Psychosocial Consequences of DNA Analysis for MEN Type 2

Psychosocial Consequences of DNA Analysis for MEN Type 2

ABSTRACT: Multiple endocrine neoplasia type 2 (MEN-2) is characterized by medullary thyroid carcinoma in combination with pheochromocytomas and, sometimes, parathyroid adenomas. Since 1993, the psychosocial implications of DNA analysis for MEN-2 have been studied in the Netherlands. This article summarizes the first results of that study. Individuals who applied for DNA analysis cited the need to reduce uncertainty as the major reason for wanting the test. An unfavorable test outcome resulted in anxiety and depression but also relief. Immediate preventive treatment was preferred to continued periodic screening. Carriers were preoccupied with disease-related complaints, and identified with other carriers and MEN-2 patients. A favorable test led, in most applicants and partners, to both relief and worry. Some noncarriers felt guilty and isolated from their families. One year after counseling, participants reported fewer psychosomatic complaints. [ONCOLOGY 10(2):141-157, 1996]


Medullary thyroid carcinoma may occur as part of several inherited
cancer syndromes. In addition to medullary thyroid carcinoma,
multiple endocrine neoplasia type 2A (MEN-2A) is characterized
by pheochromocytoma and parathyroid gland hyperplasia or adenoma,
while MEN-2B is associated with pheochromocytoma developmental
anomalies, including marfanoid habitus, mucosal neuromas, and
ganglioneuromatosis of the gut. The only disease phenotype of
familial medullary thyroid carcinoma is medullary thyroid carcinoma.
These syndromes have an autosomal dominant pattern of inheritance
with a high degree of penetrance and variable expression.

Medullary thyroid carcinoma originates in the calcitonin-producing
cells (C-cells) of the thyroid gland. In patients with medullary
thyroid carcinoma or its precursor, C-cell hyperplasia, supranormal
plasma calcitonin levels result from various stimuli. In families
with MEN-2, screening for abnormal plasma calcitonin responses
has allowed surgery to be performed at an early stage, resulting
in improved survival. In MEN-2 families, biochemical manifestations
of medullary thyroid carcinoma generally occur between the ages
of 5 and 25 years (mean, 15 years), before the development of
pheochromocytoma. Thus, the predictive value of clinical tests
depends on the age at which they are performed. Biochemical screening
allows for early detection of tumors, but treatment even at this
stage is not always curative. Knowledge of whether a person is
a gene carrier creates the opportunity for possible preventive

In 1987, the MEN-2 gene was assigned to the pericentromeric region
of chromosome 10 by linkage analysis; this permitted reliable
determination of gene carrier state. In 1993, MEN-2 was shown
to be associated with mutations in the RET proto-oncogene, and
specific RET mutations were detected in MEN-2 families.

In order to validate DNA analysis as an early, reliable method
for identification of MEN-2 gene carriers, the results of DNA
analysis in four large MEN-2 families were compared with the results
of biochemical, radiologic, and pathologic examinations. Histopathologic
examination revealed that all young carriers who had normal plasma
calcitonin test results and who underwent thyroidectomy had small
foci of medullary thyroid carcinoma. Obviously, growth of carcinoma
at a very young age is in accordance with the pathophysiologic
function of the mutated oncogene. In contrast with biochemical
tests, DNA analysis permits unambiguous identification of MEN-2
gene carriers and enables surgery to be performed before medullary
thyroid carcinoma becomes incurable [1,2].

Little is known about the psychosocial implications of DNA analysis.
In MEN-2 families, the youngest generation poses a particularly
important clinical problem. Parents with MEN-2 are especially
concerned about the future health and welfare of their children.
Adaptation of applicants and their family to their newly acquired
risk status is necessary to arrive at a well-considered decision
about screening and treatment.

In the Netherlands, family members at-risk for MEN-2 can apply
for presymptomatic DNA analysis at one of eight clinical genetics
centers. During the first visit to the center, applicants are
informed by a genetic counselor about the disease and its mode
of inheritance, the counseling procedure, and the medical and
psychosocial consequences of the test outcome. After (written)
informed consent is obtained, blood is taken and sent to a laboratory.
During a second appointment, the test outcome is disclosed and
its implications discussed. Applicants with an unfavorable DNA
test outcome can meet the attending physician after counseling.

The major objectives of the present study were to examine the
psychosocial impact of DNA test results and to identify risk factors
for maldadaptive reactions to those results. It was thought that
the study findings would enable genetic counselors to anticipate
psychosocial problems. This article describes the first results
of the study.

Patients and Methods

In 1993, an evaluative study of individuals at risk for MEN-2
was started at the Utrecht University Hospital in cooperation
with the Clinical Genetics Center, Utrecht. After the first visit
to the genetics center, applicants and the person closest to them--usually
the partner or sometimes a parent, if the applicant was an adolescent--were
asked by the clinical geneticist to join the study. The minimum
age of participation was 16 years. Information about children
under age in whom DNA analysis was performed was obtained from
the applying parents. This resulted in data on two groups: (1)
subjects requesting DNA analysis for themselves and (2) parents
applying for their children. Some results of the symptom checklist
(SCL90) that are indicative of psychological distress are presented
in this article.

Data collection was carried out by means of semistructured interviews
and questionnaires 1 week after application (before disclosure
of the test results) and 2 weeks and 1 year after disclosure.

Predisclosure Interview--The first interview (before disclosure)
focused on the applicant's attitude toward DNA analysis. Topics
of examination included: (1) the motivation for applying for testing;
(2) expectations about which test outcome was thought to be most
likely, and what the impact of the disclosure might be; (3) the
perceived threat from genetic testing; (4) the defense against
harmful consequences; and (5) knowledge about the test, disease,
and its mode of inheritance.

First Postdisclosure Interview--In the first interview
after test disclosure, the researcher examined participants' psychological
reactions (eg, anxiety, depression, shock, guilt, relief, and
disbelief) and social effects resulting from disclosure (eg, stigmatization
and altered interpersonal relationships and socioeconomic position).
The interviewer also explored how participants dealt with the
test outcome, especially the way in which they communicated their
feelings to others. Furthermore, participants were asked about
what changes they expected in the near future, what options for
further screening and treatment they favored, and what kind of
support they needed.

Follow-up Interview--The same topics were examined in the
follow-up interview (1 year after disclosure), using the same
methods. At that time, participants also were asked about life
events, changes in their life, and medical treatment they had


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