2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

and testing include identification of at-risk individuals and
families. In cases where a causative gene mutation can be
identified, mutation-specific testing can identify those individuals
in the family who have inherited the genetic risk
factor and warrant high-risk screening and management.
Single-site mutation testing can also identify those individuals
in the family who did not inherit the condition and,
therefore, are not predicted to be at increased risk and can
forego additional measures. Many family members often
have increased anxiety and worry about the risk for cancer
in the family, and appropriate risk assessment and identification
of a specific cause can provide accurate information
and, in some cases, help to empower family members and
alleviate emotional burden.
There are also potential disadvantages of and obstacles to
cancer genetics evaluations. For example, although the
sensitivity and utility of genetic testing continues to improve,
a causative gene mutation cannot be identified in
some cases even when there is a high suspicion of a specific
diagnosis. Therefore, clinical judgment and expertise must
be applied in these cases to develop an acceptable screening
and management plan for the patient as well as at-risk
family members. In addition, there are also some cases with
striking features of a hereditary cancer syndrome that do
not fit a specific diagnosis or may represent a previously
undescribed syndrome. Research studies as well as advances
in gene finding and exome sequencing may be beneficial in
such cases. However, these newer genomic technologies may
lead to the identification of more variants of unknown
significance for which it can be difficult to counsel the
patient and his or her family. Advancements in genetic
information and testing continue to change at a rapid pace.
Therefore, there needs to be a clear expectation in the
pediatric cancer genetics clinic for periodic follow-up and
recontact with families in the event that new information is
obtained. The results of genetic testing should not stand
alone in risk assessment but rather be one tool in the genetic
cancer risk assessment process.
Ethical and psychosocial considerations remain critical in
the assessment and care of children with potential cancerpredisposition
syndromes. For example, with respect to the
informed consent process, clinicians need to consider the
child’s capacity for autonomy as well as participation in
assent/consent. In addition, much historic debate has occurred
about genetic testing in minors. 46-49 A distinction
between diagnostic and presymptomatic or predictive testing
is relevant. Although diagnostic testing is generally
acceptable in children with features of a genetic condition,
predictive testing is generally reserved for those conditions
for which clinical management would be altered during
childhood. 48 Regarding the psychosocial effects on the family
experience, it is important to explore implications on emotional
well-being, family dynamics, risk perception, influ-
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Table 3. Cancer Genetic Services Resources
Resource Web site
KNAPKE ET AL
National Society of Genetic Counselors
Find a Genetic Counselor Tool
www.nsgc.org
National Cancer Institute http://cancer.gov/cancertopics/genetics/
Cancer Genetic Services Directory directory
ence on other siblings, reproductive decision-making, and
financial consequences.
Because of all of these potential risks and benefits, it is
important that “discussions on genetic testing are done in a
sensitive, comprehensive, and inclusive manner by fully
trained specialist health professionals, such as genetic counselors
and clinical geneticists, in a relaxed and comfortable
environment.” 48 After identifying individuals and families
who might be at increased risk for cancer, referral to a
program with expertise in childhood cancer predisposition is
indicated. Many health care systems may have genetic
counselors or other specialists with genetic expertise on site.
Others may need to seek out and establish appropriate
referral practices to another organization in their area.
Resources for finding local genetic specialists can be found in
Table 3. If cancer genetics services are not available nearby,
an increasing number of programs also offer their services
through a telemedicine service model. When possible, it also
may be beneficial to establish relationships with cancer
genetics programs that practice through a multidisciplinary
approach to care. A growing number of cancer genetics
programs have established specific clinics related to pediatric
cancer predisposition and integrate expertise from clinical
geneticists, pediatric oncologists, and other relevant
subspecialists.
Conclusion
In an era of personalized medicine, identification of disease
susceptibility is no longer solely for academic interest
but is becoming an accepted and clinically relevant element
in the current management of patients. Therefore, it is
imperative for clinicians to recognize those children and
families who will benefit most from a cancer genetics referral,
and assist in the follow-up and management of these
individuals. Although a great deal of knowledge about
cancer-predisposing conditions affecting children now exists,
the scope of genomic information is expanding at a
rapid pace and the future of this field will become increasingly
complex. These new genetic data must be carefully
examined through clinical, translational, and basic research
protocols to ensure their effective translation to the optimized
care of children at increased genetic risk for cancer.
Acknowledgements
K.E.N. acknowledges support in part by the Grundy Vision of
Life Fund. W.K. and J.D.S. acknowledge the use of the Genetic
Counseling Shared Resource supported by P30 CA042014
awarded to Huntsman Cancer Institute.