Introduction: The purpose of this study was to assess the health practices and psychological and demographic characteristics of individuals who are at risk for hereditary nonpolyposis colorectal cancer (HNPCC) who declined to take part in a cost-free genetic testing study for colon cancer. Research subjects, who had at least one first-degree relative diagnosed with colon cancer, were from families registered with the Johns Hopkins Colorectal Cancer Registry.

The reasons that at-risk people declined genetic testing and their demographic characteristics were used to develop predictors of willingness for an at-risk individual to undergo genetic testing. This information could lead to a change in the recruitment of at- risk individuals and improve education about genetic testing and screening.

Hypothesis: The hypotheses for this study were that the individuals who decline gene testing for colon cancer live further from the study testing center than the acceptors, perceive their risk to be lower, see themselves as less able to handle a positive test result, and have had less frequent cancer screening than those who accepted the invitation to participate in the study. In addition, the decliners who asked not to have screening guidelines sent to them are less likely to have had a colonoscopy or flexible sigmoidoscopy.

Background: Research has shown that people at risk for a hereditary cancer have a variety of motivations for undergoing genetic testing. In a 1994 study, individuals at risk for breast cancer expressed interest in testing for a breast cancer-causing gene (BRCA1) because it would alert them about their children's risks, increase their use of screening, and reassure them if the gene test was negative (Lerman 845). In another 1994 study, individuals who underwent genetic testing for a gene mutation that causes Huntington's Disease said that they underwent testing to plan for the future (avoid passing gene to children) and decrease worry about being at risk, regardless of whether the test was positive or negative (Codori 174).

Individuals also indicate many deterrents form undergoing genetic testing. In a 1997 general population study of interest in genetic testing, individuals who were uninterested in testing expressed that they were not worried about having a gene mutation, had no family history of hereditary syndromes, did not think that the test would be accurate, disliked needles, did not have time, or said they were too old (Andrykowski 2142). In a 1995 study, individuals at risk for hereditary breast cancer were concerned about emotional hopelessness, inconclusive tests, loss of insurance, and marital problems that undergoing testing may cause (Lerman 1888). There is also a real risk of employment and insurance discrimination if companies discover an individual is predisposed to a disease by a positive genetic test result (Codori 174).

Studies have shown that there are psychological and demographic predictors influencing whether an at-risk individual will undergo genetic testing. In a 1994 study, women at-risk for breast cancer were offered a cost-free genetic test for BRCA1. Generally, those who declined the test were less educated, perceived themselves as less likely to be a mutation- carrier, perceived themselves to be at lower risk for breast cancer, and worried less about developing breast cancer than those who underwent genetic testing (Lerman 843). In a study of first-degree relatives of colon cancer patients, the decliners of an offered genetic test were older, lived further from the study, perceived themselves to be at lower risk for colon cancer, perceived themselves as less likely to be able to cope with a positive test result, and were less vigilant in their past screening behavior (Codori 2-9). In a number of genetic testing studies, risk perception was correlated with desire to undergo genetic testing (Croyle 284, Lerman 843, Valdimarsdottir 14, Andryowski 2139, Codori 2, Petersen 21). This seems to be the most accurate predictor of uptake of genetic testing. However, those at risk for colon cancer may underestimate their risk (Codori 61). Thus, it is important to examine the reasons at-risk persons give for declining genetic testing, so that those who perceive their risk to be lower than actual can be appropriately educated about cancer prevention.

Methods: A letter of invitation, explaining the genetic testing study, and a return postcard were sent to adult, first-degree relatives of colon cancer patients. Recipients who returned postcards stating no interest in the study, or who did not respond, were contacted for decliner interviews. Decliner interviews consisted of questions about background, concerns about colon cancer, and cancer screening practices. Seventy-five decliner interviews were attempted, fifty-one were completed, fourteen were refused, and eleven people were not reached. If the subjects expressed concern about their colon cancer risk, the interviewer offered phone numbers for cancer resource centers at the end of the interview. If the subjects asked about frequency of cancer screening, the interviewer offered to send screening guidelines to his or her home. Towards the end of the study the author introduced a new protocol, and from that point the interviewer always offered screening guidelines to the participant.

Data Analysis: Data were analyzed using bivariate t-tests in SPSS Version 7.5 for Windows. Acceptor cases were matched to decliner cases for sex and age for the purpose of data analysis. The following questions were analyzed, using the data from decliner and acceptor interviews:

1. What are the reasons decliners give for not participating in the colon cancer genetic testing study? Rationale for Question: By finding out why at-risk people decline genetic testing, it may be possible to improve education about genetic testing and cancer risk so these reasons are acknowledged. Also, it is important to find out whether individuals decline because of logistical reasons (i.e. too far to travel) or psychological reasons (i.e. fear of testing positive), because this information can show whether psychological distress outweighs potential benefits of genetic testing for at-risk individuals.

2. What is the average distance in miles from the study for both groups? Rationale for Question: From this question it is possible to find out whether individuals are more likely to undergo genetic testing if it is close to their homes.

3. What is the perceived risk for the decliners compared to the perceived risk of the acceptors? Rationale for Question: Perceived risk is one of the psychological factors that may distinguish the groups. This question can show how perceived risk is correlated with uptake of genetic testing.

4. What are the levels of worry and thought about colon cancer in the decliners compared to that of the acceptors? Rationale for Question: Worry is another psychological factor that may distinguish the groups. This question can show how cancer-related worry is correlated with uptake of genetic testing.

5. What is the frequency of colonoscopies, sigmoidoscopies, rectal exams, pap smears, and mammograms of the decliners compared to the acceptors? Are the individuals who decline having cancer screening guidelines sent to them more or less likely to have had cancer screening? Rationale for Question: The first question can show whether those who have been screened for colon cancer are more likely to undergo genetic testing than those who have not been screened. The second question can show whether individuals wish to learn about cancer screening and whether people who get regular screening are more or less likely to accept screening guidelines.

6. What is the perception of the decliners and acceptors on their own ability to cope with a positive genetic test result? Rationale for Question: Perception of coping ability is a psychological factor that may distinguish the two groups. It is important to see if acceptors perceive themselves as better able to cope than decliners, since this can show whether individuals decline genetic testing because they do not feel they could cope with a positive test result.

Results: The results showed that the most accurate demographic predictor of willingness to undergo genetic testing was distance from the test center. As shown in Table 1, the acceptors lived an average of 152.5 miles (SD 257.9) from the study versus the decliners who lived an average of 652.7 miles (SD 665.6) from the study (P<.0001). As seen in Table 2, distance was also the reason cited most often by decliners for why they chose not to undergo genetic testing, expressed by 33% of the sample.

As shown in Table 2 and Figure 1, other major reasons for declining genetic testing included cost of travel (11.1%), study requires too much time and energy (7.9%), that the genetic test will not change screening habits (7.9%), or subjects indicated they did not "feel like it" (11.1%).

As shown in Table 3, decliners had a lower perceived risk of developing colon cancer than acceptors. On a scale of 0-100, the mean value for decliners was 16 points lower than that of acceptors (P=.001). As seen in Table 4, decliners perceived themselves as less able to handle a positive test result, again rating themselves an average 16 points lower on a 0-100 scale (P=.003). As shown in Table 5, there was no significance between how much decliners and acceptors thought and worried about getting colon cancer. Both groups rarely thought about getting colon cancer (38.8% of acceptors vs. 47.1% of decliners), and thoughts about colon cancer rarely affected their moods (86.0% acceptors vs. 84.3% decliners) or their ability to perform daily activities (98% for both). The two groups rarely worried about getting colon cancer (80.0% of acceptors vs. 64.8% of decliners).

As seen in Table 6A, acceptors were more likely to have had a colonoscopy or a flexible sigmoidoscopy than the decliners. Of the acceptors, 90.2% had had a colonoscopy versus 58.8% of the decliners (P<.0001). Decliners were less likely to have had a flexible sigmoidoscopy (29.4% vs. 56.9% of the acceptors) (P<.0001). There were no significant differences between decliners and acceptors having rectal exams, fecal occult blood tests, mammograms, or pap smears. As shown in Table 6B, data on whether decliners who had not had a colonoscopy would be less likely to accept cancer screening guidelines were not accurately tested. The sample was too small to give dependable results because the protocol designed to test this was added toward the end of the study.

Conclusions: The purpose of this study was to assess the health practices and psychological and demographic characteristics of at-risk individuals who declined a genetic test for HNPCC. The results of this study confirmed the hypotheses that decliners lived further from the study, perceived their risk to be lower, engaged in fewer endoscopic screening practices (colonoscopies and sigmoidoscopies), and perceived themselves as less able to cope with a positive test result than acceptors. There was no correlation between the amount of thought and worry about colon cancer and likelihood to undergo genetic testing.

Distance from the study was the primary reason cited by decliners for rejecting genetic testing (33.3%). Many who cited distance as their primary reason for declining had secondary and tertiary reasons that reflected their attitude about the actual genetic test, suggesting they may have used distance to cover up more personal reasons for declining.

The decliners' lower perceived risk and lower perceived ability to cope with a positive genetic test result suggest that these individuals may be more psychologically vulnerable to notification of their real risk of developing colon cancer. Since there is no way to accurately assess the actual risk of the participants prior to a genetic test, it is impossible to say which group was more accurate in their predictions. However, it is probable that decliners underestimate their risk to avoid worrying about developing colon cancer.

The acceptors were more likely to have had a colonoscopy or flexible sigmoidoscopy than the decliners. This is not surprising considering that acceptors perceived their risk for getting colon cancer to be higher than the decliners, which may have urged them to have more screening for the disease. The two groups did not differ significantly on usage of fecal occult blood tests, rectal exams, mammograms, or pap smears. This is probably due to the fact that these cancer screening tests are more mainstream than endoscopic screening and are usually done during a routine physical or gynecologic exam.

This study was limited by several factors. First, the study was very homogeneous with respect to race (96% of acceptors and 100% of decliners were white), so results of this study do not represent a cross-sectional view of society. Second, the new screening guideline protocol was added toward the end of this study, so the sample for this analysis was not sufficient to give significant results. Hopefully this new protocol will lead to interesting results that examine whether those who are less likely to be screened for cancer will accept or reject screening guidelines.

In summary, willingness to undergo a genetic test is influenced by both logistical and psychological factors. Individuals who live a long way from the study are more likely to decline an invitation to receive a genetic test than those who live within driving distance. Those who decline a genetic test for HNPCC perceive themselves to be at a lower risk for colon cancer, and perceive themselves to be less able to cope with a positive test result than those who accept. Individuals who have not engaged in endoscopic colon cancer screening are less likely to undergo genetic testing than those who have been screened.

1. Andrykowski Michael A., et al. "Hereditary Cancer Risk Notification and Testing: How Interested is the General Population?" Journal of Clinical Oncology 15.5 (1997): 2139-48.

2. Bond, JH. "Fecal Occult Blood Testing for Colorectal Cancer: Can We Afford Not to Do This?" Colorectal Neoplasia Part I: The Scientific Basis for Current Management 25.4 (1996): 57-70.

3. Burke, Wylie et al. "Recommendations for Follow-up Care of Individuals With an Inherited Predisposition to Cancer." Journal of the American Medical Association 277 (1997): 915-19.

4. Burt, Randall W. "Familial Risk and Colorectal Cancer." Gastroenterology Clinics of North America 25 1996: 793-803, December 1996.

5. Codori Ann-Marie, et al. "Characteristics of Acceptors and Refusers of Predictive Genetic Testing for Familial Adenomatous Polyposis." American Journal of Human Genetics 55 (1994): 808.

6. Codori Ann-Marie et al. "Colon Cancer Risk Factors are Uncorrelated With Colon Cancer Risk." Abstract. American Journal of Human Genetics 61 (1997): A24.

7. Codori, Ann-Marie and Jason Brandt. "Psychological Costs and Benefits of Predictive Gene Testing for Huntington’s Disease." American Journal of Medical Genetics 54 (1994):174-184.

8. Codori, Ann-Marie. "Psychosocial Opporitunities and Hazards in Predictive Testing for Cancer Risk." Colorectal Neoplasia, Part II: Diagnosis and Treatment 26 (1997): 19-39.

9. Codori Ann-Marie, et al. "The Psychology of Cancer Prevention: Colorectal Cancer Risk Assessment Utilization." Unpublished.

10. Croyle, Robert T. and Caryn Lerman. "Interest in Genetic Testing for Colon Cancer Susceptibility: Cognitive and Emotional Correlates." Preventive Medicine 22 (1993): 284-92.

11. Hobbs Patricia, et al. "Acceptors and Rejectors of an Invitation to Undergo Breast Screening Compared to Those who Referred Themselves." Journal of Epidemiological Community Health 34 (1980): 19-22.

12. Lerman Caryn, et al. "Attitudes About Genetic Testing for Breast-ovarian Cancer Susceptibility." Journal of Clinical Oncology 12 (1994): 843-850.

13. Lerman Caryn and Robert T. Croyle. "Genetic Testing for Cancer Predisposition: Behavioral Science Issues. Journal of the National Cancer Institute Monographs 17 (1995): 63-66.

14. Marra, Giancarlo and C. Richard Boland. "Hereditary Nonpolyposis Colorectal Cancer: the Syndrome, the Genes, and Historical Perspectives." Journal of the National Cancer Institute 87 (1995): 1114-1123.

15. Petersen Gloria M., et al. "Attitudes Toward Colon Cancer Gene Testing Among At-risk Relatives." Unpublished.

16. Petersen Gloria M., and Patricia A. Boyd. "Gene Tests and Counseling for Colorectal Cancer Risk: Lessons From Familial Polyposis." Journal of the National Cancer Institute Monographs 17 (1995): 67-71.

17. Petersen, Gloria M. "Genetic Counseling and Predictive Testing for Colorectal Cancer Risk." International Journal of Cancer 69 (1996): 53-54.

18. Valdimarsdottir Howard, et al. "Psychosocial Predictors of Interest in Genetic Testing for Breast Cancer Risk." Annual Meeting American Society of Clinical Oncology, 14 (1995): A1640.