Familial Cancer

, Volume 12, Issue 2, pp 325–339

100 years lynch syndrome: what have we learned about psychosocial issues?

Authors

    • Division of Psychosocial Research and Epidemiology and Family Cancer ClinicThe Netherlands Cancer Institute
  • Mary Jane Esplen
    • University Health Network, Faculty of MedicineUniversity of Toronto
  • Bettina Meiser
    • Prince of Wales Clinical SchoolUniversity of New South Wales
  • Helle Vendel Petersen
    • Clinical Research Center, HNPCC RegisterCopenhagen University Hospital, Hvidovre
  • Andrea Farkas Patenaude
    • Dana-Farber Cancer InstituteHarvard Medical School
Original Article

DOI: 10.1007/s10689-013-9653-8

Cite this article as:
Bleiker, E.M.A., Esplen, M.J., Meiser, B. et al. Familial Cancer (2013) 12: 325. doi:10.1007/s10689-013-9653-8

Abstract

In the care of patients with Lynch Syndrome (LS), a range of psychosocial issues are encountered, which significantly affect patient outcomes. A brief historical background of ‘psycho-onco-genetics’ (the domain where psychology, oncology and genetics meet) in relation to LS is presented, followed by an overview of important psychosocial issues identified in the past 20 years. The identification of mismatch repair genes in 1993–1994 made possible genetic counseling and testing for patients who had cancer and for potentially high-risk relatives without cancer. At that time, concerns were raised about the potentially negative psychosocial impact of predictive genetic testing. Since 1993, a large number of studies have been conducted to investigate the possible psychosocial benefits and limitations of such testing. This article presents an overview of: the uptake of and motivations for genetic testing, its psychosocial impact (e.g. psychological adaptation, impact on risk perception and self-concept, and concerns about, and experiences of, genetic discrimination), psychological screening instruments, adherence to and decision-making about preventive strategies, family communication, lifestyle changes, reproductive technology utilization, and professional psychosocial support needs of members of families with LS. Finally, challenges for the future are discussed, including population screening and genomic testing.

Keywords

PsychosocialLynch SyndromeOverviewImpact of genetic counseling and testing

Introduction

Lynch Syndrome (LS), formerly known as hereditary non-polyposis colorectal cancer or HNPCC, is thought to be the most common hereditary colorectal cancer syndrome. LS probably accounts for 1–3 % of all colorectal cancers [1]. This autosomal dominantly inherited disorder is caused by a defect in one of the mismatch repair (MMR) genes [2]. LS is characterized by a high risk of developing colorectal cancer (25–75 %) and endometrial cancer (30–70 %) [1], and a smaller, but increased, risk of developing other tumors, such as small bowel cancer in men, breast cancer in women, and urothelial cancer in MHS2 mutation carriers [3]. Development of tumors occurs at a relatively young age (mean age is approximately 45 years) [4]. Effective screening and early detection techniques for colorectal premalignant adenomas are available, and thus the potential benefits of genetic counseling and testing in terms of reducing morbidity and mortality are potentially substantial [57]. At the same time, informing individuals about their increased genetic risk of colorectal cancer raises a number of important psychosocial issues.

Historical perspective of psycho-oncology and Lynch Syndrome

Cancer, although considered a modern Western disease, is as old as mankind. Until the first half of the 20th century, however, the diagnosis of cancer was, in most cases, a death sentence. To prevent emotional burden and stigma, a cancer diagnosis was frequently not communicated to the patient. As a result of the improvements in cancer treatments in the 1950s and 1960s, and because of the ethical imperative for patients to give informed consent for treatment and research participation, shifts towards more open communication with cancer patients occurred [8]. As a consequence, psychology and psychiatry entered the field of oncology and papers on psychological reactions to cancer appeared. For example, Sutherland and his group reported on the psychosocial consequences of cancer, including the responses to colostomy [9]. Questionnaires assessing ‘quality of life’ were developed in the 1980s and 1990s to measure physical, social, and emotional wellbeing [10, 11] and quality of life outcome measures became standard in cancer clinical trials investigating the effect of new anti-cancer agents. By the twenty-first century, the screening of distress (‘the 6th vital sign’) in cancer patients and those at high risk of developing cancer has been advocated and implemented as a routine part of cancer care [12].

Parallel to developments in cancer treatment and psycho-oncology, the field of genetics emerged. The hypothesis that diseases like colorectal cancer and gynaecological cancer could be inherited was reported for the first time in 1913 Warthin [13]. In the 1960s, the first papers on genetic counseling for cancer appeared. Lynch [14] was among the pioneers to describe the importance of genetic counseling for persons from a so-called ‘cancer family’. Krush et al. [15] reported that fear of a cancer diagnosis appeared to be particularly prevalent and intensified in members of families with multiple members with cancer. A major objective in counseling patients with hereditary cancer was determined to be alleviation of the patient’s fears and anxieties [17] and to reach that objective, “the physician must be willing to take the time to listen to the patient and encourage him to discuss openly his feelings, attitudes and fears about cancer. This may prove to be therapeutic to the patient”. Although not labeled as such, the importance of psychosocial issues in counseling families with LS was already recognized.

A current literature search on “oncogenetic counseling and related issues” reveals over 10,000 papers published since 1967, with a strong increase in the 1990s, when a number of genes associated with cancer syndromes, including those associated with LS, were identified. In this period, again, concerns were raised about the potential psychological harm of genetic testing but also about the need to emphasize preventive strategies for cancer [16, 17]. After 20 years experience with genetic counseling and testing for LS, a number of critical psycho-social issues have been identified and studied. A selection of the most important findings is presented in the following sections.

Uptake of genetic testing and motivations

Uptake of genetic testing for LS via clinical genetic centers

Genetic counseling and testing for LS is thought to be beneficial for carriers as well as non-carriers. Mutation carriers are offered a surveillance program. Periodic colonoscopy is an effective means of reducing the incidence and mortality of colorectal cancer in individuals with a family history of this disease [18]. Colonoscopies are recommended every 1–2 years starting from age 20–25 [1921]. In addition, women from families with LS are also recommended to undergo gynaecological surveillance annually. Large-scale surveillance programs for families with LS, using early detection techniques (e.g. colonoscopy) for colorectal premalignant adenomas have shown a 62 % reduction in the incidence of colorectal cancer and a 65–70 % decrease in mortality [22, 23]. It is, therefore, of great importance that LS carriers comply with screening advice. Non-carriers, who are at general population risk, can be released from this burdensome surveillance program. Learning their relatively low risk of developing LS-associated cancers can be a relief, not only for themselves, but also for their offspring. Despite these benefits, not all high-risk individuals want to know their genetic risk status. The uptake rates of genetic testing for LS vary widely between 14 and 75 % of those offered testing [2429]. This large variation may reflect differences in culture and sample selection bias [30], but also a change over time, since genetic testing is now more commonplace in Western societies then it was in 1993/1994, when the first MMR genes were identified.

Motivation for (not) requesting genetic testing for LS

It is important for clinical geneticists and genetic counselors to be aware of the motives and informational needs of counselees in order to provide optimal, tailored counseling and advice [31, 32]. Studies, including those of primarily individuals without cancer, have reported that ‘early detection of cancer’, ‘knowledge of one’s children’s’ risk’, ‘reduction of uncertainty’, and ‘information on whether (continued) screening is necessary’ are the primary reasons for undergoing genetic testing for LS [25, 33, 34]. Some couples may also use the genetic information to make reproductive decisions [35]. Among colorectal cancer survivors, motivations for genetic testing were comparable to those of clinic-based samples, and included ‘learning of the increased risk of offspring’, and ‘finding out if additional screening was needed’ [36].

Most frequently stated reasons for declining or early withdrawal from genetic counseling for cancer are: concerns about health insurance (41 %), cost of genetic counseling and testing (32 %), potentially adverse emotional impacts of the process on oneself or one’s family (30 %), low anticipated benefit (30 %), and time commitment (24 %) [37]. Other studies conducted in the U. S. confirm that concern about discrimination by health insurers plays a particularly important role in non-participation in genetic testing [25], despite the fact that such fear is reported to greatly exceed actual discrimination practices [38].

Uptake of genetic testing via CRC population screening

Since probably only a small minority of the families with LS has been identified, there is discussion about the optimal strategies to identify individuals at high risk for colorectal cancer [39, 40]. A survey among 14 Western European countries showed that the main strategy to identify families at risk for LS, in all countries, was by obtaining a family history followed by referral to clinical genetic centers of suspected cases [41]. However, since the awareness of the general population about familial colorectal cancer is limited, and the quality of the family histories taken by general practitioners and hospitals is reported to often be poor [41], other strategies of identifying high risk families are now being considered. Immunohistochemical (IHC) analysis or MSI-analysis of a colorectal tumor could be offered to all newly diagnosed patients with colorectal or endometrial cancer, regardless their family history [39, 41], or to patients who meet the revised Bethesda Guidelines for LS [42, 43]. Psychological impact of such testing might be expected to differ from that of genetic testing in individuals with a family history of cancers associated with LS, since the cohort of newly diagnosed patients as a whole is likely to have had less prior family experience with colorectal and related cancers, making a diagnosis of LS potentially more distressing.

How psychologically burdensome is genetic testing for newly diagnosed patients? Besides coping with their own diagnosis and discomfort due to the treatment, providing genetic information means that patients will also have to cope with the information that their children and other close relatives are at increased risk for developing cancer, and that they themselves are at life-long increased risk for developing other cancers. In a study on attitudes of patients meeting the revised Betheseda criteria for LS, it was found that participants held positive attitudes about the potential benefits of the microsatellite instability (MSI) testing done at diagnosis, and perceived few barriers to undergoing testing [44]. Landsbergen et al. [45, 46] studied the psychological effects of discussing genetic testing and referring patients during treatment. In these patients, three themes were found. They experienced genetic testing during treatment as: ‘a change in life after the diagnosis of colorectal cancer’, ‘a warning for the future’, and as ‘important in the communication with family’. Although coping with the physical and psychosocial consequences of colorectal cancer was experienced as a considerable challenge, the advantages of undergoing genetic testing to clarify one’s risk and thus enable tailored implementation of preventative strategies, specifically for children, outweighed disadvantages. To facilitate informed decisions regarding MSI-analyses, Manne et al. [47] developed a CD-ROM decision aid for patients with suspected LS. Those who used the decision aid reported increased knowledge about MSI tests, greater preparedness to make testing decisions, lower decisional conflict and greater decisional self-efficacy. It was concluded that education strategies, such as CD-ROM decision aids may be valuable components in informed consent for individuals at risk for LS who are offered MSI testing [47, 48].

Psychosocial impact of genetic counseling and testing for LS

Prevalence of distress and risk factors

Studies have reported that 6–30 % of individuals receiving genetic counseling for colorectal cancer have clinically relevant levels of distress (e.g. anxiety or depression) or serious cancer-specific worries pre- or post-genetic testing [4954]. Potential risk factors for psychological distress in individuals undergoing genetic counseling for cancer include: being female [52], education (with conflicting findings about the direction of the association) [52, 55], high cancer risk perception [55], being the first in the family to undergo genetic counseling/testing [56], high levels of distress prior to counseling [50, 57], a history of major or minor depression [58], the experience of parental cancer during childhood [59], lack of social support [50, 52], and having received professional psychosocial support/therapy in the past [49].

Psychological adjustment to genetic testing for LS

Several prospective studies have assessed psychological adjustment to genetic testing for LS and assessed the impact of testing in people at increased risk for LS [33, 50, 58, 6068].

Most of these studies assessed the psychological impact of genetic testing for LS in individuals without a personal history of the cancer types associated with LS (hereafter they are referred to as ‘unaffected’ individuals) [33, 50, 58, 6068]. Unaffected non-carriers experience psychological benefits from genetic testing, with both short- and long-term decreases in colon cancer anxiety [63, 64, 68]; some studies also report decreases in generalized anxiety [33, 63, 64] and depression [63, 64]. Among unaffected carriers, studies report either no change in psychological distress or only short-term increases in cancer-specific anxiety, generalized anxiety or depression [33, 63, 68, 69]. Studies also indicate no adverse long-term effects of testing among unaffected carriers. In summary, findings from prospective studies examining the psychological impact of genetic testing for LS show a clear psychological benefit of testing for unaffected non-carriers and an absence of long-term increases in distress among unaffected carriers.

Very little is known about the psychological impact of genetic testing for LS among those who have been affected with cancer who received either positive or uninformative results. Very few studies included people affected with cancer [50, 58, 67]. One study found no changes in distress levels over time [50], while another study, which followed up affected and unaffected people at risk for LS, found all individuals who underwent testing and were subsequently diagnosed with depression were affected with colorectal cancer [58]. In this study, the only predictor of psychological distress was a history of major or minor depression. These preliminary results suggest that affected people may be more vulnerable and that genetic testing may amplify their former cancer experience.

Risk perception

During genetic counselling, patients are presented with substantial, complex information, which provides the basis for informed decisions related to genetic testing and surveillance [70]. This information includes estimates of the risks of developing cancer and carrying a predisposing mutation [71]. Risk is difficult to quantify accurately by individuals [72] and is not easily understood [73, 74]. There is evidence that different individuals interpret risk estimates differently, and it is thus difficult to know how an individual comprehends the concept of risk [75].

Mutation carriers’ perceived risks have been shown to differ from risk estimates communicated during genetic counselling [76, 77]. Perception of risk is influenced by familial beliefs about risk, personal experiences and communication within the family [78, 79]. Risk perception is embedded within personal theories where the familial context (i.e. the families’ experiences and history of cancer) is a key feature of how risk is perceived and utilized, rather than being simply experienced as rational in nature or as medical facts [78, 80, 81]. It is important to notice that risk perception is not only related to one’s personal risk, but also to risks in the extended family [78, 80]. Understanding the way risk perception is shaped within a family is helpful to guide how risk information should be provided [78].

It is the perception of an event rather than the event itself that determines cognitive, emotional and behavioral consequences [82]. It has been reported that many carriers of mutations associated with LS, despite a strong family history of cancer, feel optimistic about their future due to early detection and prevention options being available [78, 83]. Prevention and surveillance programmes offer mutation carriers the opportunity to reduce their risk and/or detect cancer early [79], and may thus alter the perception of risk. It is unclear, going forward, how risk perception of new generations of families with LS may be influenced by the cancer incidence reduction through surveillance and risk-reducing surgery.

Self-concept

Most studies on psychosocial impacts of genetic testing have utilized global measures of psychological functioning, such as those measuring symptoms of anxiety or depression. Recent research has incorporated newly developed measures to address specific impacts of genetic testing, such as the impact on self-concept [84, 85]. Self-concept is a complex cognitive construct related to how we think about and evaluate ourselves in relation to the surrounding society and through our experiences [86, 87]. Any new information about the self, including that of genetic knowledge, can be a threat to an existing self-concept [88]. The literature, in fact, describes the notion of a ‘genetic self’ [89] and Schild [90] has referred to a ‘genetic identity’.

As noted above, while the majority of individuals appear to adapt to new genetic information, individuals who carry mutations for LS have reported feelings of stigma and feeling “different than others” and often describe a sense of heightened vulnerability around their health [85]. This is particularly the case for females and those with less education [91]. Individuals with mutations associated with LS often experienced prior losses in the family and are very aware of the potential risks for developing tumors. Quality of life impacts, such as body image alterations, perceptions of health risks and impact on personal relationships have been documented [92]. Individuals who carry mutations may also have specific bowel-function-related worry or embarrassment, along with the felt need to frequently monitor their bowel function and are more likely to feel anxious as a result [85]. Other specific self–concept impacts include a sense of guilt related to the possibility of passing a genetic mutation to one’s children, despite an understanding that this factor is out of one’s control [85].

Self-concept involves not only a sense of one’s current self but also incorporates future-oriented representations or possible selves [88]. While some individuals report feeling vulnerable and worried about their futures, other individuals who carry mutations associated with LS report feeling hopeful about themselves in the future and able to deal well with a genetic test result [85]. Such optimism is likely due to the availability of effective surveillance options, which lead to early detection and thus improved treatments of colorectal cancer.

Impacts on self-concept vary. Generally, it is believed that individuals with a more positive perception of the self are more apt to endure threat, loss and misfortune compared to individuals with a more negative self-concept [88, 93]. Culture may also play a role in this variation. For example, one study found carriers in Denmark and Sweden had fewer negative self-concept impacts in relation to the guilt of passing on a genetic mutation or the potential loss of privacy, compared to a Canadian sample of carriers with LS related mutations [91], while Danes exhibited greater cancer worries [91]. How a person views him/herself may influence motivation to adopt screening or health-protective behaviors [88]. Future work is needed to assess specific self-concept impacts and their relationship to variables such as adherence to surveillance and other health behaviors.

Genetic discrimination

Besides concerns about the possible negative emotional impact of genetic counseling, concerns have also been raised about the possible impact of genetic knowledge on obtaining life insurance, a mortgage or employment [94]. Some counselees worry that personal information about the results of genetic testing may be required by insurance companies, and that this may result in limited coverage, increased costs, or denial of insurance [95]. In a US study among unaffected individuals with a family history of colorectal cancer, approximately half rated their level of concern about genetic discrimination as high. Those with higher levels of concern felt they would be more likely to pay for testing out of pocket, use an alias, or ask for test results to be excluded from their medical record. However, their awareness and understanding of legislation regarding genetic discrimination was found to be minimal [96]. In a Finnish study, no differences were found between carriers and non-carriers in life or health insurance coverage within 12 months after genetic counseling and testing for LS [97]. In a Dutch study, on average 4 years after genetic counseling for LS, 8 % of counseled individuals reported problems in obtaining a life insurance, 2 % problems in obtaining a mortgage, and 2 % problems in the choice or change of jobs [98]. Also, in an Australian study, some cases of genetic discrimination have been reported [99]. In a recent systematic review on genetic discrimination and life insurance for various genetic disorders, including LS, it was concluded that individual cases of genetic discrimination do exist [100]. However, due to methodological limitations of the studies, no conclusion can yet be made about the (low) prevalence or the impact of discriminatory practices [100].

Need for psychological screening

It is encouraging that the majority of individuals benefit from genetic counseling and adapt to genetic information. However, consistent evidence identifies an important subgroup that continues to experience distress levels, which warrant psychological intervention. As noted above, risk factors for psychological distress among individuals undergoing genetic testing have been identified.

For those individuals who have more difficulty coping with their risk or genetic knowledge, associated emotional reactions may impede the assimilation of information and the adoption of preventive measures [101, 102]. Knowledge of factors associated with poor adjustment has contributed to the development of instruments to identify individuals at increased psychological risk.

While the gold standard for identifying psychologically distressed individuals involves structured clinical interviews administered by a clinical psychologist or psychiatrist [103], such an approach is costly and often not feasible in genetic clinics. Standardized measures of psychological functioning (e.g. anxiety, depression) can also be used to identify distress; however, few clinics use these measures in practice because of personnel and time requirements for scoring and interpretation. Furthermore, these instruments measure global symptoms that are consistent with the diagnostic classifications of anxiety and/or depression and lack sensitivity to the important and unique issues surrounding genetic testing [103, 104]. To address this area of service, psychological screening instruments have been developed for the genetics context. For example, the multidimensional impact of cancer risk assessment (MICRA) is designed to assess concerns and impacts associated with genetic testing for BRCA1/2 mutations [104] and the Psychological Adaptation to Genetic Information Scale is also available [89]. Two, more recently developed screening tools have been described. One is a psychological risk tool, the “Genetic Psychosocial Risk Instrument”, that incorporates past experiences with the heritable illness, expectations associated with a genetic testing result as well as past psychosocial history. It aims to identify individuals, who may benefit from added psychosocial support [105]. The second cancer genetics-specific screening questionnaire is the ‘Psycho-Oncogenetics (POG) questionnaire’, which is developed to facilitate communication about psychosocial problems, problem management, and to reduce levels of distress in those who apply for genetic counseling for cancer [106, 107]. While these measures will require further validation, they provide more clinically relevant approaches to capturing specific impacts of genetic information, such as the sense of increased vulnerability and continued uncertainty often experienced during and following genetic counseling and testing [89, 104].

Adherence to, and decision-making about, preventive programs

Compliance to surveillance programs

It cannot be assumed that carriers will necessarily adopt appropriate screening behaviors following genetic testing. Several studies have assessed colonoscopy screening behaviors following genetic testing [51, 64, 68, 69, 108]. Such studies are important in order to ascertain whether individuals who undergo genetic testing translate results from such testing into appropriate screening behaviors. Studies among unaffected carriers following genetic testing found that between 53 and 100 % adhered to recommendations for colonoscopy screening, while only a minority (7–16 %) of non-carriers had colonoscopy screening [51, 64, 68, 69, 108]. In a Dutch study among individuals from families with LS, it was found that non-compliance was rare. However, significant delays of more than 1 year in undergoing screening were observed in 25 % of the cases [51]. Comparable results were found in a recent Finnish study among LS mutation carriers, with 83 % reporting being fully compliant and 17 % reporting a delay between two colonoscopies [68]. In both studies, general anxiety or cancer worry was not associated with surveillance behavior. However, the number of perceived barriers to screening (including discomfort and embarrassment) was associated with screening delay. Stoffel et al. [109] also reported that one important reason for missing colonoscopic examinations was worrying about discomfort of the test. Therefore, the use of sedatives is recommended, since it may facilitate better compliance [51].

Most non-carriers are pleased that colonoscopies are no longer necessary [54]. However, one third report some concerns about stopping surveillance [54]. Non-carriers who had post-test colonoscopy are also more likely to report doubts about test validity compared to carriers [68].

Earlier studies reported that adherence to gynecological screening recommendations is lower than to those regarding colonoscopy screening. Women with LS have been found to be less aware of their increased risk for extracolonic cancers and to be less likely to undergo endometrial cancer screening compared to colonoscopy screening before genetic counseling [110]. A recent study, including 471 women from families with LS, suggested that awareness of endometrial cancer was the most important predictor of compliance with gynecological screening. However, a substantial number of women (35 %) were not aware of their increased risk [111]. Therefore, it is of great importance to increase awareness among high-risk women about the risk of extracolonic cancers and screening options. In contrast, a recent study reported high compliance rates of 97 %, suggesting high awareness in this Finnish registry cohort [112].

Decision-making about preventative surgery and chemoprevention

Preventive colectomy is not routinely recommended for those carrying a mutation but may be discussed as an option, depending on individual circumstances. For women carrying a mutation, risk-reducing hysterectomy and salpingo-oophorectomy might also be considered after the age of 30–35 years or when childbearing is complete [113]. With respect to gynecological cancers, data are available that demonstrate the efficacy of risk-reducing surgery in reducing the occurrence of endometrial and ovarian cancers [113].

Almost no data are available that document uptake of risk-reducing surgery in people at risk for LS. In one of the few studies available, Collins et al. [64] reported data on 19 carriers, who had been followed up for 3 years following testing; none of the carriers reported having had a risk-reducing colectomy since receiving their genetic test result and only two women reported having had a risk-reducing oophorectomy. The most likely reason for lack of uptake of colectomy is the demonstrated efficacy of colonoscopy screening, such that surgery may not be considered necessary to prevent colorectal cancer. However, given the demonstrated efficacy of risk-reducing surgery in preventing the occurrence of endometrial and ovarian cancers [113], more studies are needed to document uptake of such surgery, how women make decisions about surgery and the psychological impact of surgery. A recent study among women undergoing genetic testing for LS found that 20 % of women would consider having children earlier in order to have risk-reducing surgery to reduce their risk for gynecologic cancers [35]. Prospective studies are needed to ascertain the extent to which attitudes translate into uptake of such surgery.

Data are also accumulating that risk-reducing medication (in particular aspirin) may substantially reduce cancer incidence. Specifically, the international CAPP2 (Colorectal Adenoma/carcinoma Prevention Programme) RCT has demonstrated that 600 mg aspirin per day for a mean of 25 months substantially reduces cancer incidence [114]. While the results from an ongoing dose-finding study in people with LS will not be available for several years, data on attitudes to risk-reducing medication to reduce colorectal cancer risk in individuals at increased genetic risk are urgently needed to document current uptake of, and perceived barriers to taking aspirin and to inform the development of interventions to support uptake.

Family communication in families with Lynch Syndrome

Communication between an informed, tested member of a family with LS and other relatives is the critical link in getting relatives to attend for genetic counseling and testing and, when appropriate, to initiate recommended cancer screening at appropriate ages [80, 115]. Without success in these efforts, needless deaths will continue to occur despite our knowledge of the genetic etiology of LS-associated cancers.

Considerable international study of the pattern of communication within LS family members reveals that the telling of adult, first-degree relatives (FDRs) is quite widespread, although not all FDRs are told [29, 116]. Communication to second-degree relatives is considerably less complete [115]. Reasons offered for not communicating with adult relatives include perception of the recipient as lacking sufficient maturity [29], estrangement and family disruption [80, 117] and hesitancy in conveying potentially painful information, i.e. to keep others from “feeling the same sorrow” [29, 115, 118]. Also mentioned were parents’ difficulties understanding complex genetic and medical information about LS; indeed misconceptions about hereditability are not uncommon among tested individuals [80]. If a first attempt at family communication is thwarted, telling becomes much less likely [117]. Encouragement from professionals may help encourage the informing of relatives. Also, in families where there have been fatal cases of cancer attributable to LS, motivation for sharing test results was higher [117]. Telling of minor children may be delayed because of the lack of need for immediate medical action and because of concerns about the children’s understanding and maturity to integrate complex information about LS. Families in which cancer occurred at younger ages tended to inform children at younger ages [80]. However, parents often find it difficult to talk to children, including adult children, about the children’s cancer risks [29]. A recent study showed 13 % of mutation carriers in Finland did not tell their children their test result.

Those reported to be more likely to adopt the role of family communication disseminator include those with positive test results [80], older family members [29, 62] and those with higher scores on measures of existential well-being [119]. While women are often seen as the “kin-keepers” [120] in hereditary cancer families [78, 121], men in families with LS appear more willing to service this role than in breast/ovarian cancer syndrome families [115], perhaps because of the more even gender distribution of cancers in LS. After initial disclosure, family communication tends to diminish, spurred intermittently by surveillance screenings or by encounters with new relatives [80].

Sixty-nine percent of informed firstborn adult children in a recent study proceeded to genetic testing [29]; children of female mutation carriers were nearly three times more likely to undergo genetic testing than children of male carriers. In some families, children did not appear to know what steps to take or were not yet ready to undergo genetic testing following parental disclosure [29]. Family communication and encouragement from family members is positively associated with colonoscopy adherence [122]. While lower socioeconomic status may correlate with greater barriers to screening, familial cultural barriers or strengths appear to have a greater impact on adoption of screening practices [78].

Overall, as has been shown to be the case in other hereditary cancers [116], the strength of psychological factors in family communication about LS is considerable and speaks to the need for genetics professionals to address emotional barriers with sufficient depth when counseling patients about informing at-risk relatives.

Lifestyle changes

Several modifiable life style factors, including smoking, alcohol and diet, affect the risk of developing sporadic colorectal cancer [123]. Whether this applies to LS to the same extent is unclear. Data regarding this issue is growing. Today there is ample evidence that smoking, higher body mass index and a Western diet are associated with higher risk of developing colorectal neoplasia. Fibre intake may be related to decreased risk [1, 124]. Knowledge of people’s dietary beliefs and behavior may be important and are often associated with cancer prevention behaviors, such as participation in surveillance programmes [125].

Research on how individuals at increased risk for hereditary cancer view lifestyle behaviors is limited. Women at risk of hereditary breast cancer are seeking personal control through being proactive, mainly through acquisition of knowledge. However, their behavioral choices are not solely based on knowledge but also on emotional factors, which may lead to unhealthy lifestyle choices [126]. Some studies have reported associations between having a family history of cancer and life style behaviors [127, 128], while others have not found such associations [129].

A recent quantitative study, based on 390 individuals from families at risk for LS-related cancers, suggests that the majority of individuals from families with LS endorse a role of diet in cancer prevention [130]. A qualitative study showed that while some at-risk individuals did not believe cancer to be preventable through lifestyle behaviors, others did and had personal theories of how certain diets were causing cancer in family members [78].

A study evaluating health and lifestyle among persons at risk of hereditary colorectal cancer showed that a colorectal cancer diagnosis might improve lifestyle behaviors. Unaffected individuals reported lifestyle behaviors comparable to the general population, suggesting that unaffected individuals may benefit from changes in lifestyle behaviors [131]. Recommendations for cancer prevention for individuals from families with LS should include smoking abstinence and maintenance of a normal weight range [1].

Reproductive technology utilization and acceptance among individuals in families affected by Lynch Syndrome

Reproductive technologies offering pre-natal diagnosis (PND) or pre-implantation genetic diagnosis (PGD) have been available for several decades [132]. These methods have been applied to prevention of births of children with cancer predisposition syndromes that have early ages of onset, i.e. Li-Fraumeni Syndrome [133], Familial Adenomatous Polyposis [134], retinoblastoma [135], Multiple Endocrine Neoplasia2 [136], and von Hippel-Lindau Syndrome [137]. More recently, PGD has been advocated for consideration by members of families affected by adult-onset, high-risk cancer predisposition syndromes, i.e. hereditary breast/ovarian cancer and families with LS [138, 139].

Parents who carry deleterious hereditary cancer mutations show high levels of concern about their offspring’s cancer risks and future health [140]. Such worries are often important motivations, leading high-risk individuals to seek genetic counseling and testing. There has been some debate about whether it is ethical to utilize technology to prevent the birth of children who are at risk only for adult-onset cancers which are not uniformly fatal [141]. Professional organizations have suggested that the use of such technologies might be ill advised and could lead to a slippery slope of sex selection [138], though public acceptance of PGD for hereditary cancer risk suggests the public may not equate these options [142, 143].

There are now data showing high rates of hypothetical acceptance of PND and PGD among individuals from families with LS [35]. However, there is very limited report of uptake of reproductive technologies by LS family members planning pregnancies. There is one report of double-factor PGD, a new approach designed to not only eliminate embryos carrying the deleterious cancer-disposing mutation but also to screen out chromosomal aberrations, hopefully leading to higher rates of implantation and full-term pregnancy [144]. In the reported case, PGD led to the successful birth of twins without the deleterious mutation. A study from Manchester, UK showed that among 98 individuals who are members of an LS registry, one individual planning a pregnancy had indicated interest in using PGD, but none had actually done so. Data from 57 European centers in the European Society of Human Reproduction and Endocrinology (ESHRE) PGD consortium showed only 2 cycles of PGD due to risk for LS over a 4-year period [145].

Potential reasons for not utilizing PGD include psychological, practical and ethical considerations. A major factor is lack of awareness about applicable reproductive technologies. In several studies of acceptance of PGD among hereditary cancer family members, 50–60 % of those surveyed had not heard of PGD until the survey [146, 147]. Cost, restriction of services to major medical centers, lack of contact with reproductive specialists and hesitancy among oncologists to bring up PGD [144, 148] as an option have been discussed as other limiting factors [138]. Another potential factor is the negative judgment such a step may imply about the value of a life lived with a cancer-predisposing hereditary syndrome, as has been noted in relation to other hereditary cancer syndromes [149]. Also, personal and familial cancer experience may color such decisions; as more individuals from families with LS survive due to increased screening and risk-reducing surgery, the impetus to utilize reproductive technologies to prevent passing on the mutation may diminish.

Support needs of members of families with Lynch Syndrome

Information is a critical need for members of families with LS. Whether it is genetic information, information about the nature or value of risk-reduction or prevention strategies, or information about the potential use of PGD to prevent the birth of a next generation of high-risk children, genetics professionals are essential to convey the information and to help members of families with LS to evaluate and personalize it [35, 80, 145, 149]. Research has shown that discussions with physicians, especially those that involve more individualized discussion of patient health beliefs or risk perceptions, are highly influential in decisions about genetic testing, screening uptake or consideration of risk-reducing surgeries [117]. Genetic counselors also play significant roles in the lives of these families. They often, for example, initiate discussions of reproductive planning and help family members with important discussions about the challenge of family communication [150]. Many genetic counselors serve ongoing needs for informing multiple generations of a family with LS, despite health system organizations which define genetic counseling as a brief consultative service and have not yet recognized the lifelong needs for genetic counseling in hereditary cancer families.

Distress among members of families with LS has been widely noted, though not typically at levels associated with psychiatric diagnoses. Studies have repeatedly called for more routine availability of psychological services for members of families coping with the complexity of issues, which familial and individual diagnosis of LS can precipitate [46, 151, 152]. Serving the needs of this increasing cohort of families with LS and other families with hereditary cancer may necessitate training a larger cohort of mental health professionals to work in cancer genetic clinics.

Challenges for the future

Cancer genetic counseling is evolving and there are some important new developments that require careful consideration. First, it is expected that the number of sessions with the genetic counselor may be reduced from three visits (which is the proposed number of visits according to most guidelines) to one visit [153]. Indeed data from a small pilot randomized controlled trial (RTC) are available that show that shortened genetic counseling may be an effective means of providing genetic information to individuals at increased risk for LS, but larger RCTs are required before any conclusions can be drawn as to the safety of such abbreviated genetic counseling [154]. There is also the potential for no contact with a genetic counselor emerging through ‘direct-to-consumer’ genetic testing [155]. These recent developments raise some questions, such as how will the associated psychological and social issues discussed above be addressed? Evidence to date suggests benefits of comprehensive genetic counseling approaches and, as noted above, strategies to identify those individuals who require additional support are available that allow for optimized utilization of limited resources. However, if genetic counseling is streamlined, what are the risks? Will this lead to increased potential for misinterpretation of genetic test results? What will be the impacts on the uptake of important surveillance recommendations? How will individuals effectively manage the challenging family communication issues? The trend towards reducing contact with a genetic counselor is in contrast to current developments of ‘personalized medicine’, aiming to provide more personalized, multidisciplinary approaches to care of those at risk for LS [156]. We suggest careful consideration in adopting these recent trends. Genetic testing is life-altering and the failure to effectively manage its potential impacts may potentially lead to harm as well as ultimately miss the opportunity to optimally use new genetic and reproductive technologies. Any proposed alternative ways of providing information and support, e.g. via the internet, should be carefully developed and tested; decisions about utilization should be based on solid evidence of efficacy and patient satisfaction.

Secondly, during the past 20 years, we have learned that perceived risk, rather than actual risk, of developing cancer is associated with health behaviors, such as adhering to a healthy life style and compliance with recommended surveillance [157]. Perceived risk to a large extent is determined by the prior family experience of cancer and other personal attributes, such as coping style, and less so by the genetic or risk information itself. Strategies to support cancer surveillance programs, therefore, need to consider an individual’s perception and understanding of his/her risk in order to successfully motivating the individual to adhere to the recommended follow-up screening.

Thirdly, in the near future, population screening for all colorectal and endometrial cancers may become common practice [158]. MSI/IHC screening tests are typically being undertaken without formal pre-test genetic counseling and informed consent. The recommendation to get tested for LS shortly after a cancer diagnosis may result in additional stress for the patient. Careful preparation and educational support of the patient prior to receiving a genetic test result can assist the patient to cope with an additional diagnosis of LS. Population screening for all colorectal cancer patients will impact not only on prevention strategies but also on treatment decisions [156]. Surveillance and treatment programs may be tailored to the specific mutation, and, if applicable, decision aids, including web-based decision tools, can be useful to support carriers to choose the preventive strategy that best fits their preferences.

Fourthly, genetic testing for single nucleotide polymorphisms (SNPs) related to colorectal cancer risk are now commercially available through direct-to-consumer genetic testing. These gene variants convey a modestly increased risk for developing colorectal cancer only. Studies on patient acceptance of, and psychosocial responses to, genomic testing for colorectal cancer risk have now been undertaken [159161]. The studies found that almost all study participants were willing to opt for testing of SNPs related to colorectal cancer risk. Testing had no impact on quality of life, cancer worry or distress, but led to increased uptake of healthy behaviors, such as healthy eating and exercise. Conflicting results on the willingness to start colorectal cancer screening were reported and need to be studied in larger prospective studies, in which the value of the additional information provided by SNP results should be investigated.

Finally, during the past 20 years, we have gained insights about the psychosocial aspects of genetic testing for LS. However, some groups have received considerable less attention. Cultural minorities have been under-represented in the populations that visit the family cancer clinic, and as a consequence, are underrepresented in psychosocial studies. However, as we move to MSI/IHC screening of all patients, we may be confronted with many more patients with a non-Caucasian background, who may express different levels of interest in being tested for hereditary cancer risk or exhibit specific beliefs or reactions to genetic information [162, 163]. More research into the psychosocial aspects of various cultural minorities, is, therefore, warranted. A second understudied group consists of the new generation of at-risk individuals, who come of age knowing the mutation status of their parent [164]. For parents, there can be considerable decisional conflict about how and when to share genetic information with their offspring [165]. However, once shared, informed young adults will need to make decisions about genetic testing, reproduction, marriage, career, and health behaviors against the background of knowledge of their hereditary disease risks [164]. Future research is needed to obtain insight into their specific needs for information and support and to understand the long term perspective of the “second and third generations” of carriers.

Acknowledgments

We thank Dr. Matthijs Bleiker for his helpful suggestions to improve the content of this paper, Suzanne Bakker and Julia Kornetski for gathering materials needed for the preparation of this manuscript, and Miranda Gerritsma for her help with the references. Bettina Meiser is supported by a Career Development Award from the National Health and Medical Research Council (NHMRC) of Australia.

Copyright information

© Springer Science+Business Media Dordrecht 2013