with a BRCA1 mutation is about 40 percent compared with 1.3 percent for an
average risk woman.
•Second breast cancer in women who have already been diagnosed with breast cancer: The lifetime risk is about 40 percent.
•Uterine cancer: There is a slightly increased risk for a rare form of aggressive uterine cancer, the estimated risk to age 70 is less
than 5 percent
Risks in men
•Prostate cancer: The lifetime risk for a man with a BRCA1 mutation is about 16 percent compared to 12 percent for an average
risk man. Prostate cancers in men with inherited BRCA1 mutations may be more aggressive than in men without an inherited
mutation.
•Male breast cancer: The lifetime risk for a man with a BRCA1 mutation is about 2 percent.
Risks in both men and women
•Pancreatic cancer: The lifetime risk for a person with a BRCA1 mutation is about 5 percent compared to 1 percent for an average
risk person.
•Research on how mutations in the BRCA1 gene affect cancer risk is ongoing. Some research suggests that BRCA1 mutations
may increase risk for melanoma. However, because these studies are not conclusive, genetics experts often look at a person’s
family history of cancer to help people with BRCA1 mutations understand their risk for additional cancers.
In a moving New York Times op-ed,(March 24, 2015) Angelina Jolie Pitt revealed today that she had preventive
surgery last week to remove her ovaries and fallopian tubes. The news comes two years after she disclosed that
she had a preventive double mastectomy touching off a national conversation about women and cancer risk
Jolie Pitt carries a mutation in the BRCA1 gene that gives her an 87% chance of developing breast cancer and a
50% chance of developing ovarian cancer. She lost her mother, grandmother, and aunt to cancer.
Odds of having BRCA mutation
In the general population : (0.25%)
BRCA 1 ( 1 in 300) and BRCA 2 ( 1in 800)
Ashkenazi Jewish frequency of either is 1in 40 (2.5%)
Non-Ashkenazi Jewish ancestry
●Women with breast cancer (any age): 1 in 50 (2 percent)
●Women with breast cancer (younger than 40 years): <1 in 10 (<10 percent)
●Men with breast cancer (any age): 1 in 20 (5 percent)
●Women with ovarian cancer (any age): 1 in 8 to 1 in 10 (10 to 15 percent)
Ashkenazi Jewish ancestry
●Women with breast cancer (any age): 1 in 10 (10 percent)
●Women with breast cancer (younger than 40 years): approximately 1 in 3 (30 to 35
percent)
●Men with breast cancer (any age): 1 in 5 (19 percent)
●Women with ovarian cancer or primary peritoneal cancer (all ages): approximately 1 in 3
(36 to 41 percent)
Founder Population
Members of the Jewish community who trace their roots to Central or Eastern Europe are
known as Ashkenazi Jews.
Although today members of this community are found around the world, Ashkenazi Jews for
centuries were a geographically isolated population. The isolation experienced by this
population means its members can trace their ancestry back to a small number of members
known as “founders.”
The study in in the journal Nature Communications was funded by the National Institutes of Health and the National
Science Foundation, along with several private foundations.
Nat. Commun. 5:4835 doi: 10.1038/ncomms5835 (2014).
“Ashkenaz” in Hebrew refers to Germany, and Ashkenazi Jews are those who originated in Eastern Europe, no more than half
of their DNA comes from ancient Europeans. Those ancient people split off from the ancestors of today’s Middle Easterners
more than 20,000 years ago, with a founding group of about 3,500 to 3,900 people.
The rest of the Ashkenazi genome comes from the Middle East, this founding group “fused” with the European founding
group to create a population of 250 to 420 individuals. These people lived 25 to 32 generations ago, and their descendants
grew at a rate of 16% to 53% per generation, the researchers calculated.
Previous analyses of recent AJ history highlighted a narrow population bottleneck of only hundreds of individuals in late
medieval times, followed by rapid expansion.
Today there are more than 10 million Ashkenazi Jews around the world,
The AJ population is much larger and/or experienced a more severe bottleneck than other founder populations, such as
Amish, Hutterites or Icelanders, whose demographic histories facilitated a steady stream of
genetic discoveries.
Nat. Commun. 5:4835 doi: 10.1038/ncomms5835 (2014).
Final Recommendation Statement
BRCA-Related Cancer: Risk Assessment, Genetic
Counseling, and Genetic Testing
August 20, 2019
testing begin with a relative with known BRCA-related cancer or relative with the highest probability of mutation
should be tested. Because risk assessment is primarily based on family history, it is unclear how women with a
limited or unknown family history should be assessed
https://uspreventiveservicestaskforce.org/
What do you learn from seeing a genetic counselor?
Case study from Genetics Counselor at Mass
General
https://youtu.be/NRRws1OoT_g
Pedigree Chart to
map out the family
tree
Turns out she
has BRIP1
(ovarian
cancer gene)
and HOXB13
(prostate
cancer gene)
Then her uncle gets
tested and he has
both so he can
screen for prostate
cancer
Then her brother
gets tested and he
has prostate so he
can screen for
prostate cancer
Then her cousin
gets tested and he
is negative for both
I wouldn’t really recommend whole exome/genome sequencing for individuals with no medical indication to
do so. This does have to do with clinical utility and interpretation of data.
As for individuals who are adopted or would like more info about their health, I would recommend looking into
some proactive health panels. Options through Invitae are particularly informative and generally affordable.
There is even a genetic counseling process available to individuals who’d like to order this testing-
https://www.invitae.com/en - all the options
https://www.invitae.com/en/staying-healthy - Staying healthy (mainly cancer and cardio)
https://www.invitae.com/en/pregnancy- Reproductive/Carrier screening
23andMe is fun information…. Some of the carrier screening is done on their platforms however, they do not
do full gene sequencing, but rather targeted mutation analysis. Any findings on 23andMe need to be
confirmed by clinical and diagnostic lab.
Advice from Deena Whaba the Genetics Counselor at Saint Anthony's
https://www.genome.gov/event-calendar/Bold-Predictions-for-Human-Genomics-by-2030
#6 , Genomic Testing will become commonplace like a standard medical test
#8, A person’s complete genome will be available on their smart phone in a user friendly format
https://www.pancan.org/facing-pancreatic-cancer/about-
pancreatic-cancer/risk-factors/genetic-hereditary/
In some cancers like
pancreas cancer, the role
of family history and
genetics may be huge
So far (2020) have
only identified the
relevant gene
mutation in less
than 20% of the
cases
Pancreas Cancer
High risk genes
are rare, lower
risk genes are
more common
Huge individual variation of little
or unknown significance
Current Status of Pancreas Cancer Genes

More Related Content

What's hot

Cancer epigenetics
Cancer epigenetics Cancer epigenetics
Cancer and Oncogenesis
Cancer and OncogenesisCancer and Oncogenesis
Cancer and Oncogenesis
Sougata Ganguly
 
Cancer genetics and diagnosis
Cancer genetics and diagnosisCancer genetics and diagnosis
Cancer genetics and diagnosis
Rajpal Choudhary
 
Oncogenes
Oncogenes Oncogenes
Oncogenes
VISHAKHA UPADHYAY
 
An Overview of Cancer Genetics
An Overview of Cancer GeneticsAn Overview of Cancer Genetics
An Overview of Cancer Genetics
Dana-Farber Cancer Institute
 
Understanding BRCA1/2 Cancer Risk
Understanding BRCA1/2 Cancer RiskUnderstanding BRCA1/2 Cancer Risk
Understanding BRCA1/2 Cancer Risk
Dana-Farber Cancer Institute
 
biology of cancer
biology of cancerbiology of cancer
biology of cancer
PrashantSharma807
 
Cancer genome (2)
Cancer genome (2)Cancer genome (2)
Cancer genome (2)
Nilesh Kucha
 
Tumour suppressor genes
Tumour suppressor genes Tumour suppressor genes
Tumour suppressor genes
Dhanya K C
 
The Genetics of Cancer
The Genetics of CancerThe Genetics of Cancer
The Genetics of Cancer
mpattani
 
Cancer Genetics - Denise Sheer
Cancer Genetics - Denise SheerCancer Genetics - Denise Sheer
Cancer Genetics - Denise Sheer
Denise Sheer
 
Cancer biology
Cancer biologyCancer biology
Cancer biology
RAJENDRA SINGH
 
Oncogenesis
OncogenesisOncogenesis
Oncogenesis
MD Specialclass
 
Chapter 5 hereditary cancer syndrome next generation
Chapter 5 hereditary cancer syndrome next generationChapter 5 hereditary cancer syndrome next generation
Chapter 5 hereditary cancer syndrome next generation
Nilesh Kucha
 
P53
P53P53
Breast Cancer: A focus on BRCA Mutations.
Breast Cancer: A focus on BRCA Mutations.Breast Cancer: A focus on BRCA Mutations.
Breast Cancer: A focus on BRCA Mutations.
Mohamed Abdulla
 
Tumor suppressor genes
Tumor suppressor genesTumor suppressor genes
Tumor suppressor genes
fatmafars
 
Oncogenes
OncogenesOncogenes
Chapter 3 hallmarks of cancer
Chapter 3 hallmarks of cancerChapter 3 hallmarks of cancer
Chapter 3 hallmarks of cancer
Nilesh Kucha
 
Hereditary Cancer Syndrome
Hereditary Cancer SyndromeHereditary Cancer Syndrome
Hereditary Cancer Syndrome
Sujoy Dasgupta
 

What's hot (20)

Cancer epigenetics
Cancer epigenetics Cancer epigenetics
Cancer epigenetics
 
Cancer and Oncogenesis
Cancer and OncogenesisCancer and Oncogenesis
Cancer and Oncogenesis
 
Cancer genetics and diagnosis
Cancer genetics and diagnosisCancer genetics and diagnosis
Cancer genetics and diagnosis
 
Oncogenes
Oncogenes Oncogenes
Oncogenes
 
An Overview of Cancer Genetics
An Overview of Cancer GeneticsAn Overview of Cancer Genetics
An Overview of Cancer Genetics
 
Understanding BRCA1/2 Cancer Risk
Understanding BRCA1/2 Cancer RiskUnderstanding BRCA1/2 Cancer Risk
Understanding BRCA1/2 Cancer Risk
 
biology of cancer
biology of cancerbiology of cancer
biology of cancer
 
Cancer genome (2)
Cancer genome (2)Cancer genome (2)
Cancer genome (2)
 
Tumour suppressor genes
Tumour suppressor genes Tumour suppressor genes
Tumour suppressor genes
 
The Genetics of Cancer
The Genetics of CancerThe Genetics of Cancer
The Genetics of Cancer
 
Cancer Genetics - Denise Sheer
Cancer Genetics - Denise SheerCancer Genetics - Denise Sheer
Cancer Genetics - Denise Sheer
 
Cancer biology
Cancer biologyCancer biology
Cancer biology
 
Oncogenesis
OncogenesisOncogenesis
Oncogenesis
 
Chapter 5 hereditary cancer syndrome next generation
Chapter 5 hereditary cancer syndrome next generationChapter 5 hereditary cancer syndrome next generation
Chapter 5 hereditary cancer syndrome next generation
 
P53
P53P53
P53
 
Breast Cancer: A focus on BRCA Mutations.
Breast Cancer: A focus on BRCA Mutations.Breast Cancer: A focus on BRCA Mutations.
Breast Cancer: A focus on BRCA Mutations.
 
Tumor suppressor genes
Tumor suppressor genesTumor suppressor genes
Tumor suppressor genes
 
Oncogenes
OncogenesOncogenes
Oncogenes
 
Chapter 3 hallmarks of cancer
Chapter 3 hallmarks of cancerChapter 3 hallmarks of cancer
Chapter 3 hallmarks of cancer
 
Hereditary Cancer Syndrome
Hereditary Cancer SyndromeHereditary Cancer Syndrome
Hereditary Cancer Syndrome
 

Similar to Cancer genetics

Hereditary Cancer.pptx
Hereditary Cancer.pptxHereditary Cancer.pptx
Hereditary Cancer.pptx
ArdianSusanto4
 
Cancer and tumor markers
Cancer and tumor markersCancer and tumor markers
Cancer and tumor markers
Kshema Thakur
 
Brca acog 2017
Brca acog 2017Brca acog 2017
Brca acog 2017
Rosália Coutada
 
Molecular biology of cancer
Molecular biology of cancerMolecular biology of cancer
Molecular biology of cancer
Nawfal Aldujaily
 
Understanding Cancer: How Genetics Plays a Role
Understanding Cancer: How Genetics Plays a RoleUnderstanding Cancer: How Genetics Plays a Role
Understanding Cancer: How Genetics Plays a Role
kinsleyaniston
 
Cancer
CancerCancer
Cancer
CancerCancer
Precision Medicine and its potential in Cancer management & treatment.pptx
Precision Medicine and its potential in Cancer management & treatment.pptxPrecision Medicine and its potential in Cancer management & treatment.pptx
Precision Medicine and its potential in Cancer management & treatment.pptx
GunjitSetia1
 
1. cancer care.pdf medical surgical nursing 1
1. cancer care.pdf medical surgical nursing 11. cancer care.pdf medical surgical nursing 1
1. cancer care.pdf medical surgical nursing 1
akoeljames8543
 
Development of cancer
Development of cancerDevelopment of cancer
Development of cancer
Merlyn Denesia
 
Breast Cancer And Ovarian Cysts
Breast Cancer And Ovarian CystsBreast Cancer And Ovarian Cysts
Breast Cancer And Ovarian Cysts
Serena Hijazeen
 
Essay On Breast Cancer
Essay On Breast CancerEssay On Breast Cancer
Essay On Breast Cancer
Paper Writing Services Reviews
 
An introduction to cancer
An introduction to cancerAn introduction to cancer
An introduction to cancer
Salman Ul Islam
 
NORMAL-CELLS-versus-CANCER-CELLS.pptxssss
NORMAL-CELLS-versus-CANCER-CELLS.pptxssssNORMAL-CELLS-versus-CANCER-CELLS.pptxssss
NORMAL-CELLS-versus-CANCER-CELLS.pptxssss
RashadHamada
 
Gene therapy
Gene therapyGene therapy
Gene therapy
Mostafa Askar
 
Surviving and Thriving with Gynecologic Cancer - 9.7.19
Surviving and Thriving with Gynecologic Cancer - 9.7.19Surviving and Thriving with Gynecologic Cancer - 9.7.19
Surviving and Thriving with Gynecologic Cancer - 9.7.19
Summit Health
 
Carcinogenesis
CarcinogenesisCarcinogenesis
Carcinogenesis
drmcbansal
 
genetic screening in cancer presentation
genetic screening in cancer presentationgenetic screening in cancer presentation
genetic screening in cancer presentation
venkateshendr
 
Oncology section a
Oncology section aOncology section a
Oncology section a
MUBOSScz
 
Essays On Cancer
Essays On CancerEssays On Cancer
Essays On Cancer
Papers Writing Service
 

Similar to Cancer genetics (20)

Hereditary Cancer.pptx
Hereditary Cancer.pptxHereditary Cancer.pptx
Hereditary Cancer.pptx
 
Cancer and tumor markers
Cancer and tumor markersCancer and tumor markers
Cancer and tumor markers
 
Brca acog 2017
Brca acog 2017Brca acog 2017
Brca acog 2017
 
Molecular biology of cancer
Molecular biology of cancerMolecular biology of cancer
Molecular biology of cancer
 
Understanding Cancer: How Genetics Plays a Role
Understanding Cancer: How Genetics Plays a RoleUnderstanding Cancer: How Genetics Plays a Role
Understanding Cancer: How Genetics Plays a Role
 
Cancer
CancerCancer
Cancer
 
Cancer
CancerCancer
Cancer
 
Precision Medicine and its potential in Cancer management & treatment.pptx
Precision Medicine and its potential in Cancer management & treatment.pptxPrecision Medicine and its potential in Cancer management & treatment.pptx
Precision Medicine and its potential in Cancer management & treatment.pptx
 
1. cancer care.pdf medical surgical nursing 1
1. cancer care.pdf medical surgical nursing 11. cancer care.pdf medical surgical nursing 1
1. cancer care.pdf medical surgical nursing 1
 
Development of cancer
Development of cancerDevelopment of cancer
Development of cancer
 
Breast Cancer And Ovarian Cysts
Breast Cancer And Ovarian CystsBreast Cancer And Ovarian Cysts
Breast Cancer And Ovarian Cysts
 
Essay On Breast Cancer
Essay On Breast CancerEssay On Breast Cancer
Essay On Breast Cancer
 
An introduction to cancer
An introduction to cancerAn introduction to cancer
An introduction to cancer
 
NORMAL-CELLS-versus-CANCER-CELLS.pptxssss
NORMAL-CELLS-versus-CANCER-CELLS.pptxssssNORMAL-CELLS-versus-CANCER-CELLS.pptxssss
NORMAL-CELLS-versus-CANCER-CELLS.pptxssss
 
Gene therapy
Gene therapyGene therapy
Gene therapy
 
Surviving and Thriving with Gynecologic Cancer - 9.7.19
Surviving and Thriving with Gynecologic Cancer - 9.7.19Surviving and Thriving with Gynecologic Cancer - 9.7.19
Surviving and Thriving with Gynecologic Cancer - 9.7.19
 
Carcinogenesis
CarcinogenesisCarcinogenesis
Carcinogenesis
 
genetic screening in cancer presentation
genetic screening in cancer presentationgenetic screening in cancer presentation
genetic screening in cancer presentation
 
Oncology section a
Oncology section aOncology section a
Oncology section a
 
Essays On Cancer
Essays On CancerEssays On Cancer
Essays On Cancer
 

More from Robert J Miller MD

2022 Radiation for Common Cancers
2022 Radiation for Common Cancers2022 Radiation for Common Cancers
2022 Radiation for Common Cancers
Robert J Miller MD
 
Understanding advance directives
Understanding advance directivesUnderstanding advance directives
Understanding advance directives
Robert J Miller MD
 
What’s new in prostate cancer part 2, 2021
What’s new in prostate cancer part 2, 2021What’s new in prostate cancer part 2, 2021
What’s new in prostate cancer part 2, 2021
Robert J Miller MD
 
What’s new in prostate cancer part 1, 2021
What’s new in prostate cancer part 1, 2021What’s new in prostate cancer part 1, 2021
What’s new in prostate cancer part 1, 2021
Robert J Miller MD
 
Smoking and lung cancer and now Covid
Smoking and lung cancer and now CovidSmoking and lung cancer and now Covid
Smoking and lung cancer and now Covid
Robert J Miller MD
 
Music and Aging
Music and AgingMusic and Aging
Music and Aging
Robert J Miller MD
 
Breast cancer 2021
Breast cancer 2021Breast cancer 2021
Breast cancer 2021
Robert J Miller MD
 
Viruses and cancer
Viruses and cancerViruses and cancer
Viruses and cancer
Robert J Miller MD
 
How we eat affects our health
How we eat affects our healthHow we eat affects our health
How we eat affects our health
Robert J Miller MD
 
Cancer imaging
Cancer imagingCancer imaging
Cancer imaging
Robert J Miller MD
 
Happiness in a pandemic
Happiness in a pandemicHappiness in a pandemic
Happiness in a pandemic
Robert J Miller MD
 
Cancer screening for seniors
Cancer screening for seniorsCancer screening for seniors
Cancer screening for seniors
Robert J Miller MD
 
Cancer prevention aspec
Cancer prevention aspecCancer prevention aspec
Cancer prevention aspec
Robert J Miller MD
 
Cancer imaging
Cancer imagingCancer imaging
Cancer imaging
Robert J Miller MD
 
Using the internet to get smarter
Using the internet to get smarterUsing the internet to get smarter
Using the internet to get smarter
Robert J Miller MD
 
Oropharynx cancer and HPV in 2019
Oropharynx cancer and HPV in 2019Oropharynx cancer and HPV in 2019
Oropharynx cancer and HPV in 2019
Robert J Miller MD
 
Cancer prevention
Cancer preventionCancer prevention
Cancer prevention
Robert J Miller MD
 
Prostate Cancer and Gleason Score
Prostate Cancer and Gleason ScoreProstate Cancer and Gleason Score
Prostate Cancer and Gleason Score
Robert J Miller MD
 
Breast cancer staging 2018 video power points
Breast cancer staging 2018 video power pointsBreast cancer staging 2018 video power points
Breast cancer staging 2018 video power points
Robert J Miller MD
 
Screening for prostate cancer 2018
Screening for prostate cancer 2018Screening for prostate cancer 2018
Screening for prostate cancer 2018
Robert J Miller MD
 

More from Robert J Miller MD (20)

2022 Radiation for Common Cancers
2022 Radiation for Common Cancers2022 Radiation for Common Cancers
2022 Radiation for Common Cancers
 
Understanding advance directives
Understanding advance directivesUnderstanding advance directives
Understanding advance directives
 
What’s new in prostate cancer part 2, 2021
What’s new in prostate cancer part 2, 2021What’s new in prostate cancer part 2, 2021
What’s new in prostate cancer part 2, 2021
 
What’s new in prostate cancer part 1, 2021
What’s new in prostate cancer part 1, 2021What’s new in prostate cancer part 1, 2021
What’s new in prostate cancer part 1, 2021
 
Smoking and lung cancer and now Covid
Smoking and lung cancer and now CovidSmoking and lung cancer and now Covid
Smoking and lung cancer and now Covid
 
Music and Aging
Music and AgingMusic and Aging
Music and Aging
 
Breast cancer 2021
Breast cancer 2021Breast cancer 2021
Breast cancer 2021
 
Viruses and cancer
Viruses and cancerViruses and cancer
Viruses and cancer
 
How we eat affects our health
How we eat affects our healthHow we eat affects our health
How we eat affects our health
 
Cancer imaging
Cancer imagingCancer imaging
Cancer imaging
 
Happiness in a pandemic
Happiness in a pandemicHappiness in a pandemic
Happiness in a pandemic
 
Cancer screening for seniors
Cancer screening for seniorsCancer screening for seniors
Cancer screening for seniors
 
Cancer prevention aspec
Cancer prevention aspecCancer prevention aspec
Cancer prevention aspec
 
Cancer imaging
Cancer imagingCancer imaging
Cancer imaging
 
Using the internet to get smarter
Using the internet to get smarterUsing the internet to get smarter
Using the internet to get smarter
 
Oropharynx cancer and HPV in 2019
Oropharynx cancer and HPV in 2019Oropharynx cancer and HPV in 2019
Oropharynx cancer and HPV in 2019
 
Cancer prevention
Cancer preventionCancer prevention
Cancer prevention
 
Prostate Cancer and Gleason Score
Prostate Cancer and Gleason ScoreProstate Cancer and Gleason Score
Prostate Cancer and Gleason Score
 
Breast cancer staging 2018 video power points
Breast cancer staging 2018 video power pointsBreast cancer staging 2018 video power points
Breast cancer staging 2018 video power points
 
Screening for prostate cancer 2018
Screening for prostate cancer 2018Screening for prostate cancer 2018
Screening for prostate cancer 2018
 

Recently uploaded

How to Control Your Asthma Tips by gokuldas hospital.
How to Control Your Asthma Tips by gokuldas hospital.How to Control Your Asthma Tips by gokuldas hospital.
How to Control Your Asthma Tips by gokuldas hospital.
Gokuldas Hospital
 
NARCOTICS- POLICY AND PROCEDURES FOR ITS USE
NARCOTICS- POLICY AND PROCEDURES FOR ITS USENARCOTICS- POLICY AND PROCEDURES FOR ITS USE
NARCOTICS- POLICY AND PROCEDURES FOR ITS USE
Dr. Ahana Haroon
 
What are the different types of Dental implants.
What are the different types of Dental implants.What are the different types of Dental implants.
What are the different types of Dental implants.
Gokuldas Hospital
 
STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7
STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7
STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7
shruti jagirdar
 
Pharmacology of 5-hydroxytryptamine and Antagonist
Pharmacology of 5-hydroxytryptamine and AntagonistPharmacology of 5-hydroxytryptamine and Antagonist
Pharmacology of 5-hydroxytryptamine and Antagonist
Dr. Nikhilkumar Sakle
 
Call Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
Call Girls In Mumbai +91-7426014248 High Profile Call Girl MumbaiCall Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
Call Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
Mobile Problem
 
Travel Clinic Cardiff: Health Advice for International Travelers
Travel Clinic Cardiff: Health Advice for International TravelersTravel Clinic Cardiff: Health Advice for International Travelers
Travel Clinic Cardiff: Health Advice for International Travelers
NX Healthcare
 
Ageing, the Elderly, Gerontology and Public Health
Ageing, the Elderly, Gerontology and Public HealthAgeing, the Elderly, Gerontology and Public Health
Ageing, the Elderly, Gerontology and Public Health
phuakl
 
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
MuskanShingari
 
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdf
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdfOsvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdf
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdf
Osvaldo Bernardo Muchanga
 
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfTest bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
rightmanforbloodline
 
LOW BIRTH WEIGHT. PRETERM BABIES OR SMALL FOR DATES BABIES
LOW BIRTH WEIGHT. PRETERM BABIES OR SMALL FOR DATES BABIESLOW BIRTH WEIGHT. PRETERM BABIES OR SMALL FOR DATES BABIES
LOW BIRTH WEIGHT. PRETERM BABIES OR SMALL FOR DATES BABIES
ShraddhaTamshettiwar
 
Pollen and Fungal allergy: aeroallergy.pdf
Pollen and Fungal allergy: aeroallergy.pdfPollen and Fungal allergy: aeroallergy.pdf
Pollen and Fungal allergy: aeroallergy.pdf
Chulalongkorn Allergy and Clinical Immunology Research Group
 
Post-Menstrual Smell- When to Suspect Vaginitis.pptx
Post-Menstrual Smell- When to Suspect Vaginitis.pptxPost-Menstrual Smell- When to Suspect Vaginitis.pptx
Post-Menstrual Smell- When to Suspect Vaginitis.pptx
FFragrant
 
MRI for Surgeons introduction and basics
MRI for Surgeons  introduction and basicsMRI for Surgeons  introduction and basics
MRI for Surgeons introduction and basics
rohitsharma19711
 
Recent advances on Cervical cancer .pptx
Recent advances on Cervical cancer .pptxRecent advances on Cervical cancer .pptx
Recent advances on Cervical cancer .pptx
DrGirishJHoogar
 
Top Travel Vaccinations in Manchester
Top Travel Vaccinations in ManchesterTop Travel Vaccinations in Manchester
Top Travel Vaccinations in Manchester
NX Healthcare
 
pharmacology for dummies free pdf download.pdf
pharmacology for dummies free pdf download.pdfpharmacology for dummies free pdf download.pdf
pharmacology for dummies free pdf download.pdf
KerlynIgnacio
 
What is Obesity? How to overcome Obesity?
What is Obesity? How to overcome Obesity?What is Obesity? How to overcome Obesity?
What is Obesity? How to overcome Obesity?
Healthmedsrx.com
 
The Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of RespirationThe Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of Respiration
MedicoseAcademics
 

Recently uploaded (20)

How to Control Your Asthma Tips by gokuldas hospital.
How to Control Your Asthma Tips by gokuldas hospital.How to Control Your Asthma Tips by gokuldas hospital.
How to Control Your Asthma Tips by gokuldas hospital.
 
NARCOTICS- POLICY AND PROCEDURES FOR ITS USE
NARCOTICS- POLICY AND PROCEDURES FOR ITS USENARCOTICS- POLICY AND PROCEDURES FOR ITS USE
NARCOTICS- POLICY AND PROCEDURES FOR ITS USE
 
What are the different types of Dental implants.
What are the different types of Dental implants.What are the different types of Dental implants.
What are the different types of Dental implants.
 
STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7
STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7
STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7
 
Pharmacology of 5-hydroxytryptamine and Antagonist
Pharmacology of 5-hydroxytryptamine and AntagonistPharmacology of 5-hydroxytryptamine and Antagonist
Pharmacology of 5-hydroxytryptamine and Antagonist
 
Call Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
Call Girls In Mumbai +91-7426014248 High Profile Call Girl MumbaiCall Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
Call Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
 
Travel Clinic Cardiff: Health Advice for International Travelers
Travel Clinic Cardiff: Health Advice for International TravelersTravel Clinic Cardiff: Health Advice for International Travelers
Travel Clinic Cardiff: Health Advice for International Travelers
 
Ageing, the Elderly, Gerontology and Public Health
Ageing, the Elderly, Gerontology and Public HealthAgeing, the Elderly, Gerontology and Public Health
Ageing, the Elderly, Gerontology and Public Health
 
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
 
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdf
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdfOsvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdf
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdf
 
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfTest bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
 
LOW BIRTH WEIGHT. PRETERM BABIES OR SMALL FOR DATES BABIES
LOW BIRTH WEIGHT. PRETERM BABIES OR SMALL FOR DATES BABIESLOW BIRTH WEIGHT. PRETERM BABIES OR SMALL FOR DATES BABIES
LOW BIRTH WEIGHT. PRETERM BABIES OR SMALL FOR DATES BABIES
 
Pollen and Fungal allergy: aeroallergy.pdf
Pollen and Fungal allergy: aeroallergy.pdfPollen and Fungal allergy: aeroallergy.pdf
Pollen and Fungal allergy: aeroallergy.pdf
 
Post-Menstrual Smell- When to Suspect Vaginitis.pptx
Post-Menstrual Smell- When to Suspect Vaginitis.pptxPost-Menstrual Smell- When to Suspect Vaginitis.pptx
Post-Menstrual Smell- When to Suspect Vaginitis.pptx
 
MRI for Surgeons introduction and basics
MRI for Surgeons  introduction and basicsMRI for Surgeons  introduction and basics
MRI for Surgeons introduction and basics
 
Recent advances on Cervical cancer .pptx
Recent advances on Cervical cancer .pptxRecent advances on Cervical cancer .pptx
Recent advances on Cervical cancer .pptx
 
Top Travel Vaccinations in Manchester
Top Travel Vaccinations in ManchesterTop Travel Vaccinations in Manchester
Top Travel Vaccinations in Manchester
 
pharmacology for dummies free pdf download.pdf
pharmacology for dummies free pdf download.pdfpharmacology for dummies free pdf download.pdf
pharmacology for dummies free pdf download.pdf
 
What is Obesity? How to overcome Obesity?
What is Obesity? How to overcome Obesity?What is Obesity? How to overcome Obesity?
What is Obesity? How to overcome Obesity?
 
The Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of RespirationThe Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of Respiration
 

Cancer genetics

  • 1. Cancer Genetics SHOULD WE ALL GET OUR GENES PROFILED? ASPEC / March 15, 2021 / Robert Miller MD
  • 2.
  • 3. “the fault…is not in our stars but in ourselves”
  • 4. To keep it simple - Are the cancer genes inherited and run in families (germ line and found in every cell in the body) or acquired during life (somatic mutation, and only present in the malignant cells)? - How can you tell them apart and which is more common? - What is the role of a genetic counselor in making sense of a worrisome family history and what tests would they recommend?
  • 6. Is Cancer a Genetic Disease? Since the identification of Oncogenes that could turn normal cell into cancer cells, it’s been assumed that finding and fixing the gene should solve this problem…but It’s more complicated May be more than one gene associated with the cancer May be that conventional genes (protein coding genes) are only part (a small part) of the problem (epigenetics trumps genetics or microbiome genome) May be that cancer is not a genetic problem but a metabolic problem
  • 7. Complexity of Genetics Human Genome Project has also led to a change in our understanding of human traits and how we teach them - one example is eye color. For many years, students were taught that one dominant gene controlled brown or blue eyes In fact, at least ten genes each of which comes in several "flavors," contribute to eye color Other traits are even more complicated; for example, around 80 percent of a person's height is controlled by more than 700 genomic variants, each one having a very small influence. www.genome.gov The human genome contains approximately 3 billion of these base pairs, which reside in the 23 pairs of chromosomes within the nucleus of all our cells. Each chromosome contains hundreds to thousands of genes, which carry the instructions for making proteins. Each of the estimated 30,000 genes in the human genome makes an average of three proteins.
  • 8.
  • 9. Protein coding genes make up only 1.5% of the genome
  • 10. Humans may have far fewer genes than assumed - somewhere between 20,000 to 25,000. That number sounds embarrassingly small considering that nematode worms have about 20,000 too, grapes have about 30,000 and tomatoes have nearly 32,000. Who has more genes, us or a tomato?
  • 11. It’s not this simple! Protein coding genes are a very small part of the picture Tumor Evolution in the Transcriptome, Epigenome, and Epitranscriptome
  • 13. As cancer is evolving there are more changes going on in the epigenetic modifications (methylation) than in the genes themselves All cancers are epigenetically abnormal
  • 14.
  • 15. Maybe cancer is not genetic but metabolic and we should be looking at the mitochondria not the nucleus.
  • 17. Types of genes linked to cancer Tumor suppressor genes. These are protective genes. Normally, they limit cell growth by: •Monitoring how quickly cells divide into new cells •Repairing mismatched DNA •Controlling when a cell dies Examples of tumor suppressor genes include BRCA1, BRCA2, (inherited for breast cancer) and p53 or TP53 (most commonly mutated gene in people with cancer and acquired) Oncogenes. These turn a healthy cell into a cancerous cell. Mutations in these genes are not known to be inherited. Two common oncogenes are: •HER2 •The RAS family of genes DNA repair genes. These fix mistakes made when DNA is copied. Many of them function as tumor suppressor genes. BRCA1, BRCA2, and p53 are all DNA repair genes and may be inherited or acquired
  • 18. Two Questions about Genetics and cancer 1. Did you inherit this (hereditary or germ line). From a blood test or saliva. Tell you what other cancers to expect and the need to have family testing. 2. Did the mutation occur after birth (acquired or somatic), Find this from a genetic analysis of the cancer tissue (biopsy or liquid biopsy) may predict how malignant and what treatment drug options will be effective.
  • 19. For prostate cancer it may be worth testing for inherited mutations (to help predict the course of the disease and for family counseling) and cell molecular genetics (to predict how malignant or aggressive the cancer is, does the patient even need to be treated?)
  • 20.
  • 21. For lung cancer it’s necessary to test for acquired mutations because it will predict which drugs or immunotherapy approached may be useful.
  • 22.
  • 23. Breast Cancer need both for familial or inherited testing (effects management as well as family counseling) and somatic testing (impacts on specific treatment decisions)
  • 24.
  • 25.
  • 26.
  • 27.
  • 28.
  • 29. Paradox that triple negative do better with chemoRx if they are BRCA + , also BRCA do better with PARP inhibitors and the more mutations the more likely to respond to immunotherapy
  • 30. Which is more common, inherited (hereditary) or acquired or somewhere in between? - Sporadic - Familial Cancer - Hereditary Cancer
  • 31. Sporadic Most cancers – 75% to 80% – are sporadic. In sporadic cancer, the gene mutations that cause the cancer are acquired (occur only in the tumor cells, somatic) and are not inherited
  • 32. Genetic analysis of the cancer tissue to find somatic or acquired genetic mutations. EGFR mutation found in lung cancer will guided the physician the three drugs currently approved and effective for cancers with this type of mutation.
  • 33. Familial Cancer Certain common cancers, such as breast, prostate and colon cancers, may occur in more than one member of the same family, thought to be the result of multiple influences. A combination of several genes and other factors, such as diet and exercise, all contribute a small amount to an increased risk of developing cancer. Such families may have a moderately increased risk to develop cancer.
  • 34. Hereditary Cancer Only 5% to 10% of all cancers are hereditary and due to a gene mutation that is present from birth. Usually, the mutation was passed from a mother or father to the child. Because of this, there is usually a recognizable pattern of cancer on one side of the family. There are several clues which suggest that there is hereditary cancer in a family. These can include: - Age of diagnosis is usually younger than in sporadic forms of cancer (often younger than age 50). - Multiple family members have the same or related types of cancer. - Cancer is more likely to develop in more than one site in the body. - Rare cancers may occur, for example, male breast cancer.
  • 35. February 4, 2021 N Engl J Med 2021; 384:440-451
  • 36. Breast Cancer Risk Genes — Association Analysis in More than 113,000 Women Breast Cancer Association Consortium N Engl J Med 2021; 384:428-439 Among European women, approximately 6.8% of the patients and 2.0% of the controls had protein-truncating variants in any of the 9 genes associated with breast cancer risk; in addition, 2.2% of the patients and 1.4% of the controls had missense variants in CHEK2. Estimated Absolute Risk of Breast Cancer Associated with Protein-Truncating Variants in 8 Genes We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls.
  • 37. In the 90% of cancers that are sporadic it takes time to accumulate enough mutations to get cancer
  • 38. In the 10% of cancers that are hereditary every cell starts out with at least one mutation so cancer is more likely and shows up more quickly
  • 39.
  • 40.
  • 41. High-risk syndromic genes are highlighted in green. The moderate-penetrance genes (highlighted in red) have an approximate relative risk of 2.0. The common, low-risk genes are shown in orange. Foulkes, N Engl J Med 2008; 359:2143-2153 Uncommon high risk mutations = hereditary and more common low risk gene mutations = familial
  • 42. A diagram showing the major cancer genes for some cancers. The larger the gene name, the more frequently that gene is defective in that cancer type. Cancer Genes
  • 43. •So far, 291 cancer genes have been reported, more than 1% of all the genes in the human genome. •90% of cancer genes show somatic mutations in cancer, 20% show germline mutations and 10% show both. 2004 Census of Known Cancer Genes Nat Rev Cancer. 2004 Mar; 4(3): 177–183.
  • 45.
  • 46. Cancer risk associated with inherited BRCA1 mutations Risks in women •Breast cancer: The lifetime risk for a women with a BRCA1 mutation is about 65 percent compared to 12.5 percent for an average risk woman. •Ovarian cancer: The lifetime risk for a women with a BRCA1 mutation is about 40 percent compared with 1.3 percent for an average risk woman. •Second breast cancer in women who have already been diagnosed with breast cancer: The lifetime risk is about 40 percent. •Uterine cancer: There is a slightly increased risk for a rare form of aggressive uterine cancer, the estimated risk to age 70 is less than 5 percent Risks in men •Prostate cancer: The lifetime risk for a man with a BRCA1 mutation is about 16 percent compared to 12 percent for an average risk man. Prostate cancers in men with inherited BRCA1 mutations may be more aggressive than in men without an inherited mutation. •Male breast cancer: The lifetime risk for a man with a BRCA1 mutation is about 2 percent. Risks in both men and women •Pancreatic cancer: The lifetime risk for a person with a BRCA1 mutation is about 5 percent compared to 1 percent for an average risk person. •Research on how mutations in the BRCA1 gene affect cancer risk is ongoing. Some research suggests that BRCA1 mutations may increase risk for melanoma. However, because these studies are not conclusive, genetics experts often look at a person’s family history of cancer to help people with BRCA1 mutations understand their risk for additional cancers.
  • 47. In a moving New York Times op-ed,(March 24, 2015) Angelina Jolie Pitt revealed today that she had preventive surgery last week to remove her ovaries and fallopian tubes. The news comes two years after she disclosed that she had a preventive double mastectomy touching off a national conversation about women and cancer risk Jolie Pitt carries a mutation in the BRCA1 gene that gives her an 87% chance of developing breast cancer and a 50% chance of developing ovarian cancer. She lost her mother, grandmother, and aunt to cancer.
  • 48.
  • 49. Odds of having BRCA mutation In the general population : (0.25%) BRCA 1 ( 1 in 300) and BRCA 2 ( 1in 800) Ashkenazi Jewish frequency of either is 1in 40 (2.5%)
  • 50. Non-Ashkenazi Jewish ancestry ●Women with breast cancer (any age): 1 in 50 (2 percent) ●Women with breast cancer (younger than 40 years): <1 in 10 (<10 percent) ●Men with breast cancer (any age): 1 in 20 (5 percent) ●Women with ovarian cancer (any age): 1 in 8 to 1 in 10 (10 to 15 percent) Ashkenazi Jewish ancestry ●Women with breast cancer (any age): 1 in 10 (10 percent) ●Women with breast cancer (younger than 40 years): approximately 1 in 3 (30 to 35 percent) ●Men with breast cancer (any age): 1 in 5 (19 percent) ●Women with ovarian cancer or primary peritoneal cancer (all ages): approximately 1 in 3 (36 to 41 percent)
  • 51. Founder Population Members of the Jewish community who trace their roots to Central or Eastern Europe are known as Ashkenazi Jews. Although today members of this community are found around the world, Ashkenazi Jews for centuries were a geographically isolated population. The isolation experienced by this population means its members can trace their ancestry back to a small number of members known as “founders.”
  • 52. The study in in the journal Nature Communications was funded by the National Institutes of Health and the National Science Foundation, along with several private foundations. Nat. Commun. 5:4835 doi: 10.1038/ncomms5835 (2014).
  • 53. “Ashkenaz” in Hebrew refers to Germany, and Ashkenazi Jews are those who originated in Eastern Europe, no more than half of their DNA comes from ancient Europeans. Those ancient people split off from the ancestors of today’s Middle Easterners more than 20,000 years ago, with a founding group of about 3,500 to 3,900 people. The rest of the Ashkenazi genome comes from the Middle East, this founding group “fused” with the European founding group to create a population of 250 to 420 individuals. These people lived 25 to 32 generations ago, and their descendants grew at a rate of 16% to 53% per generation, the researchers calculated. Previous analyses of recent AJ history highlighted a narrow population bottleneck of only hundreds of individuals in late medieval times, followed by rapid expansion. Today there are more than 10 million Ashkenazi Jews around the world, The AJ population is much larger and/or experienced a more severe bottleneck than other founder populations, such as Amish, Hutterites or Icelanders, whose demographic histories facilitated a steady stream of genetic discoveries. Nat. Commun. 5:4835 doi: 10.1038/ncomms5835 (2014).
  • 54. Final Recommendation Statement BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing August 20, 2019 testing begin with a relative with known BRCA-related cancer or relative with the highest probability of mutation should be tested. Because risk assessment is primarily based on family history, it is unclear how women with a limited or unknown family history should be assessed https://uspreventiveservicestaskforce.org/
  • 55. What do you learn from seeing a genetic counselor?
  • 56. Case study from Genetics Counselor at Mass General https://youtu.be/NRRws1OoT_g
  • 57. Pedigree Chart to map out the family tree
  • 58.
  • 59.
  • 60.
  • 61.
  • 62.
  • 63.
  • 64.
  • 65.
  • 66.
  • 67. Turns out she has BRIP1 (ovarian cancer gene) and HOXB13 (prostate cancer gene)
  • 68. Then her uncle gets tested and he has both so he can screen for prostate cancer
  • 69. Then her brother gets tested and he has prostate so he can screen for prostate cancer
  • 70. Then her cousin gets tested and he is negative for both
  • 71.
  • 72.
  • 73. I wouldn’t really recommend whole exome/genome sequencing for individuals with no medical indication to do so. This does have to do with clinical utility and interpretation of data. As for individuals who are adopted or would like more info about their health, I would recommend looking into some proactive health panels. Options through Invitae are particularly informative and generally affordable. There is even a genetic counseling process available to individuals who’d like to order this testing- https://www.invitae.com/en - all the options https://www.invitae.com/en/staying-healthy - Staying healthy (mainly cancer and cardio) https://www.invitae.com/en/pregnancy- Reproductive/Carrier screening 23andMe is fun information…. Some of the carrier screening is done on their platforms however, they do not do full gene sequencing, but rather targeted mutation analysis. Any findings on 23andMe need to be confirmed by clinical and diagnostic lab. Advice from Deena Whaba the Genetics Counselor at Saint Anthony's
  • 74.
  • 75. https://www.genome.gov/event-calendar/Bold-Predictions-for-Human-Genomics-by-2030 #6 , Genomic Testing will become commonplace like a standard medical test #8, A person’s complete genome will be available on their smart phone in a user friendly format
  • 77. In some cancers like pancreas cancer, the role of family history and genetics may be huge
  • 78. So far (2020) have only identified the relevant gene mutation in less than 20% of the cases
  • 80. High risk genes are rare, lower risk genes are more common
  • 81. Huge individual variation of little or unknown significance
  • 82. Current Status of Pancreas Cancer Genes