Download The potential value of genetic data in quality of life research

The potential value of genetic data in
quality of life research in oncology
Present
Francesca Martinelli
?
Quality of Life Department
European Organisation for Research and Treatment of Cancer
EORTC Headquarters
Brussels, Belgium

Europe 2009

Present


Early detection
22 Member States are running or establishing populationbased screening programmes for breast cancer;
15 Member States are running or establishing populationbased screening programmes for cervical cancer;
12 Member States are running or establishing populationbased screening programmes for colorectal cancer.
(Screening programmes…)
Source: European Commission
Diagnosis anticipation
Mortality reduction
Puliti et al (2008): Effectiveness of service screening: a case-control study to
assess breast cancer mortality reduction. Br J Cancer. 2008 Aug 5;99(3):423-7.

Cost

Population

Ethical issues
Present
Present
?
Vaccination
(Papillomavirus…)
Future
Future
?
http://www.webweaver.nu
Future
I everything
Is
thi
written
itt in
i our genes?
?
Genetics

Something at least…
Gregor Mendel (1822-1884)
The “father
father of modern genetics
genetics”
Showed that the inheritance of certain traits in
pea plants follows particular laws.

In his data, Mendel saw approximately a 3:1 ratio of
one phenotype to another.
brown hair
brown hair
brown hair
brown hair
blond hair
brown hair
brown hair
brown hair
brown hair
brown hair
green eyes
green eyes
left-handed
green eyes
green eyes
green eyes
green eyes
green eyes
green eyes
left-handed
left-handed
brown eyes
green eyes
left-handed
left-handed
left-handed
left-handed
left-handed
left-handed
left-handed
right-handed
green eyes
green eyes
brown eyes
green eyes
blond hair
brown hair
brown hair
brown hair

How can genetic and genomic information be
used for risk identification?

Family history

Histological features

Moderate-penetrance genes

Low-penetrance genes

…
Calzone et al (2010): The application of genetics and genomics to cancer
prevention. Semin Oncol. 2010 Aug;37(4):407-18.
left-handed
left-handed
right-handed

What about cancer susceptibility?

Advanced in technology have accelerated the
translation of genetics and genomics into the arena
of cancer prevention (Calzone et al, 2010) and care.

In a near future, not only it may be possible to
identify at-risk individuals, but also to better
understand the underlying biology of the cancer.

Example: candidates for testing for BRAC1
and BRAC2 mutations
Young et al (2009): The prevalence of BRCA1 mutations among young women
with triple-negative breast cancer. BMC Cancer. 2009 Mar 19;9:86.

Genes BRCA1 and BRCA2 are the two major contributors to
hereditary breast cancer.

Genetic testing for these two gene mutations has been
estabilished throughout North America and much of Europe.

In general, testing is offered to a woman that has a
probabilit for being positi
probability
positive
e for a m
mutation
tation ≥ 10%.
10%

Mathematical models can be used to estimate the prior
probability of having a mutation; these models consider ageof-onset and family history of cancer.

However, certain characteristics of breast cancer can also be
used to help predict the presence of a mutation.

Women with triple-negative breast cancer are expected to be
enriched for BRCA1-mutation carriers.

Is our perception of Health-Related Quality of
Life (HRQoL) influenced by genes?

Studies already link genetics and HRQoL, without
linking them.

Growing interest in the subject

Doctors will eventually use genetic patterns for
several tasks: to tell whether a cancer will spread, to
predict how various therapies such as specific
drugs or radiation will work, and perhaps even to
see how someone’s QOL will be affected (Sloan and
Zhao, 2006).

Example: pain
Sprangers et al (2009): The establishment of the GENEQOL consortium to
investigate the genetic disposition of patient-reported quality-of-life outcomes.
Twin Res Hum Genet. 2009 Jun;12(3):301-11.

In this study, the proportion of mutation carriers for these
genes was estimated among women diagnosed at age 40 or
younger with triple-negative breast cancer without a
significant family history of cancer.

N=54 women were studied.

Six deleterious mutations were identified in the 54 patients
(11%): five in BRCA1 and one in BRCA2.

These data support the position that early-onset triplenegative breast cancer is an indicator that can be used to
help to identify candidates for BRCA1 mutation testing.

Young women with a high-grade triple-negative cancer and
no family history of cancer may be candidates for genetic
testing.

Recent research has suggested a genetic
predisposition for some psychological
parameters:

dep ess o
depression

suicide

alcoholism,

smoking,

aggression

…

There are several ways pain perception could be determined
by genes.

Reduced activity of the gene COMT, that mediates the
inactivation of some neurotransmitters (including
adrenaline), has been found to result in increased sensitivity
for pain (Zubieta et al, 2003).

More in general, genes associated with neurotransmission
have been found to be associated with pain perception and
responses to analgesics.

Genes have been found to be involved in the response to
analgesics including absorption, metabolism, distribution
and interaction with targets of analgesics.

Example: chemoradiotherapy-related toxicity

Grade 3 or 4 neutropenia and grade 3 or 4 hematological
toxicity in bladder cancer patients treated with platinumbased chemoradiotherapy were found to be significantly
associated with some common polymorphisms in genes
involved in DNA repair.
Sakano et al (2010): Nucleotide excision repair gene polymorphisms may predict
acute toxicity in patients treated with chemoradiotherapy for bladder cancer.
Pharmacogenomics. 2010 Oct;11(10):1377-87.

Cost

Ethical issues

Paucity of data
[email protected]