# Psychosocial and clinical factors of probands impacting intrafamilial disclosure and uptake of genetic testing among families with BRCA1/2 or MMR gene mutations

Nathalie Alegre, Pierre Vande Perre, Yves-Jean Bignon, Aude Michel, Virginie Galibert, Ornellia Mophawe, Carole Corsini, Isabelle Coupier, Jean Chiesa, Laura Robert, et al.

► To cite this version:

Nathalie Alegre, Pierre Vande Perre, Yves-Jean Bignon, Aude Michel, Virginie Galibert, et al. "Psychosocial and clinical factors of probands impacting intrafamilial disclosure and uptake of genetic testing among families with BRCA1/2 or MMR gene mutations." Psycho-Oncology, 2019, 28 (8), pp.1679-1686. 10.1002/pon.5142. hal-02527391

HAL Id: hal-02527391

https://hal.umontpellier.fr/hal-02527391v1

Submitted on 27 Feb 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
PAPER

WILEY

# Psychosocial and clinical factors of probands impacting intrafamilial disclosure and uptake of genetic testing among families with BRCA1/2 or MMR gene mutations

Nathalie Alegre<fnref n="1" /> ID | Pierre Vande Perre<fnref n="1" />,<fnref n="2" /> | Yves Jean Bignon<fnref n="3" /> | Aude Michel<fnref n="4" /> |

Virginie Galibert<fnref n="1" /> | Ornellia Mophawe<fnref n="1" /> | Carole Corsini<fnref n="1" /> | Isabelle Coupier<fnref n="1" /> | Jean Chiesa<fnref n="5" /> |

Laura Robert<fnref n="3" /> | Lydie Bernhard<fnref n="5" /> | Marie-Christine Picot<fnref n="6" />,<fnref n="7" /> | Héléna Bertet<fnref n="6" /> |

Valérie Macioce<fnref n="6" /> | Noëlle Bastide<fnref n="8" /> | Jérôme Solassol<fnref n="1" /> | Jean Marc Rey<fnref n="1" /> |

Frédéric Thomas<fnref n="9" /> | Solange Carton<fnref n="4" /> | Pascal Pujol<fnref n="1" />

**Correspondence**

Professor Pascal Pujol, Mailing address:
Département de Génétique Médicale, service d'Oncogénétique, CHU de Montpellier, Hôpital Arnaud de Villeneuve, 371 avenue du Doyen Gaston Giraud, 34295 Montpellier cedex 5, France.
Email: p-pujol@chu-montpellier.fr

**Funding information**

AstraZeneca, Grant/Award Numbers: 2014-00290 and PRSH11; Ligue Contre le Cancer, Grant/Award Number: PRSH11/99

**Abstract**

**Objective:** Intrafamilial disclosure of hereditary cancer predisposition in BRCA1/2 and mismatch repair gene (MMR) syndromes allows appropriate prevention strategies in at-risk relatives. We previously showed in a nationwide study that the uptake of genetic targeted testing (GTT) in these families was only 30%. We aimed to identify the clinical and psychosocial factors affecting the probands' intrafamilial disclosure and relatives' uptake of GTT in BRCA1/2 or MMR syndromes.

**Methods:** We assessed clinical variables, family history, and psychosocial variables of probands (depressive symptoms, anxiety, alexithymia, optimism, coping, family relationship, perception of cancer risks, and of hereditary transmission), together with disclosure and uptake of GTT within 103 French BRCA1/2 or MMR families.

**Results:** Among relatives eligible for GTT, 68% were informed of the predisposition, and 37% underwent GTT, according to probands' reports. Intrafamilial disclosure was inversely associated with the degree of kinship (P < .01). In multivariable analysis, disclosure increased with time since probands' genetic diagnosis (P < .01) and probands' feeling of family cohesion (0.01). GTT uptake increased with probands' depressive symptoms (0.02) and decreased with probands' perception of cancer risks (0.03). BRCA1/2 and MMR groups did not differ concerning family information and GTT uptake.

**Conclusions:** This study identified factors affecting disclosure to relatives and GTT uptake in BRCA1/2 and MMR syndromes and gives new insights to improve probands' follow-up and intrafamilial sharing of genetic information.

**KEYWORDS**

BRCA1, BRCA2, cancer, disclosure, DNA mismatch repair, family, genes, genetic testing, mutation, oncology

<footnote n="1">¹Unité d'Oncogénétique, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire Montpellier, MIVEGEC, Montpellier, France</footnote>

<footnote n="2">²Université Toulouse III Paul Sabatier, Toulouse, France</footnote>

<footnote n="3">³Laboratoire d'Oncologie moléculaire, CLCC Jean Perrin, Clermont-Ferrand, France</footnote>

<footnote n="4">⁴Département de Psychologie, Université Montpellier III, Montpellier, France</footnote>

<footnote n="5">⁵Département de Génétique médicale et cytogénétique, Centre Hospitalier Universitaire Nîmes, Nîmes, France</footnote>

<footnote n="6">⁶Unité de Recherche Clinique & Epidémiologie, DIM, Centre Hospitalier Universitaire Montpellier, Montpellier, France</footnote>

<footnote n="7">⁷Clinical Investigation Centre, INSERM U1411, Montpellier, France</footnote>

<footnote n="8">⁸Association BRCA France, Montpellier, France</footnote>

<footnote n="9">⁹Centre de Recherches Écologiques et Évolutives sur le Cancer, Montpellier, France</footnote>
# 1 | BACKGROUND

When individuals are tested positive for a pathogenic variant in *BRCA1/2* genes for hereditary breast and ovarian cancer syndrome or in mismatch repair genes (MMR) for Lynch syndrome, their relatives may benefit from genetic targeted testing (GTT). Indeed, personalized screening and prevention strategies reduce cancer risk.¹ We and others previously showed that a proportion of relatives at risk of carrying the familial mutation are not informed of the familial predisposition, and that among those who are informed, not everyone uptakes GTT.²⁻⁶

Different factors may impact intrafamilial disclosure and GTT uptake within families.⁷⁻⁹ Both for *BRCA1/2* and MMR carriers, intrafamilial disclosure and GTT uptake seem more frequent between relatives who are emotionally close or who share a close degree of kinship.¹⁰,¹¹ The proband, the first member of the family who undergoes genetic testing, often feels a moral duty to share genetics results with his relatives and inform them of the availability of GTT.¹²,¹³ This duty is commonly called the "messenger task."¹⁴ In addition to these moral aspects, familial disclosure may also be a legal duty, as in France where it became mandatory in 2013.¹⁵ The key role and the specific vulnerability of the proband have been emphasized in the literature.¹⁴,¹⁶ Often affected by a cancer, he has to cope with his own experience of disease and genetic results, in addition to his complex feelings toward family members. Some studies have explored the impact of different proband's psychosocial characteristics on the dissemination of genetic information, such as worry about cancer or genetic risks,⁴,¹⁰,¹⁷ anxiety,¹⁰,¹⁸ emotional distress,¹⁹⁻²¹ and coping styles.¹⁰,¹⁸ To our knowledge, the impact of the proband's alexithymia, that is the capacity to identify and communicate about one's own emotions, has never been investigated in this specific context.

The aim of our study was to obtain a better insight about psychosocial, sociodemographic, and clinical characteristics of probands associated with intrafamilial disclosure of genetics results and GTT uptake. Our approach included investigation of psychological aspects such as depressive symptoms, anxiety, coping styles, family relationships, perception of cancer risks but also optimism and alexithymia. Characteristics of probands related to intrafamilial disclosure and uptake of GTT were compared between families with *BRCA1/2* and MMR-related syndromes.

# 2 | METHODS

## 2.1 | Study population, design, and setting

This multicenter prospective cohort study was approved by the institutional ethics review board of the University Hospital of Nîmes (#2012.05.01). Every patient included provided written informed consent. Patients were included in the Cancer Genetics Department of the University Hospital of Montpellier, the Medical Genetics and Cytogenetics Department of the University Hospital of Nîmes, and the Centre Jean Perrin of Clermont-Ferrand between August 2012

and June 2014. In these centers, current practices were similar, with at least three separate consultations (information and genetic test uptake; mutation status disclosure and confirmation test uptake; mutation status confirmation). Patients received a medical report after each consultation and a copy of their test results. All French geneticists follow the guidelines of the French National Institute of Cancer. Since 2013, patients are informed about their legal duty to inform their relatives about the availability of GTT.¹⁵

Patients were eligible if they (a) carried a pathogenic variant in *BRCA1* (MIM*113705) or *BRCA2* (MIM*600185) or in MMR genes [MLH1 (MIM*120436), MSH2 (MIM*609309), MSH6 (MIM*600678), PMS2 (MIM*600259)]; (b) had a diagnosis for more than 3 months, to have sufficient time to communicate with their at-risk relatives; (c) were the first family member informed about the pathogenic variant; (d) were aged 18 years and over; and (e) had social insurance. Genetic tests are fully covered by the French public health care system, available to all citizens. No commercial tests are available in the country.

Eligible patients received a letter describing the study and asking if they accepted to be contacted. Those who sent their agreement by the given reply-paid envelope were contacted by a clinical research assistant giving them complete information and inviting them for an on-site main interview. During this interview, clinical research assistants asked probands about intrafamilial disclosure, uptake of GTT in their family, and collected sociodemographic and clinical data. Psychological questionnaires were fulfilled by patients in a dedicated room, with no time limit. Beforehand, interviewers had undergone training together in order to harmonize the survey's presentation and limit reporting bias. For patients who could not visit the hospital, psychological questionnaires were sent to their homes, and sociodemographic and clinical data were completed during a telephone interview. Three months after their inclusion, probands were contacted by phone and asked if they estimate the study had reopened communication about GTT (yes/no) and, if so, if new tests have been performed to their knowledge (yes/no).

# 3 | MEASURES

## 3.1 | Primary outcomes

(a) The intrafamilial disclosure rate assessed the number of relatives informed by the proband about the mutation (reported by the proband during the main interview) out of the number of relatives at risk of carrying the familial mutation. At-risk relatives were first, second, third, or fourth-degree adult relatives from the relevant side of the family or, if unknown, just related to the proband whatever the family side. (b) The relatives' GTT uptake rate assessed the proband-reported number of relatives who took up GTT out of the number of relatives informed by the proband. To assess the potential information bias of the relatives' GTT uptake rate, we compared the number of relatives who underwent GTT according to the proband with the number of tests actually performed. This anonymous comparison was performed in a
subset of the population within the geographic regional area of Montpellier where all analyses are centralized in a single laboratory. Probands were asked how many relatives living in the region underwent genetic testing, and this number was compared with the information available from the University Laboratory of Montpellier.

**3.1.1 | Sociodemographic and clinical data**

Probands' age, gender, marital status, and level of education were collected. Clinical data included patients' *BRCA1/2* or MMR genetics analysis results, cancer(s) diagnosis (es), therapies, and any recurrence of cancer. We also indexed the family cancer history related to the mutation spectrum (for *BRCA1/2*: breast, ovaries, prostate, and other specific locations; for MMR: bowel, rectum, endometrium, ovaries, and other specific locations). We also asked them if a new familial cancer was diagnosed among relatives since their mutation diagnosis and if they estimate that this event revived intrafamilial communication about GTT.

**3.1.2 | Psychosocial factors**

Validated French versions of questionnaires were used to assess depressive symptoms (Beck Depression Inventory²²), dispositional anxiety (Spielberger Trait Anxiety Inventory subscale²³), optimism (Life Orientation Test Revised²⁴), alexithymia (Toronto Alexithymia Scale²⁵), emotional awareness (Levels of Emotional Awareness Scale²⁶), coping styles (35-item version of the Ways of Coping Checklist Trait²⁷), and family relationships (Family Relationship Index²⁸ including family cohesion, expressiveness, and conflict subscales).²⁸

Visual analog scales (VAS) were used to assess the perception of cancer risks associated with the mutation spectrum, the perception of the risk of hereditary transmission, and the messenger task perception, through the three following questions: "As far as you can remember, at the moment of your genetic result disclosure, how did you estimate your risk to develop a/an [specific type] cancer?" (VAS from 0% to 100%); "At the moment of your mutation status disclosure, how did you estimate the probability that your children might be carriers too?" (VAS from 0% to 100%); "How easily did you fulfill your messenger task?" (VAS, from 0, very easy, to 10, very difficult).

**3.1.3 | Statistical analysis**

The study population is described with means (SD) for quantitative variables and frequencies (%) for categorical variables. The continuous variable distribution was tested with the Shapiro-Wilk test. Comparison between *BRCA1/2* and MMR groups for quantitative variables involved Student t test when the distribution was Gaussian and the Mann-Whitney test otherwise. For categorical variables, groups were compared by chi-square test or Fisher exact test. The two-sided Jonckheere trend test was used to investigate the existence of an intrafamilial disclosure rate trend according to family degree. The concordance between the number of targeted tests declared by the proband in Montpellier and that checked by the corresponding laboratory was analyzed by the intraclass correlation coefficient along with its 95% confidence interval. A coefficient above 0.8, 0.6, and 0.4 is considered as measuring, respectively, a "near perfect," "important," and "moderate" concordance.

<figure><img src="image_2.png" /><figcaption>**FIGURE 1** Flow chart of the study population</figcaption></figure>
To identify the potential psychosocial, sociodemographic, and clinical characteristics of probands associated with intrafamilial disclosure and GTT uptake, multiple linear regression models were used. Dependent variables were the linearization of those percentages (arsin(√(percentage))). For perception of hereditary transmission, perception of "messenger task" (cm), and perception of cancer risk, missing values were imputed by multiple linear regression. Relevant variables with $P \le .20$ on univariate analysis were included in the multivariable model. The final model was determined by backward selection with a removal level of 0.10. Correlations between variables remaining in final multivariable models were analyzed by the Spearman coefficient. Two-sided significance level was 0.05. SAS v9.4 (SAS Inst., Cary, NC) was used for analysis.

# 4 | RESULTS

## 4.1 | Proband characteristics

We included 103 probands, of which 78.6% with a *BRCA1/2* mutation and 21.4% with a MMR gene mutation (Figure 1). Proband

characteristics are in Table 1. The survey was conducted a mean of 4 years after genetic diagnosis of probands. None of the psychological variables assessed differed between MMR and *BRCA1/2* probands, except for the alexithymia subscore, "difficulty describing feelings," which was greater in MMR than *BRCA1/2* probands ($P = .03$) (data not shown). This difference does not seem to be due to sex differences between MMR and *BRCA1/2* groups, because this subscore was similar between men and women in the MMR subgroup (15.1 and 15.8, respectively).

## 4.2 | Intrafamilial disclosure and uptake of GTT

The mean intrafamilial disclosure rate in the overall population was 68%, and the mean GTT uptake rate among informed relatives was 37% (Table 2). Among the 51 families included in the Hospital of Montpellier, the concordance between the number of tests reported by the proband and the number reported with the lab was considered good, with an intraclass correlation coefficient of 0.77 (95% confidence interval 0.63-0.86), despite several outliers (Figure S1).

Intrafamilial disclosure and GTT uptake rates did not differ significantly between *BRCA1/2* and MMR groups (66% and 74%, 36% and

<table><caption>TABLE 1 Characteristics of probands overall and by *BRCA1/2* and mismatch repair (MMR) families</caption><thead><tr><th>Demographic Characteristics</th><th>Overall Population N = 103</th><th>BRCA1/2 N = 81</th><th>MMR N = 22</th><th>P-Value</th></tr></thead><tbody><tr><td>Age (years)</td><td>55.2 ± 10.4</td><td>54.7 ± 10.0</td><td>57.1 ± 12.1</td><td>NS</td></tr><tr><td>Female gender</td><td>92 (89)</td><td>80 (99)</td><td>12 (55)</td><td>&lt;0.001</td></tr><tr><td>Time since mutation disclosure (years)</td><td>3.9 ± 2.4</td><td>4.0 ± 2.5</td><td>3.5 ± 1.9</td><td>NS</td></tr><tr><td>Marital status</td><td></td><td></td><td></td><td></td></tr><tr><td>Married or living with a partner</td><td>76 (75)</td><td>58 (72)</td><td>18 (82)</td><td>NS</td></tr><tr><td>Other</td><td>26 (25)</td><td>22 (28)</td><td>4 (18)</td><td></td></tr><tr><td>Having at least 1 child</td><td>96 (93)</td><td>75 (93)</td><td>21 (95)</td><td>NS</td></tr><tr><td>Education level</td><td></td><td></td><td></td><td></td></tr><tr><td>No high school education</td><td>35 (34)</td><td>24 (30)</td><td>11 (50)</td><td>NS</td></tr><tr><td>High school and up to 2 years of undergraduate studies</td><td>30 (29)</td><td>26 (32)</td><td>4 (18)</td><td></td></tr><tr><td>Over 2 years of undergraduate studies</td><td>38 (37)</td><td>31 (38)</td><td>7 (39)</td><td></td></tr><tr><td>Genetic center</td><td></td><td></td><td></td><td></td></tr><tr><td>Montpellier</td><td>51 (50)</td><td>43 (53)</td><td>8 (36)</td><td>NS</td></tr><tr><td>Nîmes</td><td>21 (20)</td><td>14 (17)</td><td>7 (32)</td><td></td></tr><tr><td>Clermont-Ferrand</td><td>31 (30)</td><td>24 (30)</td><td>7 (32)</td><td></td></tr><tr><td>Personal medical history</td><td></td><td></td><td></td><td></td></tr><tr><td>Personal history of cancer</td><td>98 (95)</td><td>77 (95)</td><td>21 (95)</td><td>NS</td></tr><tr><td>One recurrence or second localisation of cancer</td><td>39 (40)</td><td>29 (38)</td><td>10 (48)</td><td>NS</td></tr><tr><td>Family medical history<sup>a</sup></td><td></td><td></td><td></td><td></td></tr><tr><td>No. of cancer(s)</td><td></td><td></td><td></td><td></td></tr><tr><td>1-3</td><td>-</td><td>52 (65)</td><td>9 (43)</td><td>0.06</td></tr><tr><td>≥4</td><td>-</td><td>28 (35)</td><td>12 (57)</td><td></td></tr><tr><td>No. of cancer(s) among first and second degree relatives</td><td>-</td><td>2.6 ± 1.5</td><td>3.8 ± 2.4</td><td>0.03</td></tr><tr><td>No. of relatives who died due to cancer</td><td>-</td><td>1.6 ± 1.5</td><td>2.0 ± 1.8</td><td>NS</td></tr></tbody></table>

Data are N (%) or mean ± SD.

<footnote><sup>a</sup>Cancers related to mutation spectrum are defined in Methods. NS: non-significant ($P > .05$); MMR: mismatch-repair.</footnote>
<table><caption>TABLE 2 Intrafamilial disclosure and uptake of genetic targeted testing (GTT) among BRCA1/2 and MMR families</caption><thead><tr><th></th><th>N</th><th>Global</th><th>N</th><th>BRCA1/2</th><th>N</th><th>MMR</th><th>P-Value*</th></tr></thead><tbody><tr><td>Intrafamilial disclosure (%)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Globally</td><td>103</td><td>68 (±28)</td><td>81</td><td>66 (±28)</td><td>22</td><td>74 (±26)</td><td>0.32</td></tr><tr><td>First-degree relatives</td><td>101</td><td>95 (±12)</td><td>79</td><td>94 (±13)</td><td>22</td><td>98 (±6)</td><td>0.23</td></tr><tr><td>Second-degree relatives</td><td>94</td><td>73 (±37)</td><td>72</td><td>71 (±38)</td><td>22</td><td>79 (±35)</td><td>0.40</td></tr><tr><td>Third-degree relatives</td><td>70</td><td>59 (±44)</td><td>56</td><td>58 (±44)</td><td>14</td><td>61 (±45)</td><td>0.93</td></tr><tr><td>Fourth-degree relatives</td><td>26</td><td>44 (±47)</td><td>23</td><td>37 (±45)</td><td>3</td><td>100 (±0)</td><td>0.03</td></tr><tr><td>P-value (trend test) **</td><td></td><td>&lt;.001</td><td></td><td>&lt;.001</td><td></td><td>&lt;.01</td><td></td></tr><tr><td>GTT uptake among informed relatives (%)</td><td>103</td><td>37 (±31)</td><td>81</td><td>36 (±31)</td><td>22</td><td>40 (±30)</td><td>0.55</td></tr><tr><td>GTT uptake among eligible relatives (%)</td><td>103</td><td>25 (±23)</td><td>81</td><td>24 (±22)</td><td>22</td><td>30 (±26)</td><td>0.29</td></tr></tbody></table>

Data are mean (±SD). GTT, genetic targeted testing; MMR, mismatch repair.

*P-value compares mean intrafamilial disclosure rate between BRCA and MMR groups.

**P-value corresponds to trend in disclosure rate by family degree. The significant fourth-degree result in the MMR subgroup should not be considered because of insufficient sample size.

40%, respectively). For both BRCA1/2 and MMR patients, intrafamilial disclosure rate decreased gradually with degree of kinship (P < .0001): first-degree at-risk relatives were mostly all informed (95%), but less than half of fourth-degree at-risk relatives were informed (44%) (Table 2). Intrafamilial disclosure and GTT uptake rates did not differ significantly between men and women of the MMR subgroup (76% and 72%, 35% and 44%, respectively).

## 4.3 | Factors associated with intrafamilial disclosure (Table S1)

Poor perception of messenger task and poor perception of hereditary transmission were significantly associated with decreased intrafamilial disclosure on univariate analysis but not after adjustment for other factors. On multivariable analysis, intrafamilial disclosure rate was positively associated with time since mutation disclosure (β = 0.06, SD = ±0.01, P < .01) and family cohesion score (β = 0.04, SD = ±0.01, 0.01)

Among 90 patients who responded, 33 reported at least a new cancer occurrence in their family; 10/33 (30.3%) estimated this event re-opened communication about genetic tests between them and their family members.

## 4.4 | Factors associated with relative GTT uptake (Table S1)

GTT uptake was associated with levels of optimism on univariate but not in multivariable analysis. On multivariable analysis, GTT uptake was decreased with probands' high perception of cancer risks (β = -0.002, ±SD = 0.001, 0.04) and increased with probands' depressive symptoms (β = 0.02, SD = ±0.01, 0.02).

Among the four factors associated with intrafamilial disclosure or GTT uptake in multivariable analyses, we only found a negative

correlation between family cohesion and depressive symptoms (r = -0.30, P = .003).

## 4.5 | Three-month follow-up data

Of the 101 patients contacted by phone 3 months after the first interview, 81(80%) responded. Among them, 51.8% (42/81) claimed to have talked again to their relatives about genetic testing, and new GTT uptake events were reported for 12/42 of the families concerned (28.5%).

## 5 | CONCLUSIONS

This prospective multicentric survey addressed the question of genetic information disclosure by probands and uptake of genetic testing by relatives among 103 French families with BRCA1/2 or MMR gene mutations.

According to probands, 68% of relatives were informed of the family genetic risk, and only 37% of these underwent GTT. These results are consistent with our previous nationwide study showing one third of informed relatives undergoing GTT.² The good concordance between the rate of GTT uptake reported by the proband and the number of tests actually performed strengthens these data. A previous study showed higher rates of GTT uptake when the information of all relatives was ensured by proactive approaches.²⁹ We also confirmed the decreased rate of family information with generational remoteness.³,¹⁰,¹¹

Mean time since mutation disclosure was positively associated with intrafamilial disclosure. Even though a majority of probands wish to communicate about genetic risks, they often wait to find the “right moment” to share such news, often anticipated as stressful.¹³,³⁰,³¹ Moreover, a third of probands reporting at least one new case of familial cancer since their mutation diagnosis (n = 33) estimated that this event revived the family communication about GTT. Indeed,
certain life events such as relative's cancer diagnosis or death may open a "window of opportunity" for family communication about cancer risks.³² In addition, among probands recontacted by phone 3 months after the first interview, 52% declared re-opening the subject about GTT with their family, and 29% of them reported at least one new GTT uptake in their family. Information disclosure is therefore a continuous and dynamic process, evolving with time and with certain life events or new interactions with professionals.

We also confirmed that the quality of family relationships—evaluated with the FRI scale—was associated with a higher intrafamilial disclosure.⁷,³³ Prior studies suggested that the need of emotional support is an important motivation in sharing genetic results.⁸ In a family perceived as cohesive, where probands can find support and sense of unity, it may be easier to share tests results, overcoming potential fears to cause distress. Moreover, probands feeling part of a cohesive family may have a better perception of their relatives' opinions regarding genetic testing, which is known to increase intrafamilial disclosure.⁷,⁸,¹⁹

GTT uptake by at-risk relatives was negatively affected by probands' high perception of cancer risks. This raises the question of whether and how probands' perception could influence the information provided to family members and their decisions about GTT.¹⁷,³⁴ Genetic information is medically and emotionally complex, and patients may cope with different "disclosure dilemmas" when they have to convey it.⁹,³¹,³⁵ The information, potentially transformed by probands' personal interpretations or emotions, might also be misunderstood or misinterpreted by relatives.³⁶ However, further studies, including qualitative ones, are needed to explore the interaction between probands who have a high perception of genetic risks and their family members.

Surprisingly, probands' depressive symptoms were positively associated with GTT uptake, unlike previous reports.¹⁹,²⁰ As probands' depressive symptoms were negatively correlated with the "family cohesion" subscore, we can hypothesize that these patients, who suffer from cancer, feel depressed, and do not feel part of a cohesive family, may disclose genetic information partly to get out of isolation and strongly persuade their relatives of the family dimension of their own situation. Nonetheless, these results have to be interpreted with caution because they impact only indirectly the relatives' decision to uptake GTT. Further research is also needed to better understand the interaction between such probands and their family members.

We found that probands' anxiety was not associated with intrafamilial disclosure and GTT uptake in multivariable analysis, as previously reported.¹⁰,²¹ Other sociodemographic characteristics and psychological variables did not impact intrafamilial disclosure or GTT uptake. Given that patients with alexithymia have more difficulties to identify and express emotions, a lower intrafamilial disclosure could have been expected in their families, which was not the case. Coping styles were not associated with intrafamilial disclosure as shown by other studies.¹⁰,¹⁸

Intrafamilial disclosure did not differ significantly between BRCA1/2 and MMR families despite different prevention strategies and psychological benefits associated with genetic testing.¹⁶ Overall GTT

uptake in MMR families was not significantly higher, despite MMR-related risk equally affects women and men whereas BRCA1/2 mainly affects women. A lack of GTT uptake among males in MMR families as compared with females could be a possible explanation.³⁷ Furthermore, studies showed that cancer screening may be perceived as a taboo subject.³⁸,³⁹ This attitude could complicate the messenger task, leading to avoidance behaviors both in probands and family members. Finally, none of the assessed psychological variables differed between BRCA1/2 and MMR probands, except for the alexithymia subscore "difficulty describing feelings," which was greater for MMR than BRCA1/2 probands. This might be linked with a potential difficulty communicating about colorectal cancer or screening, which are sensitive topics. Concerning this result, a gender effect was not proven, but the sample size of the MMR subgroup was small.

## 5.1 | Study limitations

The present work is subject to recruitment bias, as enrolled probands may be more "communicative" than nonrespondents. Moreover, our results may not be completely generalizable due to the recent French decree framing intrafamilial disclosure.¹⁵ In addition, we assessed self-reported intrafamilial disclosure and uptake of GTT, which may differ from actual data. Nevertheless, to our knowledge, our study is the first to have verified the validity of proband's declaration about GTT uptake, for almost half of our overall sample. No data were collected about relatives who could have been informed by nonproband relatives. Psychological variables were assessed by validated standardized tools. However, potential recall bias may have occurred, as our interviews sometimes occurred several years after the mutation disclosure, with no baseline measures. Lastly, we studied probands' psychosocial characteristics, but relatives' uptake of GTT could also be linked to other factors such as their personal characteristics or opinions about GTT, not explored in this study.⁴⁰

## 5.2 | Clinical implications

Identification of factors affecting disclosure to relatives and GTT uptake gives insights to improve the personalization of probands' support and the intrafamilial sharing of genetic information. Literature data on psychological predictors of intrafamilial disclosure and GTT uptake are heterogeneous,⁴,¹⁰,¹⁸⁻²⁰ probably due to the use of different tools, populations, and study designs. Nevertheless, our study supports that high familial cohesion, time since diagnosis, and poor subjective perception of cancer risk improve intrafamilial disclosure and/or GTT, whereas other factors such as probands' anxiety, optimism, or alexithymia do not seem to have any impact. Probands do have a key role, especially in France where the duty to inform is now regulated by a decree. Thinking about ways to lighten the "messenger task," perhaps by encouraging a form of "messenger solidarity," seems interesting. Exploring the family history with patients not only in a quantitative but also in qualitative way (who talks to who, who could help them to disseminate the information?) could be a
precious resource. Intrafamilial disclosure seems to be a continuous and dynamic process. Indeed, patients do not assimilate and communicate potentially stressful information the same way at each step of their illness or remission and must be supported over the long term. As genetic centers become more and more overloaded with the increase in predictive medicine tasks, the increasing involvement of other health professionals (involved in cancer screening or general practitioners), who generally meet patients more regularly,³⁷ seems crucial.

## ACKNOWLEDGEMENTS

We sincerely thank patients for their participation in the study. This work was supported by grants from La Ligue Contre Le Cancer (#PRSH11/99) and from AstraZeneca (#2014-00290).

## CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest with industry or firms commercializing genetic tests. Pr Pujol discloses attending Advisory Board Membership for AstraZeneca, Pfizer, Roche, and Genomic Health.

## ETHICS AND PATIENTS CONSENT

The study was approved by the institutional ethics review board of the University Hospital of Nîmes ("Comité de Protection des Personnes") under the 2012.05.01 number of approval. All procedures performed in this study were in accordance with the Law n°2004-806 of 9 August 2004 concerning the Public Health Policy. Every patient included in the study completed an informed consent form.

## DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

## ORCID

Nathalie Alegre https://orcid.org/0000-0001-5823-6559

## REFERENCES

1. Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304(9):967-975.

2. Pujol P, Lyonnet DS, Frebourg T, et al. Lack of referral for genetic counseling and testing in BRCA1/2 and Lynch syndromes: a nationwide study based on 240,134 consultations and 134,652 genetic tests. Breast Cancer Res Treat. 2013;141(1):135-144.

3. Lieberman S, Lahad A, Tomer A, et al. Familial communication and cascade testing among relatives of BRCA population screening participants. Genet Med. 2018;20(11):1446-1454.

4. Cheung EL, Olson AD, Yu TM, Han PZ, Beattie MS. Communication of BRCA results and family testing in 1,103 high-risk women. Cancer Epidemiol Biomarkers Prev. 2010;19(9):2211-2219.

5. Julian-Reynier C, Sobol H, Sevilla C, Nogues C, Bourret P, French Cancer Genetic N. Uptake of hereditary breast/ovarian cancer genetic

testing in a French national sample of BRCA1 families. The French Cancer Genetic Network. Psychooncology. 2000;9(6):504-510.

6. Aktan-Collan KI, Kaariainen HA, Kolttola EM, et al. Sharing genetic risk with next generation: mutation-positive parents' communication with their offspring in Lynch syndrome. Fam Cancer. 2011;10(1):43-50.

7. Wiseman M, Dancyger C, Michie S. Communicating genetic risk information within families: a review. Fam Cancer. 2010;9(4):691-703.

8. Finlay E, Stopfer JE, Burlingame E, et al. Factors determining dissemination of results and uptake of genetic testing in families with known BRCA1/2 mutations. Genet Test. 2008;12(1):81-91.

9. Peters JA, Kenen R, Hoskins LM, et al. Unpacking the blockers: understanding perceptions and social constraints of health communication in hereditary breast ovarian cancer (HBOC) susceptibility families. J Genet Couns. 2011;20(5):450-464.

10. Claes E, Evers-Kiebooms G, Boogaerts A, Decruyenaere M, Denayer L, Legius E. Communication with close and distant relatives in the context of genetic testing for hereditary breast and ovarian cancer in cancer patients. Am J Med Genet A. 2003;116A(1):11-19.

11. Stoffel EM, Ford B, Mercado RC, et al. Sharing genetic test results in Lynch syndrome: communication with close and distant relatives. Clin Gastroenterol Hepatol. 2008;6(3):333-338.

12. McGivern B, Everett J, Yager GG, Baumiller RC, Hafertepen A, Saal HM. Family communication about positive BRCA1 and BRCA2 genetic test results. Genet Med. 2004;6(6):503-509.

13. Green J, Richards M, Murton F, Statham H, Hallowell N. Family communication and genetic counseling: the case of hereditary breast and ovarian cancer. J Genet Couns. 1997;6(1):45-60.

14. DudokdeWit AC, Tibben A, Frets PG, et al. BRCA1 in the family: a case description of the psychological implications. Am J Med Genet. 1997;71(1):63-71.

15. Official Journal of the French Republic. Decree 2013-527 of 20 June 2013 on the conditions for the information of relatives in the context of an examination of genetic characteristics with a medical purpose. Articles R.1131-20-1 to 1131-20-5. https://www.legifrance.gouv.fr/affichTexte.do?cidTexte=JORFTEXT000027592003

16. Meiser B. Psychological impact of genetic testing for cancer susceptibility: an update of the literature. Psychooncology. 2005;14(12):1060-1074.

17. Elrick A, Ashida S, Ivanovich J, et al. Psychosocial and clinical factors associated with family communication of cancer genetic test results among women diagnosed with breast cancer at a young age. J Genet Couns. 2017;26(1):173-181.

18. Kegelaers D, Merckx W, Odeurs P, van den Ende J, Blaumeiser B. Disclosure pattern and follow-up after the molecular diagnosis of BRCA/CHEK2 mutations. J Genet Couns. 2014;23(2):254-261.

19. Montgomery SV, Barsevick AM, Egleston BL, et al. Preparing individuals to communicate genetic test results to their relatives: report of a randomized control trial. Fam Cancer. 2013;12(3):537-546.

20. Landsbergen K, Verhaak C, Kraaimaat F, Hoogerbrugge N. Genetic uptake in BRCA-mutation families is related to emotional and behavioral communication characteristics of index patients. Fam Cancer. 2005;4(2):115-119.

21. Julian-Reynier C, Eisinger F, Chabal F, et al. Disclosure to the family of breast/ovarian cancer genetic test results: patient's willingness and associated factors. Am J Med Genet. 2000;94(1):13-18.

22. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4(6):561-571.

23. Spielberger CD, Gorsuch RL. Manual for the State-trait Anxiety Inventory (form Y) ("Self-Evaluation Questionnaire"). Palo Alto, CA: Consulting Psychologists Press; 1983.
24. Scheier MF, Carver CS, Bridges MW. Distinguishing optimism from neuroticism (and trait anxiety, self-mastery, and self-esteem): a reevaluation of the life orientation test. *J Pers Soc Psychol.* 1994;67(6):1063-1078.

25. Bagby RM, Parker JD, Taylor GJ. The twenty-item Toronto Alexithymia Scale—I. Item selection and cross-validation of the factor structure. *J Psychosom Res.* 1994;38(1):23-32.

26. Lane RD, Quinlan DM, Schwartz GE, Walker PA, Zeitlin SB. The levels of emotional awareness scale: a cognitive-developmental measure of emotion. *J Pers Assess.* 1990;55(1-2):124-134.

27. Folkman S, Lazarus RS. If it changes it must be a process: study of emotion and coping during three stages of a college examination. *J Pers Soc Psychol.* 1985;48(1):150-170.

28. Moos RH. Conceptual and empirical approaches to developing family-based assessment procedures: resolving the case of the family environment scale. *Fam Process.* 1990;29(2):199-208; discussion 9-11.

29. Evans DG, Binchy A, Shenton A, Hopwood P, Craufurd D. Comparison of proactive and usual approaches to offering predictive testing for BRCA1/2 mutations in unaffected relatives. *Clin Genet.* 2009;75(2):124-132.

30. Forrest K, Simpson SA, Wilson BJ, et al. To tell or not to tell: barriers and facilitators in family communication about genetic risk. *Clin Genet.* 2003;64(4):317-326.

31. Clarke S, Butler K, Esplen MJ. The phases of disclosing BRCA1/2 genetic information to offspring. *Psychooncology.* 2008;17(8):797-803.

32. Lapointe J, Cote C, Bouchard K, Godard B, Simard J, Dorval M. Life events may contribute to family communication about cancer risk following BRCA1/2 testing. *J Genet Couns.* 2013;22(2):249-257.

33. Koehly LM, Peterson SK, Watts BG, Kempf KK, Vernon SW, Gritz ER. A social network analysis of communication about hereditary nonpolyposis colorectal cancer genetic testing and family functioning. *Cancer Epidemiol Biomarkers Prev.* 2003;12:304-313.

34. Gaff CL, Clarke AJ, Atkinson P, et al. Process and outcome in communication of genetic information within families: a systematic review. *Eur J Hum Genet.* 2007;15(10):999-1011.

35. Forrest LE, Curnow L, Delatycki MB, Skene L, Aitken M. Health first, genetics second: exploring families' experiences of communicating genetic information. *Eur J Hum Genet.* 2008;16(11):1329-1335.

36. Daly MB, Montgomery S, Bingler R, Ruth K. Communicating genetic test results within the family: is it lost in translation? A survey of relatives in the randomized six-step study. *Fam Cancer.* 2016;15(4):697-706.

37. Barrow P, Green K, Clancy T, Lalloo F, Hill J, Evans DG. Improving the uptake of predictive testing and colorectal screening in lynch syndrome: a regional primary care survey. *Clin Genet.* 2015;87(6):517-524.

38. McCann S, MacAuley D, Barnett Y, et al. Family communication, genetic testing and colonoscopy screening in hereditary non-polyposis colon cancer: a qualitative study. *Psychooncology.* 2009;18(11):1208-1215.

39. Teixeira C, Martins C, Trabulo D, et al. Colorectal cancer screening: what is the population's opinion. *GE Port J Gastroenterol.* 2018;25(2):62-67.

40. Biesecker BB, Ishibe N, Hadley DW, et al. Psychosocial factors predicting BRCA1/BRCA2 testing decisions in members of hereditary breast and ovarian cancer families. *Am J Med Genet.* 2000;93(4):257-263.

## SUPPORTING INFORMATION

Additional supporting information may be found online in the Supporting Information section at the end of the article.

**How to cite this article:** Alegre N, Perre PV, Bignon YJ, et al. Psychosocial and clinical factors of probands impacting intrafamilial disclosure and uptake of genetic testing among families with BRCA1/2 or MMR gene mutations. *Psycho-Oncology.* 2019;28:1679-1686. https://doi.org/10.1002/pon.5142