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Genetics of Colorectal Cancer (PDQ®)

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Psychosocial Issues in Hereditary Colon Cancer Syndromes

Introduction
Participation in Genetic Counseling and Testing for Hereditary CRC
        LS
        FAP
Interest in the Use of Assisted Reproductive Technology (ART)
Psychological Impact of Participating in Hereditary CRC Genetic Counseling and Testing
        LS
        FAP
Psychosocial Aspects of Screening and Risk Reduction Interventions for LS and FAP
        Colorectal screening for LS
        Gynecologic cancer screening in LS
        Risk-reducing surgery for LS
        Colorectal screening for FAP
        Risk-reducing surgery for FAP
        Chemoprevention
        Family communication



Introduction

Psychosocial research in cancer genetic counseling and testing focuses on the interest in testing among populations at varying levels of disease risk, psychological outcomes, interpersonal and familial effects, and cultural and community reactions. The research also identifies behavioral factors that encourage or impede surveillance and other health behaviors. Data resulting from psychosocial research can guide clinician interactions with patients and may include the following:

  • Decision-making about risk-reduction interventions, risk assessment, and genetic testing.
  • Evaluation of psychosocial interventions to reduce distress and/or other negative sequelae related to risk notification of genetic testing.
  • Resolution of ethical concerns.

This section of the summary will focus on psychosocial aspects of genetic counseling and testing for Lynch syndrome (LS), familial adenomatous polyposis (FAP), and Peutz-Jeghers syndrome (PJS), including issues surrounding medical screening, risk-reducing surgery, and chemoprevention for these syndromes.

Participation in Genetic Counseling and Testing for Hereditary CRC

LS

There are an increasing number of studies examining the actual uptake of genetic counseling and testing for LS (see Table 16). Studies have included colorectal cancer (CRC) patients and unaffected, high-risk family members, recruited mainly from clinical settings and familial colon cancer registries. Most studies actively recruited participants for free genetic counseling and testing as part of research protocols.[1-8] Participation or uptake was defined at various points in the process, including genetic counseling before testing; provision of a blood sample for testing; and genetic counseling for disclosure of test results.

Table 16. Summary of Prospective Studies Evaluating Participation in Genetic Counseling and Testing for Hereditary Colorectal Cancer (CRC)a,b,c
Syndrome Study Population Nd GC and GT Participatione 
LSAffectedf and unaffectedf members of four extended families from HCCR with a known LS mutation in kindred [3]21959% pretest GC; posttest GC, GT
LSUnaffected FDRs of CRC patients from HCCR [1]50521% pretest GC; 26% pending pretest GC; 15% GT (blood); 4% pending GT (blood)
LSAffected and unaffected members of four extended families from HCCR with a known LS mutation in kindred [2]20847% pretest GC; 43% posttest GC, GT
LSCRC patients from an oncology clinic and HCCR [4]51089% GT (blood)
LSUnaffected members of 36 Finnish families with a known LS mutation in kindred [5]44678% pretest GC; 75% posttest GC, GT
LS and familial CRCAffected and unaffected persons who underwent GC in a high-risk colon cancer clinic [9]57 (LS); 91 (familial CRC)LS: 14% posttest GC, GT
APC I130K: 85% posttest GC, GT
LSCRC patients diagnosed age <60 y with affected FDR or second-degree relative recruited through physicians [6]10147% pretest GC; 36% posttest GC, GT
LSUnaffected FDRs of known LS mutation carriers [7]11151% pretest GC; 50% posttest GC, GT
LSCRC patients from HCCR, relatives, and spouses [8]14026% pretest GC
FAPUnaffected persons from HCCR age >5 y with FAP-affected parent and known APC mutation in family [10]57 adults; 38 minors87% pretest GC; posttest GC, GT (82% adults; 95% minors)

FAP = familial adenomatous polyposis; FDR = first-degree relative; GC = genetic counseling; GT = genetic testing; HCCR = hereditary colon cancer registry; LS = Lynch syndrome.
aAll studies used a prospective, observational design with the exception of one randomized trial evaluating two recruitment methods.[6]
bAll studies offered free GC and GT, with the exception of one study.[9]
cAll studies were conducted in the United States, with the exception of one Finnish study and one German study.[5,8]
dIndicates number of participants older than 18 years, unless otherwise specified.
eGC = participated in pretest or posttest genetic counseling; GT = participated in genetic testing and received results; GT (blood) = only provided blood sample for genetic testing.
fAffected = current or previous CRC diagnosis; Unaffected = no previous diagnosis of CRC.

Participation in both pretest genetic counseling and posttest counseling for disclosure of results ranged from 14% to 59% across studies (see Table 16). The wide range of uptake rates suggests that factors such as cost, test characteristics, and the context in which counseling and testing were offered may have influenced participants’ decisions. For example, among studies that offered free genetic counseling and testing in the context of a research protocol, counseling uptake ranged from 21% to 59%, and testing uptake ranged from 36% to 59%.[1-3,5-8] Most of those who had participated in a free pretest counseling or education session almost always followed through with genetic testing. Further research is needed to evaluate LS genetic counseling and testing participation in the clinical setting.

Although limited in number, these studies offer insight into why individuals from families at risk of LS decide to undergo or decline genetic counseling and testing. Participation in LS genetic counseling was associated with having children, having a greater number of relatives affected by CRC, and greater social support.[6] A study of CRC patients who had donated a blood sample for genetic testing also showed that those who intended to follow through with receiving results were more worried that they carried a LS-predisposing gene mutation, believed that testing would help family members, and more strongly endorsed the benefits and importance of having testing.[4] Factors associated with both counseling and testing uptake included having: children, a greater number of affected relatives, a greater perceived risk of developing CRC, and more frequent thoughts about CRC.[1-3,5-7,11]

Less is known about the characteristics of persons who decide to not undergo LS genetic counseling and testing. Studies have found that persons who declined counseling and testing reported to have a lower perceived risk of CRC,[1] to have fewer first-degree relatives affected with cancer,[7] to be less likely to have had a previous colonoscopy,[1] to have a college education,[2] to have previously participated in cancer genetics research,[2] or to be employed.[5] Psychological factors also may limit the uptake of genetic counseling and testing. Those who declined counseling and testing, especially women, reported a lower perceived ability to cope with mutation-positive test results,[1] and were more likely to report having depressive symptoms.[2] Reasons cited for not seeking genetic counseling or testing have included concerns about potential insurance discrimination, how genetic testing would affect one's family, and how one would emotionally handle genetic test results.[7]

In contrast to the LS genetic counseling and testing uptake studies that have been conducted in the United States, findings from similar studies conducted in other countries may differ. A Finnish study found that 75% of individuals at risk of developing LS underwent genetic testing and counseling for disclosure of test results.[5] Being employed was the only factor that independently predicted test uptake. Fundamental differences between U.S. and Finnish health care systems may have accounted for the substantial differences in testing uptake in this study compared with similar ones conducted in the United States. In particular, the lower likelihood of health or life insurance discrimination in a European state such as Finland may have eliminated an important barrier to testing in that setting.[5]

The majority of these studies that evaluated the uptake of genetic testing for LS have focused on genetic testing for mismatch repair (MMR) mutations associated with this syndrome. Few studies have examined uptake of microsatellite instability (MSI) and immunohistochemical (IHC) testing. One study reported low levels of knowledge and awareness of MSI testing among a sample of CRC patients who met the revised Bethesda guidelines for LS and were offered MSI testing.[12] Patients in this study generally reported positive attitudes about the benefits of MSI testing; however, patients with higher levels of cancer-specific distress also perceived a greater number of barriers to having MSI testing.

Research is emerging on the usefulness of decision aids for LS genetic testing. One study showed that a decision aid, in booklet format, was effective in reducing uncertainty about the testing decision, assisting individuals to make an informed decision about testing, and improving testing knowledge among men. However, the decision aid did not appear to influence actual testing decisions.[13] Another study evaluated the impact of an educational intervention in high-risk CRC patients before MSI and IHC testing but not MMR mutation testing. Patients who received a brief educational session delivered by a health educator plus a CD-ROM decision aid about MSI and IHC testing were found to have greater increases in knowledge about testing, higher satisfaction with preparation for decision-making about testing, lower decisional conflict, and greater decisional self-efficacy compared with patients who received only a brief educational session.[14]

FAP

The uptake for genetic testing for FAP may be higher than testing for LS. A study of asymptomatic individuals in the United States at risk of FAP who were enrolled in a CRC registry and were offered genetic counseling found that 82% of adults and 95% of minors underwent genetic testing.[10] Uptake rates close to 100% have been reported in the United Kingdom.[15] A possible explanation for the greater uptake of APC genetic testing is that it may be more cost-effective than annual endoscopic screening [16] and can eliminate the burden of annual screening, which must often be initiated before puberty. The opportunity to eliminate worry about potential risk-reducing surgery is another possible benefit of genetic testing for FAP. The decision to have APC genetic testing may be viewed as a medical management decision;[17] the potential psychosocial factors that may influence the testing decision are not as well studied for FAP as for other hereditary cancer syndromes. The higher penetrance of APC mutations and earlier onset of disease also may influence the decision to undergo genetic testing for this condition, possibly because of a greater awareness of the disease and more experience with multiple family members being affected.

Genetic testing for FAP is presently offered to children with affected parents, often at the age of 10 to 12 years, when endoscopic screening is recommended. Because it is optimal to diagnose FAP before age 18 years to prevent CRC and because screening and possibly surgery are warranted at the time an individual is identified as an APC mutation carrier, genetic testing of minors is justified in this instance. (Refer to the Testing in children section in the PDQ summary on Cancer Genetics Risk Assessment and Counseling for a more detailed discussion regarding the ethical, psychosocial, and genetic counseling issues related to genetic testing in children.)

In a survey conducted in the Netherlands of members of families with FAP, one-third (34%) believed that it was most suitable to offer APC gene testing to children before age 12 years, whereas 38% preferred to offer testing to children between the ages of 12 and 16 years, when children would be better able to understand the DNA testing process. Only 4% felt that children should not undergo DNA testing at all.[18]

Results of qualitative interview data from 28 U.S. parents diagnosed with FAP showed that 61% favored genetic testing of APC mutations in their at-risk children (aged 10–17 years); 71% believed that their children should receive their test results. The primary reasons why parents chose to test their children included early detection and management, reduction in parental anxiety and uncertainty, and help with decision making regarding surveillance. Reasons provided for not testing focused on discrimination concerns and cost.[19]

Clinical observations suggest that children who have family members affected with FAP are very aware of the possibility of risk-reducing surgery, and focus on the test result as the factor that determines the need for such surgery.[10] It is important to consider the timing of disclosure of genetic test results to children in regard to their age, developmental issues, and psychological concerns about FAP. Children who carry an FAP mutation have expressed concern regarding how they will be perceived by peers and might benefit from assistance in formulating an explanation for others that preserves self-esteem.[10]

Interest in the Use of Assisted Reproductive Technology (ART)

The possibility of transmitting a mutation to a child may pose a concern to families affected by hereditary CRC syndromes to the extent that some carriers may avoid childbearing. These concerns also may prompt individuals to consider using prenatal diagnosis (PND) methods to help reduce the risk of transmission. PND is an encompassing term used to refer to any medical procedure conducted to assess the presence of a genetic disorder in a fetus. Methods include amniocentesis and chorionic villous sampling.[20,21] Both procedures carry a small risk of miscarriage.[20,22] Moreover, discovering the fetus is a carrier of a cancer susceptibility mutation may impose a difficult decision for couples regarding pregnancy continuation or termination and may require additional professional consultation and support.

An alternative to these tests is preimplantation genetic diagnosis (PGD), a procedure used to test fertilized embryos for genetic disorders before uterine implantation.[23,24] Using the information obtained from the genetic testing, potential parents can decide whether or not to implant. PGD can be used to detect mutations in hereditary cancer predisposing genes, including APC.[18,25,26]

From the limited studies published to date, there appears to be interest in the use of ART for FAP, LS, and PJS.[18,25,27,28] However, actual uptake rates have not been reported.

Table 17. Summary of Studies Evaluating Attitudes Toward, Interest in, or Intention to Use Assisted Reproductive Technology (ART) for FAPa, LSb, and PJSa
Study Population  Nc Interest or Intention in ART  Comments 
FAP-affected individuals [25]2095% would consider prenatal GT for FAP; 90% would consider PGD; 75% would consider amniocentesis or chorionic villous sampling
FAP-affected individuals [18]34133% would consider PND for FAP; 30% would consider PGD; 15% felt terminating pregnancy for FAP was acceptable24% and 25% of patients did not respond to questions about attitudes toward PND and PGD, respectively.
Individuals undergoing genetic testing for LS [27]48d21% would consider PND and/or PGD; 19% would consider only PND; 2% would consider only PGDAt 1 year after disclosure of GT results, two of nine mutation carriers reported that they were considering PGD for future pregnancy.
PJS-affected individualsa [28]5215% indicated that pregnancy termination was acceptable if PND identified a fetus with PJS; 52% indicated PGD was acceptable for persons with PJSTen (19%) individuals, nine of whom were female, reported that they had decided not to conceive a child because of PJS.

FAP = familial adenomatous polyposis; GT = genetic testing; LS = Lynch syndrome; PGD = preimplantation genetic diagnosis; PJS = Peutz-Jeghers syndrome; PND = prenatal diagnosis.
aStudies used a cross-sectional design and were conducted in the United States,[25] and in the Netherlands.[18,28].
bParticipants were invited to complete questionnaires before clinical genetic testing for LS and at 3 months and 1 year after disclosure of genetic test results.
cIndicates number of participants older than 18 y, unless otherwise specified.
dRepresents the number who indicated that they were considering having children in the future, out of a total of 130 individuals who answered a questionnaire before genetic testing.[27]

Psychological Impact of Participating in Hereditary CRC Genetic Counseling and Testing

LS

Studies have examined the psychological status of individuals before, during, and after genetic counseling and testing for LS. Some studies have included only persons with no personal history of any LS-associated cancers,[29-32] and others have included both CRC patients and cancer-unaffected persons who are at risk of having a LS mutation.[33-37] Cross-sectional evaluations of the psychosocial characteristics of individuals undergoing LS genetic counseling and testing have indicated that mean pretest scores of psychological functioning for most participants are within normal limits,[33-35] although one study comparing affected and unaffected individuals showed that affected individuals had greater distress and worry associated with LS.[38]

Several longitudinal studies have evaluated psychological outcomes before genetic counseling and testing for LS and at multiple time periods in the year after disclosure of test results. One study examined changes in anxiety based on personal cancer history, gender, and age (younger than 50 years vs. older than 50 years) before and 2 weeks after a pretest genetic-counseling session. Affected and unaffected female participants in both age groups and affected men older than 50 years showed significant decreases in anxiety over time. Unaffected men younger than 50 years maintained low levels of anxiety; however, affected men younger than 50 years showed no reductions in the anxiety levels reported at the time of pretest counseling.[39] A study that evaluated psychological distress 8 weeks postcounseling (before disclosure of test results) among both affected and unaffected individuals found a significant reduction in general anxiety, cancer worry, and distress.[38] In general, findings from studies within the time period immediately after disclosure of mutation status (e.g., 2 weeks to 1 month) suggested that MMR mutation carriers may experience increased general distress,[31,36] cancer-specific distress,[29,30] or cancer worries [36] relative to their pretest measurements. Carriers often experienced significantly higher distress after disclosure of test results than do individuals who do not carry a mutation previously identified in the family (noncarrier).[29-31,36] However, in most cases, carriers’ distress levels subsided during the course of the year after disclosure [31,36] and did not differ from pretest distress levels at 1 year postdisclosure.[29,30] Findings from these studies also indicated that noncarriers experienced a reduction or no change in distress up to 1 year after results disclosure.[29-31,36] A study that included unaffected individuals and CRC patients found that distress levels among patients did not differ between carriers and individuals who received results that were uninformative or showed a variant of unknown significance at any point up to 1 year posttest and were similar compared with pretest distress levels.[37]

A limited number of studies have examined longer-term psychosocial outcomes after LS genetic counseling and testing.[29,40,41] Longitudinal studies that evaluated psychological distress before and after genetic testing found that long-term distress levels (measured at 3 or 7 years posttesting) among mutation carriers and noncarriers were similar to distress levels at baseline.[29,41] with one exception: noncarriers’ cancer-specific distress scores in one study [29] showed a sustained decrease posttesting and were significantly lower than their baseline scores and with carriers’ scores at 1 year posttesting, with a similar trend observed at 3 years posttesting. In one study, carriers were more likely to be worried about CRC risk at 7 years posttesting; however, noncarriers who reported worry about CRC (i.e., “worried to some extent” or “very worried”) were more likely to doubt the validity of their test result than were noncarriers who reported no worry.[41] When asked about their satisfaction with the decision to have testing, the majority of carriers and noncarriers were extremely satisfied up to 7 years posttesting and indicated they would be willing to undergo testing again.[41]

Findings from some studies suggested that there may be subgroups of individuals at higher risk of psychological distress after disclosure of test results, including those who present with relatively higher scores on measures of general or cancer-specific distress before undergoing testing.[33-37,42] A study of CRC patients who had donated blood for LS testing found that higher levels of depressive symptoms and/or anxiety were found among women, younger persons, nonwhites, and those with less formal education and fewer and less satisfactory sources of social support.[33] A subgroup of individuals who showed higher levels of psychological distress and lower quality of life and social support were identified from the same population; in addition, this subgroup was more likely to worry about finding out that they were LS mutation carriers and being able to cope with learning their test results.[34] In a follow-up report that evaluated psychological outcomes after the disclosure of test results among CRC patients and relatives at risk of having a LS mutation, a subgroup with the same psychosocial characteristics experienced higher levels of general distress and distress specific to the experience of having genetic testing within the year after disclosure, regardless of mutation status. Nonwhites and those with lower education had higher levels of depression and anxiety scores at all times compared with whites and those with higher education, respectively.[36] Other studies have also found that a prior history of major or minor depression, higher pretest levels of cancer-specific distress, having a greater number of cancer-affected first-degree relatives, greater grief reactions, and greater emotional illness–related representations predicted higher levels of distress from 1 to 6 months after disclosure of test results.[37,42] While further research is needed in this area, case studies indicate that it is important to identify persons who may be at risk of experiencing psychiatric distress and to provide psychological support and follow-up throughout the genetic counseling and genetic testing process.[43]

Studies also have examined the effect of LS genetic counseling and testing on cancer risk comprehension. One study reported that nearly all mutation carriers and noncarriers could accurately recall the test result 1 year after disclosure. More noncarriers than carriers correctly identified their risk of developing CRC at both 1 month and 1 year after result disclosure. Mutation carriers who incorrectly identified their CRC risk were more likely to have had lower levels of pretest subjective risk perception compared with those who correctly identified their level of risk.[31] Another study reported that accuracy of estimating colorectal and endometrial cancer risk improved after disclosure of mutation status in carriers and noncarriers.[32]

FAP

Studies evaluating psychological outcomes after genetic testing for FAP suggest that some individuals, particularly mutation carriers, may be at risk of experiencing increased distress. In a cross-sectional study of adults who had previously undergone APC genetic testing, those who were mutation carriers exhibited higher levels of state anxiety than noncarriers and were more likely to exhibit clinically significant anxiety levels.[44] Lower optimism and lower self-esteem were associated with higher anxiety in this study,[44] and FAP-related distress, perceived seriousness of FAP, and belief in the accuracy of genetic testing were associated with more state anxiety among carriers.[45] However, in an earlier study that compared adults who had undergone genetic testing for FAP, Huntington disease, and hereditary breast/ovarian cancer syndrome, FAP-specific distress was somewhat elevated within 1 week after disclosure of either positive or negative test results and was lower overall than the other syndromes.[17]

In a cross-sectional Australian study focusing on younger adults aged 18 to 35 years diagnosed with FAP (N = 88), participants most frequently reported the following FAP-related issues for which they perceived the need for moderate-to-high levels of support or assistance: anxiety regarding their children’s risk of developing FAP, fear about developing cancer, and uncertainty about the impact of FAP.[46] Seventy-five percent indicated that they would consider prenatal testing for FAP; 61% would consider PGD, and 61% would prefer that their children undergo genetic testing at birth or before age 10 years. A small proportion of respondents (16%) reported experiencing some FAP-related discrimination, primarily indicating that attending to their medical or self-care needs (e.g., time off work for screening, need for frequent toilet breaks, and physical limitations) may engender negative attitudes in colleagues and managers.

Another large cross-sectional study of FAP families conducted in the Netherlands included persons aged 16 to 84 years who either had an FAP diagnosis, were at 50% risk of having an APC mutation, or were proven APC noncarriers.[47] Of those who had APC testing, 48% had done so at least 5 years or longer before this study. Of persons with an FAP diagnosis, 76% had undergone preventive colectomy, and 78% of those were at least 5 years postsurgery. The study evaluated the prevalence of generalized psychological distress, distress related specifically to FAP, and cancer-related worries. Mean scores on the Mental Health Index-5, a subscale of the SF-36 that assessed generalized distress, were comparable to the general Dutch population. Twenty percent of respondents were classified as having moderate to high levels of FAP-specific distress as measured by the Impact of Event scale (IES), with 23% of those with an FAP diagnosis, 11% of those at risk of FAP, and 17% of noncarriers reporting scores in this range. Five percent reported scores on the IES that indicated severe and clinically relevant distress; of those, the majority (78%) had an FAP diagnosis. Overall, mean scores on the Cancer Worry Scale were comparable to those found in another study of families with LS. Persons with an FAP diagnosis were more likely to report more frequent cancer worries, and the most commonly reported worries were the potential need for additional surgery (26%) and the likelihood that they (17%) or a family member (14%) will develop cancer. In multivariate analysis, factors associated with higher levels of FAP-specific distress included greater perceived risk of developing cancer, more frequent discussion about FAP with family or friends, and having no children. Factors associated with higher levels of cancer-specific worries included being female, poorer family functioning, greater actual and desired discussion about FAP with family or friends, greater perceived cancer risk, poorer general health perceptions, and having been a caregiver for a family member with cancer. The authors noted that most factors that were associated with higher levels of cancer- and FAP-specific distress or worry were psychosocial factors, rather than clinical or demographic factors.

Another cross-sectional study conducted in the Netherlands found that among FAP patients, 37% indicated that the disease had influenced their desire to have children (i.e., wanting fewer or no children). Thirty-three percent indicated that they would consider PND for FAP; 30% would consider PGD. Higher levels of guilt and more positive attitudes towards terminating pregnancy were associated with greater interest for both PND and PGD.[18] In a separate U.S. study, predictors of willingness to consider prenatal testing included having an affected child and experiencing a first-degree relative’s death secondary to FAP.[25]

The psychological vulnerability of children undergoing testing is of particular concern in genetic testing for FAP. Research findings suggest that most children do not experience clinically significant psychological distress after APC testing. As in studies involving adults, however, subgroups may be vulnerable to increased distress and would benefit from continued psychological support. A study of children who had undergone genetic testing for FAP found that their mood and behavior remained in the normal range after genetic counseling and disclosure of test results. Aspects of the family situation, including illness in the mother or a sibling were associated with subclinical increases in depressive symptoms.[48] In a long-term follow-up study of 48 children undergoing testing for FAP, most children did not suffer psychological distress; however, a small proportion of children tested demonstrated clinically significant posttest distress.[49] Another study found that although APC mutation–positive children’s perceived risk of developing the disease increased after disclosure of results, anxiety and depression levels remain unchanged in the year after disclosure.[44] Mutation-negative children in this study experienced less anxiety and improved self-esteem over this same time period.

Psychosocial Aspects of Screening and Risk Reduction Interventions for LS and FAP

Colorectal screening for LS

Benefits of genetic counseling and testing for LS include the opportunity for individuals to learn about options for the early detection and prevention of cancer, including screening and risk-reducing surgery. Studies suggest that many persons at risk of LS may have had some CRC screening before genetic counseling and testing, but most are not likely to adhere to LS screening recommendations. Among persons aged 18 years or older who did not have a personal history of CRC and who participated in U.S.-based research protocols offering genetic counseling and testing for LS, between 52% and 62% reported ever having had a colonoscopy before genetic testing.[1,3,50,51] Among cancer-unaffected persons who participated in similar research in Belgium and Australia, 51% and 68%, respectively, had ever had a colonoscopy before study entry.[32,52] Factors associated with ever having a colonoscopy before genetic testing included higher income and older age,[50] higher perceived risk of developing CRC,[52] higher education level, and being informed of increased risk of CRC.[51]

In a study of cancer-affected and cancer-unaffected persons who fulfilled clinical criteria for LS, 92% reported having had a colonoscopy and/or flexible sigmoidoscopy at least once before genetic testing.[53] Another study of unaffected individuals presenting for genetic risk assessment and possible consideration of LS, FAP, or APC I1307K genetic testing reported that 77% had undergone at least one screening exam (either colonoscopy, flexible sigmoidoscopy, or barium enema).

Three studies determined whether cancer-unaffected persons adhered to LS colonoscopy screening recommendations before genetic testing, and reported adherence rates of 10%,[32] 28%,[51] and 47%.[53]

Several longitudinal studies examined the use of screening colonoscopy by cancer-unaffected persons after undergoing testing for a known LS mutation.[32,50-52] These studies compared colonoscopy use before LS genetic testing with colonoscopy use within 1 year after disclosure of test results. One study reported that LS mutation carriers were more likely to have a colonoscopy than were noncarriers and those who declined testing (73% vs. 16% vs. 22%) and that colonoscopy use increased among carriers (36% vs. 73%) in the year after disclosure of results.[51] Two other studies reported that carriers’ colonoscopy rates at 1 year after disclosure of results (71% and 53%) were not significantly different from rates before testing,[50,52] although noncarriers’ colonoscopy rates decreased in the same time period. Factors associated with colonoscopy use at 1 year after disclosure of results included carrying a LS-predisposing mutation,[50-52] older age,[50] and greater perceived control over CRC. These findings suggest that colonoscopy rates increase or are maintained among mutation carriers within the year after disclosure of results and that rates decrease among noncarriers. Data from a longitudinal study including 134 MMR mutation carriers with and without a prior LS-related cancer diagnosis found that those who did not undergo colonoscopy for surveillance within 6 months after receiving genetic test results were six times more likely to report clinically significant depressive symptoms as measured by the Center for Epidemiological Studies-Depression (CES-D) scale (odds ratio [OR], 6.06; 95% confidence interval [CI], 2.09–17.59). Higher levels of CRC worry measured before genetic testing also were associated with clinically significant depressive symptoms (OR, 1.53; 95% CI, 1.19–1.97).[54]

Two studies examined the level of adherence to published screening guidelines after LS genetic testing, based on mutation status. One study reported a colonoscopy adherence rate of 100% among mutation carriers.[32] Another study found that 35% of mutation carriers and 13% of noncarriers did not adhere to published guidelines for appropriate CRC screening;[50] in both groups, about one-half screened more frequently than published guidelines recommend, and one-half screened less frequently.

The longitudinal studies described above examined colorectal screening behavior within a relatively short period of time (1 year) after receiving genetic test results, and less is known about longer-term use of screening behaviors. A longitudinal study (N = 73) that examined psychological and behavioral outcomes among cancer-unaffected persons at 3 years after disclosure of genetic test results found that all carriers (n = 19) had undergone at least one colonoscopy between 1 and 3 years postdisclosure.[29] A longitudinal study of similar outcomes up to 7 years posttesting also found that all carriers had undergone colonoscopy; most (83%) underwent the procedure every 3 years or more frequently as recommended, and 11% reported longer screening intervals.[41] In this study, those who reported longer screening intervals than recommended also were more likely to report a fear of dying soon. Also, 16% of noncarriers reported undergoing colonoscopy within the 7 years posttesting; those who indicated doubts about the validity of their test result were more likely to have had a colonoscopy.[41] Ninety-four percent of carriers in one study stated an intention to have annual or biannual colonoscopy in the future; among noncarriers, 64% did not intend to have colonoscopy in the future or were unsure, and 33% intended to have colonoscopy at 5- to 6-year intervals or less frequently.[32] A cross-sectional study conducted in the Netherlands examined the use of flexible sigmoidoscopy or colonoscopy among persons with CRC, endometrial cancer, or a clinical or genetic diagnosis of LS during a time that ranged from 2 years to 18 years after risk assessment and counseling.[55] Eighty-six percent of LS mutation carriers, 68% of those who did not test or who had an uninformative LS genetic test result, and 73% of those with a clinical LS diagnosis were considered adherent with screening recommendations, based on data obtained from medical records. Participants also answered questions regarding screening adherence, and 16% of the overall sample reported that they had undergone screening less frequently than recommended. For the overall sample, greater perceived barriers to screening were associated with screening nonadherence as determined through medical record review, and embarrassment with screening procedures was associated with self-reported nonadherence. A second cross-sectional study, also conducted in the Netherlands, surveyed cancer-unaffected LS mutation carriers (n = 42) regarding their colorectal screening behaviors after learning their mutation status (range, 6 months–8.5 years). Thirty-one percent of respondents reported that they had undergone annual colonoscopy before LS genetic testing, and 88% reported that they had undergone colonoscopy since their genetic diagnosis (P < .001).[40]

Gynecologic cancer screening in LS

Several small studies have examined the use of screening for endometrial and ovarian cancers associated with LS (see Table 18). There are several limitations to these studies, including small sample sizes, short follow-up, retrospective design, reliance on self-report as the data source, and some not including patients who had undergone LS genetic testing. Several studies have included individuals in the screening uptake analysis who do not meet the minimum age criteria for undergoing screening. Of the studies that assessed screening use after a negative test result for a known mutation in the family, only a few assessed indications for that screening, such as follow-up of a previously identified abnormality. Last, some studies have included patients in the uptake analysis who were actively undergoing treatment for another cancer, which could influence provider screening recommendations. Therefore, Table 18 is limited to studies with patients who had undergone LS genetic testing, larger sample sizes, longer follow-up, and analysis that included individuals of an appropriate screening age.

Table 18. Uptake of Gynecologic Screening Among Women Who Have Undergone Lynch Syndrome (LS) Genetic Testing
Study Citation Study Population Uptake of Gynecologic Screening Before Genetic Counseling and Testing Uptake of Gynecologic Screening After Receipt of Genetic Test Results Length of Follow-up Comments 
Claes et al. (2005)1,a [32]Carriers (n = 7)Not reportedTVUS 1 yOne noncarrier reported undergoing TVUS for a previous endometrial problem, while three noncarriers reported undergoing the procedure for preventive reasons.
– Carriers 86% (6/7)
Noncarriers (n = 16)
– Noncarriers 27% (4/15)
Collins et al. (2007)1,a [29]Carriers (n = 13)Not reportedTVUS 3 yTwo of four carriers had an RRH/RRSO by the 3-year follow-up assessment.
– Carriers 69% (9/13)
– Noncarriers 6% (2/32)
Noncarriers (n = 32)ES
– Carriers 54% (7/13)
– Noncarriers 3% (1/32)
Yurgelun et al. (2012): Cohort 12,a [56]77 at risk of LS-associated EC; 45 carriers; 19 no genetic testing but LS-associated family history75% (58/77) engaged in EC screening or EC risk-reduction intervention; 42 underwent annual TVUS and/or ES; 16 underwent RRHNot reportedN/A
Yurgelun et al. (2012): Cohort 21,a [56]40 women at clinical risk of LS65% (26/40) adhered to EC screening or risk reduction; 6 underwent RRH; 13 underwent annual ES and/or TVUS; 6 had not reached recommended screening ageCarriers: 100% (n = 16) adhered to EC screening or risk-reducing strategies; 4 underwent pretest RRH; 5 underwent RRH; 5 underwent EC screening (TVUS and/or ES); 2 had not reached recommended screening age1 y
Carriers (n = 16)
Noncarriers (n = 9); 14 indeterminate results; 1 variant of uncertain significanceNoncarriers: 11% (1/9) underwent EC screening; 11% (1/9) underwent RRH

EC = endometrial cancer; ES = endometrial sampling; RRH = risk-reducing total abdominal hysterectomy; RRSO = risk-reducing salpingo-oophorectomy; TVUS = transvaginal ultrasound.
Noncarrier(s) = negative for known mutation in family.
1Prospective study design.
2Retrospective study design.
aSelf-report as data source.

Overall, these studies have included relatively small numbers of women and suggest that screening rates for LS-associated gynecologic cancers are low before genetic counseling and testing. However, after participation in genetic education and counseling and the receipt of LS mutation test results, uptake of gynecologic cancer screening in carriers generally increases, while noncarriers decrease use.

Risk-reducing surgery for LS

There is no consensus regarding the use of risk-reducing colectomy for LS, and little is known about decision-making and psychological sequelae surrounding risk-reducing colectomy for LS.

Among persons who received positive test results, a greater proportion indicated interest in having risk-reducing colectomy after disclosure of results than at baseline.[3] This study also indicated that consideration of risk-reducing surgery for LS may motivate participation in genetic testing. Before receiving results, 46% indicated that they were considering risk-reducing colectomy, and 69% of women were considering risk-reducing total abdominal hysterectomy (RRH) and risk reducing bilateral salpingo-oophorectomy (RRSO); however, this study did not assess whether persons actually followed through with risk-reducing surgery after they received their test results. Before undergoing LS genetic counseling and testing, 5% of cancer-unaffected individuals at risk of a MMR mutation in a longitudinal study reported that they would consider colectomy, and 5% of women indicated that they would have an RRH and an RRSO, if they were found to be mutation-positive. At 3 years after disclosure of results, no participants had undergone risk-reducing colectomy.[29,52] Two women who had undergone an RRH before genetic testing underwent RRSO within 1 year after testing,[52] however, no other female mutation carriers in the study reported having either procedure at 3 years after test result disclosure.[29]

In a cross-sectional quality-of-life and functional outcome survey of LS patients with more extensive (subtotal colectomy) or less extensive (segmental resection or hemicolectomy) resections, global quality-of-life outcomes were comparable, although patients with greater extent of resection described more frequent bowel movements and related dysfunction.[57]

Colorectal screening for FAP

Less is known about psychological aspects of screening for FAP. One study of a small number of persons (aged 17–53 years) with a family history of FAP who were offered participation in a genetic counseling and testing protocol found that among those who were asymptomatic, all reported undergoing at least one endoscopic surveillance before participation in the study.[53] Only 33% (two of six patients) reported continuing screening at the recommended interval. Of the affected persons who had undergone colectomy, 92% (11 of 12 patients) were adherent to recommended colorectal surveillance. In a cross-sectional study of 150 persons with a clinical or genetic diagnosis of classic FAP or attenuated FAP (AFAP) and at-risk relatives, 52% of those with FAP and 46% of relatives at risk of FAP, had undergone recommended endoscopic screening.[58] Among persons who had or were at risk of AFAP, 58% and 33%, respectively, had undergone screening. Compared with persons who had undergone screening within the recommended time interval, those who had not screened were less likely to recall provider recommendations for screening, more likely to lack health insurance or insurance reimbursement for screening, and more likely to believe that they are not at increased risk of CRC. Only 42% of the study population had ever undergone genetic counseling. A small percentage of participants (14%–19%) described screening as a “necessary evil,” indicating a dislike for the bowel preparation, or experienced pain and discomfort. Nineteen percent reported that these issues might pose barriers to undergoing future endoscopies. Nineteen percent reported that improved techniques and the use of anesthesia have improved tolerance for screening procedures.

Risk-reducing surgery for FAP

When persons at risk of FAP develop multiple polyps, risk-reducing surgery in the form of subtotal colectomy or proctocolectomy is the only effective way to reduce the risk of CRC. Most persons with FAP can avoid a permanent ostomy and preserve the anus and/or rectum, allowing some degree of bowel continence. (Refer to the Interventions for FAP section of this summary for more information about surgical management procedures in FAP.) Evidence on the quality-of-life outcomes from these interventions continues to accumulate and is summarized in Table 19.

Table 19. Studies Measuring Quality-of-Life Variables in Familial Adenomatous Polyposis (FAP)
Population  Length of Follow-up Type of Procedure Stool Frequency Stool Continency Body Image Sexual Functioning Comments 
279 FAP-affected individuals (135 females and 144 males) after colectomy; controls included 1,771 individuals from the general Dutch population [59]IRA mean: 12 y (SD, 7.5 y)IRA: n = 161Not assessedNot assessedEORTC QLQ-CR38 a EORTC QLQ-CR38 a SF-36b scores (Dutch version) on all subscales were significantly lower than the scores in the general population (IRA: P < .001; IPAA: P < .001).
IRA: 87.5 (SD, 21.9)IRA: 38.9 (SD, 26.6)
IPAA mean: 6.8 y (SD, 4.9 y)IPAA: n = 118IPAA: 84.4 (SD, 22.7)IPAA: 42.2 (SD, 26.3)
88 Australian individuals (63 females and 25 males) aged 18–35 y, including 57 after colectomy and 14 with FAP but no surgery [60]Not reportedIRA: n = 33Not assessedNot assessedSF-36 b SF-36 b
IPAA: n = 21IRA: 89.9 (SD, 16.1)IRA: 86.2 (SD, 21.6)
Ileostomy: n = 1IPAA: 72.1 (SD, 23)IPAA: 77.5 (SD, 26.2)
Unknown surgery type: n = 2No surgery: 94.1 (SD, 9.4)No surgery: 91 (SD, 19)
525 individuals (283 females and 242 males) including 296 after colectomy, 45 with FAP but no surgery, 50 at risk for FAP and no surgery, and 134 noncarriers [61]Range: 0–1 y to >10 yIRA: n = 136Not assessedNot assessedEORTC QLQ-CR38 a EORTC QLQ-CR38 a 41% of FAP patients reported employment disruptions:
After colectomy: 85.4 (SD, 20.5)After colectomy: 42.2 (SD, 23.2)Part or complete disability: n = 73 (59%)
IPAA: n = 112FAP no surgery: 91.9 (SD, 16.1)After colectomy: 42.2 (SD, 23.2)Worked less: n = 30 (24%)
Ileostomy: n = 42At risk: 94.0 (SD, 13.1)At risk: 47.6 (SD, 23.7)Worked more n = 5 (4%)
Other: n = 6Noncarrier: 92.3 (SD, 13.1)Noncarrier: 45.7 (SD, 21.2)Worked more or less at different periods: n = 16 (13%)
209 Swedish FAP-affected individuals (116 females and 93 males) after colectomy aged 18–75 y [62]Mean time since last surgery: 14 y (SD, 10; range, 1–50 y)IRA: n = 71Not assessedDay: 71% (n = 149)Not assessedNot assessedThe mean number of 21 abdominal symptoms assessed was 7 (SD, 4.61; range, 1–18). Women reported more symptoms than men, but there were no differences between genders regarding the degree the symptoms were troublesome. Higher symptom number was an independent predictor of poorer physical and mental health.
IPAA: n = 82
Ileostomy: n = 39Night: 61% (n = 128)
Continent ileostomy: n = 14
Other: n = 3
28 individuals (10 females and 18 males) who underwent colectomy at age 14 y or younger [63]12 y (SD, 8.4; range, 1–37 y)IRA: n = 7Day:Day:Rosenberg self-esteem score : 25.53/30cNot assessed10/28 reported cancer-related worry post colectomy, with a trend that young age (<18 y) was associated with more cancer-related worry.
IRA: 3.8 (SD, 1.5)IRA: 71.4% (n = 7)
IPAA: 5.3 (SD, 2.4)IPAA: 85.7% (n = 21)
IPAA: n = 21Night:Night:
IRA: 1.3 (SD, 0.6)IRA: 50.0% (n = 7)
IPAA: 1.3 (SD, 0.5)IPAA: 61.9% (n = 21)

EORTC QLQ = European Organization for Research and Treatment of Cancer Colorectal Quality of Life Questionnaire; IPAA = ileal pouch-anal anastomosis; IRA = ileorectal anastomosis; SD = standard deviation; SF-36 = Short Form (36) Health Survey.
a EORTC QLQ-C38 scores range from 0–100. Functional scales: 0 = lowest level of function and 100 = highest/healthy level of function. Symptom scales: 0 = lowest level of symptomatology and 100 = highest level of symptomatology.
b SF-36 scores range from 0–100, with 0 = lowest possible health status and 100 = best possible health status.
cWithin normal ranges for same age group.

Studies of risk-reducing surgery for FAP have found that general measures of quality of life have been within normal range, and the majority reported no negative impact on their body image. However, these studies suggest that risk-reducing surgery for FAP may have negative quality-of-life effects for at least some proportion of those affected.

Chemoprevention

Chemoprevention trials are currently under way to evaluate the effectiveness of various therapies for persons at risk of LS and FAP.[64,65] In a sample of persons diagnosed with FAP who were invited to take part in a 5-year trial to evaluate the effects of vitamins and fiber on the development of adenomatous polyps, 55% agreed to participate.[66] Participants were more likely to be younger, to have been more recently diagnosed with FAP, and to live farther from the trial center, but did not differ from nonparticipants on any other psychosocial variables.

Family communication

Family communication about genetic testing for hereditary CRC susceptibility, and specifically about the results of such testing, is complex. It is generally accepted that communication about genetic risk information within families is largely the responsibility of family members themselves. A few studies have examined communication patterns in families who had been offered LS genetic counseling and testing. Studies have focused on whether individuals disclosed information about LS genetic testing to their family members, to whom they disclosed this information, and family-based characteristics or issues that might facilitate or inhibit such communication. These studies examined communication and disclosure processes in families after notification by health care professionals about a LS predisposition and have comprised relatively small samples.

Research findings indicate that persons generally are willing to share information about the presence of a LS-predisposing mutation within their families.[67-70] Motivations for sharing genetic risk information include a desire to increase family awareness about personal risk, health promotion options and predictive genetic testing, a desire for emotional support, and a perceived moral obligation and responsibility to help others in the family.[68-70] Findings across studies suggest that most study participants believed that LS genetic risk information is shared openly within families; however, such communication is more likely to occur with first-degree relatives (e.g., siblings, children) than with more distant relatives.[67-70]

One Finnish study recruited parents aged 40 years or older and known to carry an MMR mutation to complete a questionnaire that investigated how parents shared knowledge of genetic risk with their adult and minor offspring. The study also identified challenges in the communication process.[71] Of 248 parents, 87% reported that they had disclosed results to their children. Reasons for nondisclosure were consistent with previous studies (young age of offspring, socially distant relationships, or feelings of difficulty in discussing the topic).[68,69,72] Nearly all parents had informed their adult offspring about their genetic risk and the possibility of genetic testing, but nearly one-third were unsure of how their offspring had used the information. Parents identified discussing their children’s cancer risk as the most difficult aspect of the communication process. Of the 191 firstborn children informed, 69% had undergone genetic testing. One-third of the parents suggested that health professionals should be involved in disclosure of the information and that a family appointment at the genetics clinic should be made at the time of disclosure.

In regard to informing second- and third-degree relatives, individuals may favor a cascade approach; for example, it is assumed that once a relative is given information about the family’s risk of LS, he or she would then be responsible for informing his or her first-degree relatives.[67-69] This cascade approach to communication is distinctly preferred in regard to informing relatives’ offspring, particularly those of minor age, and the consensus suggests that it would be inappropriate to disclose such information to a second-degree or third-degree relative without first proceeding through the family relational hierarchy.[67-69,72] In one study, persons who had undergone testing and were found to carry a LS-predisposing mutation were more likely than persons who had received true negative or uninformative results to inform at least one second-degree or third-degree relative about their genetic test results.[70]

While communication about genetic risk is generally viewed as an open process, some communication barriers were reported across studies. Reasons for not informing a relative included lack of a close relationship and lack of contact with the individual; in fact, emotional, rather than relational, closeness seemed to be a more important determinant of the degree of risk communication. A desire to not worry relatives with information about test results and the perception that relatives would not understand the meaning of this information also have been cited as communication barriers.[70] Disclosure seemed less likely if at-risk individuals were considered too young to receive the information (i.e., children), if information about the hereditary cancer risk had previously created conflict in the family,[69] or if it was assumed that relatives would be uninterested in information about testing.[68] Prior existence of conflict seemed to inhibit discussions about hereditary cancer risk, particularly if such discussions involved disclosure of bad news.[69]

For most participants in these studies, the news that the pattern of cancers in their families was attributable to a LS-predisposing mutation did not come as a surprise,[67,68] as individuals had suspected a hereditary cause for the familial cancers or had prior family discussions about cancer. Identification of a LS-predisposing mutation in the family was considered a private matter but not necessarily a secret,[67] and many individuals had discussed the family’s mutation status with someone outside of the family. Knowledge about the detection of a LS-predisposing mutation in the family was not viewed as stigmatizing, though individuals expressed concern about the potential impact of this information on insurance discrimination.[67] Also, while there may be a willingness to disclose information about the presence of a mutation in the family, one study suggests a tendency to remain more private about the disclosure of individual results, distinguishing personal results from familial risk information.[72] In a few cases, individuals reported that their relatives expressed anger, shock, or other negative emotional reactions after receiving news about the family’s LS risk;[69] however, most indicated little to no difficulty in informing their relatives.[68] It was suggested that families who are more comfortable and open with cancer-related discussions may be more receptive and accepting of news about genetic risk.[69]

In some cases, probands reported feeling particularly obliged to inform family members about a hereditary cancer risk [69] and were often the strongest advocates for encouraging their family members to undergo genetic counseling and testing for the family mutation.[67] Some gender and family role differences also emerged in regard to the dissemination of hereditary cancer risk information. One study reported that female probands were more comfortable discussing genetic information than were male probands and that male probands showed a greater need for professional support during the family communication process.[68] Another study suggested that mothers may be particularly influential members of the family network in regard to communicating health risk information.[73] Mutation-negative individuals, persons who chose not to be tested, and spouses of at-risk persons reported not feeling as personally involved with the risk communication process compared with probands and other at-risk persons who had undergone genetic testing.[67]

Various modes of communication (e.g., in-person, telephone, or written contact) may typically be used to disclose genetic risk information within families.[67-69] In one study, communication aids such as a genetic counseling summary letter or LS booklet were viewed as helpful adjuncts to the communication process but were not considered central or necessary to its success.[68] Studies have suggested that recommendations by health care providers to inform relatives about hereditary cancer risk may encourage communication about LS [69] and that support by health care professionals may be helpful in overcoming barriers to communicating such information to family members.[72]

Much of the literature to date on family communication has focused on disclosure of test results; however, other elements of family communication are currently being explored. One study evaluated the role of older family members in providing various types of support (e.g., instrumental, emotional, crisis help, and dependability when needed) among individuals with LS and their family members (206 respondents from 33 families).[7,74] Respondents completed interviews about their family social network (biological and non-biological relatives and others outside the family) and patterns of communication within their family. The average age of the respondents and the members of their family social network did not differ (~ age 43 years). The study found that 23% of the members of the family social network encouraged CRC screening (other types of support, such as social support, were reported much more frequently). Those who encouraged screening were older, female, and significant others or biological family members, rather than nonfamily members. Given that many of the members of the family social network did not live in the same household, the study points out the importance of extended family in the context of screening encouragement and support.

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