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Current Status of Genetic Testing for Colorectal Cancer Susceptibility

Current Status of Genetic Testing for Colorectal Cancer Susceptibility

ABSTRACT: Over 130,000 new cases of colon cancer are diagnosed annually. Approximately 20% to 30% of these are attributable to familial risk, and 3% to 5% belong to a hereditary colorectal cancer predisposition syndrome. Recent discoveries of the genes responsible for the inherited colorectal cancer conditions have expanded the field of commercial genetic testing. Health-care providers who use genetic testing in clinical practice are aware of the benefits that genetic testing can confer on screening, prevention, and treatment options for patients with a personal and/or family history of colon cancer. When genetic test results are correctly interpreted, the information they provide can offer medical guidance for the entire family. The psychological impact, however, of presymptomatic testing can be multifaceted. There are unprecedented benefits but also complex issues surrounding genetic testing. For these reasons, the practice of offering genetic testing to individuals at high risk for colon cancer is heavily fortified with guidelines and recommendations. This review covers the current availability and limitations of genetic testing for inherited colorectal cancer syndromes and focuses on guidelines that address the psychological, ethical, and social concerns stemming from genetic testing. [ONCOLOGY 16:161-180,2002]

Colorectal cancer is the
third most common cancer and the
second leading cause of cancer death, after lung cancer, in both men and women.
In 2001, an estimated 135,400 new cases were diagnosed and 56,700 deaths
occurred, accounting for approximately 10% of all cancer deaths.[1] Decades of
research have brought us to the understanding that approximately 20% to 25% of
individuals diagnosed with colorectal cancer have a significant family history
of the disease, and an additional 5% have an inherited colorectal cancer
syndrome.[2] Moreover, the risk of gastrointestinal tract cancer is increased
with the presence of approximately one-third of at least 35 currently known
hereditary cancer syndromes.[3]

Not long after genes were discovered, genetic testing was
integrated into clinical practice. Genetic testing allows for precise definition
of cancer risks vs quantitative estimation of risk derived from population-based
models.[4,5] Commercial genetic testing can also lead to more appropriate
screening, management, and prevention for the patient with a personal or family
history of cancer. However, this evolutionary technology, whether used to
confirm a clinical syndrome or to determine susceptibility, requires thoughtful
consideration of psychological, financial, and ethnocultural values, as well as
the medical necessity for the individual and the family.

With this in mind, our article begins with the principles of
genetic counseling and the guidelines published to ensure quality care of
individuals desiring genetic testing. We also detail the current availability of
and challenges associated with offering genetic testing for the main inherited
colorectal cancer syndromes. This review suggests a framework upon which genetic
testing involving inherited colorectal cancer conditions can be optimized in
modern oncology practice.

Pre- and Posttest Genetic Counseling

Genetic counseling is a process that involves collecting,
documenting, and assessing risk based on personal and family history. The
genetic counselor investigates the known or suspected inherited condition in the
family, determines whether the consultant and other family members are at risk,
interprets medical information and disease course, educates people about the
basic concepts of genetics, provides occurrence and recurrence risks, and
reviews available options including genetic testing. In addition, psychosocial
assessment and interventions are discussed during the course of the counseling

Genetic counseling prior to genetic testing for colorectal
cancer syndromes must include documentation of an accurate personal and family
cancer history and informed consent to either pursue or not pursue testing.
Health-care providers use family information to propose differential diagnoses
of cancer syndromes and to decide whether and what genetic test is appropriate.

Figure 1 and Figure
highlight the possible outcome of test
results and the steps that follow. If test results are interpreted correctly,
information on the entire family is available, and members who are at-risk can
be identified. Highly targeted individual screenings and guidelines can be
developed using the information on specific familial cancers and age of onset of

Although obtaining informed consent is an essential part of
the counseling, it should involve more than just submission of written
permission. The discussion should elicit the consultant’s and the family’s
concerns and expectations as well as perception of risk (if the consultant has
not developed cancer). It should also include a description of the benefits,
limitations, and burdens of genetic testing for specific colorectal cancer
conditions. Reviewing possible test outcomes may help the consultant prepare for
posttest counseling, when the results are learned. The provider can offer
anticipatory guidance based on how the outcome of the genetic test affects
medical surveillance and social/familial relationships.

While the educational and assessment portions of the process
prior to testing are addressed during pretest counseling, posttest counseling
focuses on more sensitive issues surrounding the disclosure of results. Posttest
genetic counseling ensures that the results are accurately interpreted and that
recommendations for medical management, including screening, surgery, and
chemoprevention, are clearly communicated to the consultant and family. A
thoughtful discussion of the consultant’s plans for sharing results and an
assessment of the consultant’s response to results may warrant additional and
appropriate referrals.

Established Guidelines for Genetic Testing

Professional societies have outlined a number of policies
that describe the appropriate manner in which to offer genetic testing in a
clinical setting. The members of these professional organizations include
physicians, geneticists, ethicists, researchers, and others who recognize the
need to address the potential consequences and issues related to predictive

ASCO Recommendations

The American Society of Clinical Oncology (ASCO), a national
medical specialty society representing 10,000 cancer specialists involved in
patient care and clinical research, issued three conditions for genetic testing.
ASCO recommends that cancer predisposition testing be offered only when (1) the
person has a strong family history of cancer or very early onset of disease,
(2) the test can be interpreted adequately, and (3) the test results would
influence the medical screening and management of the patient and family

Cancer Genetics Studies Consortium

The Cancer Genetics Studies Consortium created a task force—a
congregation of members from various medical specialties, social science,
genetic counseling, and consumer advocacy—to provide guidance to clinicians on
the informed-consent process for cancer susceptibility testing. The consensus
statement recommends that the informed consent process should include ongoing
education and counseling sessions. During such sessions, clinicians should be
prepared to elicit the patient’s and/or family’s values, allow for
decision-making to be a shared process, individualize disclosure of information,
and discuss confidentiality, interpretation of results, the potential for
insurance risks and employment discrimination, and alternatives to genetic

The informed consent process may also include a discussion of
other issues pertinent to predictive testing consultation. Psychological outcome
(ie, reaction to receiving positive or negative genetic testing results) covers
an emotional spectrum that includes anger, anxiety, depression, relief, guilt,
and shame.[2] Genetic discrimination could potentially affect such areas as
employability, insurability, and social acceptability.[9] Thus, the potential
benefits of genetic testing must be weighed against the current limitations and
risks associated with this technology.

ASHG/ACMG Statement

Both the American Society of Human Genetics (ASHG) and the
American College of Medical Genetics (ACMG) adopted a position statement on the
age-appropriateness of genetic testing. Generally, testing at-risk members for a
known family mutation can be initiated at the same age as when the at-risk
individual would begin cancer screening and/or medical intervention. The ASHG
and ACMG concur that timely medical benefit to the individual is a primary
justification for offering genetic testing. When minors are involved, the ratio
of psychological and medical benefit to harm must be thoughtfully considered and

The ACMG and ASHG also have published a joint statement on
genetic testing for colon cancer that outlines the process for familial
adenomatous polyposis and hereditary nonpolyposis colorectal cancer.[11]

American Gastroenterological Association Statement

The Amercian Gastroenterological Association (AGA) recently
published a medical position statement on hereditary colorectal cancer and
genetic testing.[12] This guideline and the accompanying technical review on
genetic testing and inherited colorectal cancer syndromes[13] provide a detailed
overview of this topic and are a valuable resource for any clinician who
provides care for these patients.


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