Psychological consequences of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC): A prospective follow-up study



Predictive genetic testing for cancer allows identification of those with the mutation (mutation positive) who should undergo cancer surveillance aiming at early detection of cancer and those without the mutation (mutation negative), whose unnecessary worry can be alleviated and who need not undergo frequent surveillance. However, there is a risk that predictive testing might have a harmful emotional impact on an individual. In the course of a predictive genetic testing protocol, we assessed general anxiety (by the State-Trait Anxiety Inventory [STAI]), fear of cancer and death, satisfaction with life and attitude to the future using a questionnaire survey in 271 individuals tested for hereditary non-polyposis colorectal cancer (HNPCC). Measurements were made before the first counseling (baseline), at the test disclosure session (STAI only) and 1 and 12 months after disclosure. Although at every measurement, the mutation-positive individuals were more afraid of cancer than those who were mutation negative, in both groups fear of cancer decreased significantly from baseline after disclosure. The mutation-positive subjects were more anxious than their counterparts immediately after the test disclosure, but the differences had disappeared at the follow-ups. In other variables, neither differences between the groups defined by mutation status nor changes with time were detected. Our findings suggest that counseling and testing relieve fear of cancer; no harmful emotional impact was detectable at the 1-year follow-up. To confirm these findings, however, the impact of testing should be studied after a longer interval. Furthermore, to evaluate the ultimate interpretation of these results, studies are needed to investigate the impact of fear of cancer on surveillance behavior among the mutation-positive subjects. © 2001 Wiley-Liss, Inc.

Hereditary non-polyposis colorectal cancer (HNPCC) is inherited as an autosomal dominant disease with early onset, the mean age at diagnosis of the first (colorectal) cancer being about 45 years.1 HNPCC susceptibility mutations in mismatch repair genes confer a high lifetime risk of cancer (>90%).1, 2 The most common forms of cancer are colorectal cancer (lifetime risk about 80%) and endometrial cancer in women (lifetime risk about 60%). These mutations also confer a higher than expected risk of other cancers, such as gastric, ovarian and urological. Regular surveillance aiming at early detection of tumors substantially reduces mortality and morbidity from colorectal cancer.3–5

Predictive genetic testing for cancer allows identification (in families in which the mutation is known) of those with the mutation (mutation positive) who should undergo cancer surveillance aiming at early detection of cancer and those without the mutation (mutation negative), whose unnecessary worry can be alleviated and who need not undergo frequent surveillance. Thus far, the emotional consequences of genetic testing of HNPCC patients have been reported,6, 7 but very few studies have evaluated these issues during the process of predictive genetic testing in the healthy members of HNPCC families.8, 9 Previously, high levels of satisfaction with the decision to take the predictive test were found 1 year after disclosure in our large series of HNPCC families;8 subsequent observations in the same study setting indicated that utilization of professional psychological help had been minimal and that the majority considered the pre-test and test disclosure rather than the post-test phases important in terms of the need for emotional support.9 These preliminary results suggested good coping after testing.

However, follow-up reports of the emotional consequences of predictive testing for HNPCC, using objective measures, are still lacking. Here we report the results from a prospective questionnaire study with 1-year follow-up performed among 271 members of HNPCC families undergoing a predictive genetic testing protocol, and we analyze the possible association of the result with emotional consequences such as general anxiety, fear of cancer and death, satisfaction with life and attitude to the future. These factors were considered important for estimating emotional well-being and predicting adherence to cancer surveillance.


Testing procedure

During 1995 to 1997, we offered counseling on predictive genetic testing to adults at 50% risk in 36 HNPCC families in which three different mutations of the MLH1 gene had previously been discovered.10, 11 The counseling and testing procedure has been described in detail elsewhere.8, 9 Briefly, all known eligible members of these HNPCC families were informed about the study by letter. Those who consented were invited to an individual pre-test counseling session, which comprised taking the family history and giving information about HNPCC, its mode of inheritance, the gene defect, the nature and risk of colon cancer and other cancers and the methods available for early detection of tumors. The benefits and disadvantages of a predictive gene test were thoroughly discussed, including emotional reactions.

After a 2-week period for reflection, those who chose to take the test signed a consent form and donated a blood sample. Those who declined the test but remained at 50% risk were encouraged to adhere to the clinical cancer surveillance, comprising colonoscopy every 3 years and gynecological examinations for females over 35 years.

Those tested were invited, preferably with an accompanying person, to a post-test counseling session at which the test result and its implications were discussed. For individuals having the mutation, the high risk of colorectal cancer was reiterated, and clinical surveillance was organized. Subjects who did not have the mutation were reminded of the general risk of cancer, to prevent any false reassurance. The result and its interpretation were also given in written form.


The study is based on questionnaires that were mostly filled in by the subjects three times during the procedure: before the first counseling after consent to the study and 1 month and 1 year after the test disclosure. The anxiety scale was also filled in at the test disclosure session, i.e., four times all together.

Study sample

Of the original eligible subjects (n = 446), 90% (n = 401) consented to participate in the study, and 85% (n = 381) returned a baseline questionnaire I.8 The educational counseling session was attended by 347 subjects, of whom 333 (96%; 75% of the total population) opted for a predictive genetic test. Seven tested subjects refused to fill in any further questionnaires. A follow-up questionnaire was sent at 1 month to 326 subjects, of whom 299 (92%) replied. Another follow-up questionnaire was sent at 1 year to these 299 subjects, of whom 271 (91%) filled in this final form.

Thus, the present sample comprised 271 subjects who attended both counseling sessions, took the test and completed the pre- and post-test questionnaires. The characteristics of the study sample have been described elsewhere.9 Of the study subjects, 57% were women, 72% lived with a spouse or partner, 73% had children, 76% were employed and 62% had been educated beyond the primary level. The participants were aged 19 to 77 years (mean 43 years), and 31% (n = 84) of them were mutation positive. The mutation-positive subjects differed from their counterparts in being younger (mean age 37.8 vs. 45.6 years, respectively, p < 0.001). In regard to other background data or to returning the follow-up questionnaires, the two groups of subjects defined by mutation status did not differ. The individuals who were tested but lost to follow-up (n = 62), because they failed to complete the post-test questionnaires, did not differ significantly from the study subjects in any of the background variables.


General anxiety was measured by the state measure of the State-Trait Anxiety Inventory (STAI), which is a 20-item scale.12 The answers to questions are scored on a 4-point scale. Response categories for the items range from 1 (not at all) to 4 (very much so). Scores range from 20 to 80, higher scores indicating greater state anxiety. Cronbach alpha was 0.9 in every measurement, indicating high internal consistency.

Fear of cancer and death were measured with items derived from the Illness Attitude Scale, originally developed by Kellner and translated and culturally adopted by Aro et al.:13 1) Are you afraid of that you may have cancer? 2) Does the thought of death scare you? 3) Are you afraid of dying soon? (0 = no, 1 = rarely, 2 = sometimes, 3 = often, 4 = most of the time).

Attitudes to the future were assessed from answers to a question with the following options: What does your future look like? (1 = extremely negative, 2 = rather negative, 3 = can't say, 4 = fairly promising, 5 = extremely promising). Satisfaction with life was assessed from a question with the following choice of answers: Are you satisfied with your life in general at the moment? (1 = extremely unsatisfied, 2 = rather unsatisfied, 3 = neither satisfied nor unsatisfied, 4 = fairly satisfied, 5 = extremely satisfied).

Statistical analysis

As there was a baseline background difference in age in the groups defined by mutation status, all analyses were adjusted for age. Baseline differences in outcome variables were compared with univariate analysis of covariance, with age as a covariate. Changes in outcome variables with time between and within the groups were analyzed with repeated measures ANCOVA, age being a covariate. Two-tailed p values < 0.05 were considered statistically significant.


Table I presents baseline differences in outcome variables between the groups defined by mutation status after adjusting for age. At baseline, there were significant, albeit small, differences between the groups regarding fear of cancer, fear of dying soon and satisfaction with life. Those who turned out to be mutation positive were initially more afraid of cancer, and more afraid of dying soon, but were also more satisfied with life than their counterparts even after adjusting for age.

Table I. Mean (SD) Scores For Baseline Outcome Variables
VariableMutation-negative group (n = 187)Mutation-positive group (n = 84)p1
  • 1

    Age-adjusted univariate analysis of covariance. ns = nonsignificant.

Anxiety30.9 (7.6)31.6 (8.0)ns
Fear of cancer0.8 (0.9)1.1 (1.0)0.01
Fear of death0.9 (0.9)0.8 (0.9)ns
Fear of dying soon0.3 (0.6)0.4 (0.8)0.02
Perceived health4.1 (0.9)4.1 (0.9)ns
View of the future3.6 (0.7)3.7 (0.7)ns
Satisfaction with life4.0 (0.8)4.2 (0.6)0.01

Figure 1 illustrates the course of anxiety during the study. At the test disclosure session, the mutation-positive subjects who had just received the result had significantly higher scores and the mutation-negative subjects lower scores for anxiety than in the baseline measurement (p <p 0.0001), the difference between the two groups being also significant (p < 0.001). In the later measurements, the mean anxiety scores were similar to the baseline scores in both groups.

Figure 1.

Illustration of the course of age-adjusted mean scores and 95% CI of anxiety (STAI) during the testing procedure. BL, baseline; TDS test disclosure session; 1M, 1-month follow-up; 1Y, 1-year follow-up; circles, mutation negative; squares, mutation positive.

Table II presents the results of change in the outcome variables. After 1 year, the fear of cancer had decreased from baseline in both groups. The mutation-positive subjects were slightly, although significantly, more afraid of cancer at every measurement; however, the difference at baseline was not great, as shown in Figure 2, in which the baseline 95% confidence intervals overlap. No significant time or time/mutation status interactions were found on fear of death, fear of dying soon, attitude to the future or satisfaction with life.

Table II. Mean (SD) Scores for Pre- and Post-test Outcome Variables in the Groups Defined by Mutation Status1
VariableBLTDS1M1YChange in time2Time × mutation status interaction2,3
  • 1

    BL = baseline, TDS = test disclosure session, 1M = 1-month follow-up, 1Y = 1-year follow-up, ns = nonsignificant.

  • 2

    Adjusted for age.

  • 3

    Change with time is different between the groups defined by mutation status.

Anxietynsp < 0.0001
 Mutation-negative (n = 187)30.9 (7.7)28.7 (6.5)30.4 (7.5)30.3 (7.0)
 Mutation-positive (n = 84)31.6 (8.0)35.4 (9.1)31.5 (7.9)30.0 (6.7)
Fear of cancerp = 0.03p = 0.001
 Mutation-negative0.8 (0.9)0.5 (0.8)0.5 (0.7)
 Mutation-positive1.1 (1.0)1.2 (1.0)0.9 (1.0)
Fear of deathnsns
 Mutation-negative0.9 (0.9)0.7 (0.8)0.8 (0.9)
 Mutation-positive0.8 (0.9)0.8 (1.0)0.7 (0.9)
Fear of dying soonnsns
 Mutation-negative0.3 (0.6)0.3 (0.6)0.3 (0.4)
 Mutation-positive0.4 (0.8)0.4 (0.7)0.4 (0.7)
Attitude to the futurensns
 Mutation-negative3.6 (0.7)4.0 (0.6)3.7 (0.6)
 Mutation-positive3.7 (0.7)4.0 (0.7)3.7 (0.7)
Satisfaction with lifensns
 Mutation-negative4.0 (0.8)4.0 (0.6)4.0 (0.7)
 Mutation-positive4.2 (0.6)4.0 (0.7)4.2 (0.6)
Figure 2.

Age-adjusted mean scores and 95% CI for fear of cancer at baseline and at follow-ups. BL, baseline; 1M, 1-month follow-up; 1Y, 1-year follow-up; solid line, mutation positive; dotted line, mutation negative.


We present results of a prospective study of general anxiety, fear of cancer and death, satisfaction with life and attitude to the future in a large series of members of Finnish HNPCC families answering a questionnaire during the process of predictive genetic testing, including 1-month and 1-year follow-up. The fear of cancer decreased significantly, although slightly, over time in both the mutation-positive and the mutation-negative subjects. At the 1-year follow-up, the degrees of anxiety and other fears had not changed significantly from the baseline values, irrespective of the test result. In addition, those tested seemed to view their future as promising and were as satisfied with their lives as before the testing. The study subjects have previously reported consistent high levels of satisfaction with the decision to take the test 1 year after disclosure of the results.8

There were small baseline differences in some outcome variables, such as fear of cancer, which remained even after adjustment for age (Table I) and which we were unable to explain with the variables used in this study. The mutation-positive subjects were more afraid of cancer at every measurement than those who were mutation negative. However, in both groups the fear of cancer decreased with time. In the mutation-negative subjects, this decrease was to be expected, whereas in the mutation-positive subjects it may reflect a sense of security caused by the organized cancer surveillance scheme. A significant portion of the subjects (68%) had already been under cancer surveillance based on high-risk status. The fact that they have been in permanent contact with their HNPCC physician who was readily available may have reduced the fear of cancer and distress. Furthermore, among these individuals, one of the most important reasons for taking a predictive test for HNPCC has been given as reduction of uncertainty;8 perhaps the testing really increased certainty and simultaneously relieved the fear of cancer. A relevant question is, of course, what amount of fear is necessary to induce adherence to cancer surveillance programs but nevertheless be consistent with emotional well-being. Thus far, there are no data available on whether fear of cancer affects surveillance behavior among those who are mutation positive. This issue should be studied in the near future.

Although total general anxiety remained unchanged between baseline and 1-year follow-up, there was a striking difference in anxiety scores between the groups defined by mutation status at the test disclosure measurement. Those receiving bad news were more anxious than those who received good news. Apparently, test disclosure aroused strong feelings, also detected by the anxiety scale, which reflects the degree of excitement at the moment. This accords with the previous opinions of those tested, which revealed that the majority felt the greatest need of psychological support was at the moment of the test disclosure.9 Although all counselees had been recommended to have someone accompanying them at the test disclosure, 70% chose to come alone. It is possible that the counselees might have benefited from an accompanying person from their own social network, who would ideally have helped them to cope with the moment and with the challenges in the future. This also concerns those who received good news, most of whom had lower anxiety scores than at baseline; however, some were anxious despite the normal result. It has been found that high anxiety at the test disclosure session among the mutation-negative subjects seems to predict incorrect comprehension of the test result at follow-up (Aktan-Collan et al., unpublished data).

The study is based on mean values. It should be noted that mean values may mask individual reactions14 and that individual reactions may be quite different.15 Although most of the variables showed no changes with time, the courses of anxiety among our study subjects were diverse and unique (data not shown). This should be taken into consideration in terms of individualized counseling supplemented with the option of ongoing emotional support. The setting at genetic counseling units is suitable for this purpose, in that individual concerns are carefully listened to and discussed and ample time is reserved for each session. In other clinical specialities, the tradition is often different.

Limitations of the study

The counseling and testing were performed in a carefully monitored research setting, which may have increased the sense of security of those participating in the predictive genetic testing program. These results may not be fully applicable in a non-research setting. This study is also based on the responses of the individuals who consented to be tested and returned all three rounds of questionnaires. As noted recently by Broadstock et al.,14 selective dropout over time may cause response bias. It is possible that those tested who failed to return follow-up questionnaires (n = 62) were more anxious than the others. However, we know from baseline data that these dropouts and study subjects were similar with regard to baseline variables and test disclosure anxiety. Furthermore, we checked that all the tested dropouts (except for one who had died naturally) were alive at the 1-year follow-up, thus excluding suicide as a possible extremely adverse consequence of predictive testing.


No signs of harmful emotional effects of testing were detectable by the measures used in the study. At the test disclosure, the mutation-positive subjects had significantly higher anxiety scores than the mutation-negative subjects, but the differences disappeared during follow-up. This should be taken into account in planning the counseling and testing protocol. The testing significantly decreased the fear of cancer from baseline values in both groups defined by mutation status at the 1-year follow-up. Thus, testing seemed to relieve fear of cancer and cause no harmful consequences, at follow-up. However, the emotional impact of testing at longer term should be studied to confirm these findings. Furthermore, studies investigating the impact of fear of cancer on surveillance behavior among those who are mutation positive are needed to evaluate the ultimate interpretation of these results.


We thank Mrs. M. Molin for her contribution to the pre-test counseling.