Family Adjustment to Hereditary Cancer Syndromes: A Systematic Review

Abstract

Hereditary cancer syndromes are inherited pathogenic genetic variants that significantly increase the risk of developing cancer. When individuals become aware of their increased probability of having cancer, the whole family is affected by this new reality and needs to adjust. However, adjustment to hereditary cancer syndromes has been mainly studied at an individual level, and research about familial adjustment remains dispersed and disorganized. To overcome this gap, this review aims to understand how families adjust to genetic testing and risk management, and to what extent the family's adjustment influences the psychological response and risk management behaviors of mutation carriers. We conducted searches on the PubMed/Med Line, PsycInfo, SCOPUS, and Google Scholar databases and used the Mixed Methods Appraisal Tool (MMAT-v2018) to assess the methodological quality of each selected study. Thirty studies met the inclusion criteria. Most results highlighted the interdependent nature of adjustment of pathogenic variant carriers and their families. The way carriers adjust to the syndrome is highly related to how family members react, particularly partners and siblings dependent on prior family functioning. Couples who share their worries and communicate openly about cancer risk present a better long-term adjustment than couples who use protective buffering (not talking about it to avoid disturbing the partner) or emotional distancing. Parents need help dealing with disclosing genetic information to their children. These findings reinforce the importance of adopting a family-centered approach in the context of genetic counseling and the necessity of involving family members in research.

Full text

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Citation: Gomes, P.; Pietrabissa, G.;
Silva, E.R.; Silva, J.; Matos, P.M.;
Costa, M.E.; Bertuzzi, V.; Silva, E.;
Neves, M.C.; Sales, C.M.D. Family
Adjustment to Hereditary Cancer
Syndromes: A Systematic Review.
Int. J. Environ. Res. Public Health 2022,
19, 1603. https://doi.org/10.3390/
ijerph19031603
Academic Editor: M. Graça Pereira
Received: 1 December 2021
Accepted: 24 January 2022
Published: 30 January 2022
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4.0/).
International Journal of
Environmental Research
and Public Health
Review
Family Adjustment to Hereditary Cancer Syndromes:
A Systematic Review
Pedro Gomes 1, 2,*, Giada Pietrabissa 3,4 , Eunice R. Silva 1,5, João Silva 1,6, Paula Mena Matos 2,
Maria Emília Costa 2, Vanessa Bertuzzi 3, Eliana Silva 2, Maria Carolina Neves 1,2 and Célia M. D. Sales 2
1
Cancer Genetics Group, Research Centre of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network),
Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto.CCC),
4200-072 Porto, Portugal; esilva@ipoporto.min-saude.pt (E.R.S.);
joao.pinho.silva@ipoporto.min-saude.pt (J.S.); marianeves@fpce.up.pt (M.C.N.)
2Centre for Psychology at University of Porto (CPUP), Faculty of Psychology and Education Sciences at
University of Porto (FPCEUP), 4200-135 Porto, Portugal; pmmatos@fpce.up.pt (P.M.M.);
ecosta@fpce.up.pt (M.E.C.); elianasilva@fpce.up.pt (E.S.); celiasales@fpce.up.pt (C.M.D.S.)
3Department of Psychology, Catholic University of the Sacred Heart, 20123 Milan, Italy;
Giada.Pietrabissa@unicatt.it (G.P.); vanessa.bertuzzi@unicatt.it (V.B.)
4Psychology Research Laboratory, IRCCS Istituto Auxologico Italiano, 20122 Milan, Italy
5Psychology Service, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
6Medical Genetics Service, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
*Correspondence: pedrogomes@fpce.up.pt
Abstract:
Hereditary cancer syndromes are inherited pathogenic genetic variants that significantly
increase the risk of developing cancer. When individuals become aware of their increased probability
of having cancer, the whole family is affected by this new reality and needs to adjust. However,
adjustment to hereditary cancer syndromes has been mainly studied at an individual level, and
research about familial adjustment remains dispersed and disorganized. To overcome this gap, this
review aims to understand how families adjust to genetic testing and risk management, and to what
extent the family’s adjustment influences the psychological response and risk management behaviors
of mutation carriers. We conducted searches on the PubMed/Med Line, PsycInfo, SCOPUS, and
Google Scholar databases and used the Mixed Methods Appraisal Tool (MMAT-v2018) to assess the
methodological quality of each selected study. Thirty studies met the inclusion criteria. Most results
highlighted the interdependent nature of adjustment of pathogenic variant carriers and their families.
The way carriers adjust to the syndrome is highly dependent on family functioning and related to how
family members react to the new genetic information, particularly partners and siblings. Couples who
share their worries and communicate openly about cancer risk present a better long-term adjustment
than couples who use protective buffering (not talking about it to avoid disturbing the partner) or
emotional distancing. Parents need help dealing with disclosing genetic information to their children.
These findings reinforce the importance of adopting a family-centered approach in the context of
genetic counseling and the necessity of involving family members in research.
Keywords:
hereditary cancer syndromes; genetic testing; family adjustment; cancer risk management;
decision-making; genetic counseling
1. Introduction
Nearly five to ten percent of all cancers are hereditary and caused by genetic pathogenic
variants that significantly increase the lifetime risk of cancer when compared to the general
population [
1
]. To identify whether an individual carries a pathogenic variant that increases
the risk of cancer, geneticists may prescribe genetic tests for cancer susceptibility to indi-
viduals from hereditary cancer families [
2
,
3
]. When a healthy individual is identified as a
pre-symptomatic pathogenic variant carrier, cancer risk may be reduced through enhanced
Int. J. Environ. Res. Public Health 2022,19, 1603. https://doi.org/10.3390/ijerph19031603 https://www.mdpi.com/journal/ijerph

Int. J. Environ. Res. Public Health 2022,19, 1603 2 of 22
surveillance procedures (e.g., regular colonoscopies), pharmacy chemoprevention, and/or
prophylactic surgeries (e.g., mastectomies) [
4
,
5
]. Additionally, family planning solutions,
such as medically assisted reproduction, may be offered to prevent future children from
carrying the pathogenic variant [
6
]. However, although preventing cancer onset is crucial
for pathogenic variant carriers, knowing about future cancer risk, deciding on the personal
prevention plan, and adapting to risk-reduction measures pose significant psychological
challenges [
7
–
11
]. In fact, deciding if, how, and when to undergo the invasive medical
procedures usually reserved for these situations [
4
,
12
] may not only elicit distress in the
pathogenic variant carriers [13] but also in their family members [14].
Therefore, the aftermath of a positive genetic testing result commonly represents
a critical event for the whole family [
15
]. Not only as it has the potential to impact the
health of family members who may also be carrying the pathogenic variant, but it may
also affect family members’ relationships and a couple’s reproductive decisions [
16
,
17
]. In
addition, genetic testing uptake is usually carried out in a cascading way [
18
], which often
means that the new pathogenic variant carriers vicariously experience the outcome of their
carrier relatives’ decisions [
14
]. In this sense, dealing with the uncertainty of possible future
losses without abdicating from important life cycle goals (e.g., having children) requires
pathogenic variant carriers and their family members to develop great flexibility in an
inter-related adjustment process [
19
,
20
]. In other words, to understand the psychological
adjustment to inherited cancer risk, one must conceive it as a systemic phenomenon [
19
–
21
].
Previous systematic reviews have already summarized the existing knowledge con-
cerning the psychological adjustment of the applicant to genetic testing and counsel-
ing
[22–28]
and on the effectiveness of interventions to help pathogenic variant carrier
health-related decision-making processes [
29
]. However, studies on familial adjustment
in the face of inherited genetic syndromes remain dispersed and disaggregated. To our
knowledge, to date, only one review [
30
] focused on familial adjustment to hereditary
cancer syndromes. Additionally, this contribution only explored the experiences of male
partners of hereditary breast and ovarian cancer syndrome carriers.
Intending to address this gap, the present systematic review organizes current knowl-
edge on the topic of familial adjustment to hereditary cancer syndromes in a rigorous and
replicable way. Our objective is to review findings from existing research investigating the
psychological adjustment of the families of pre-symptomatic pathogenic variant carriers
to an increased susceptibility to hereditary cancer. Specifically, we focused on the period
following a positive genetic test, including the long-term adjustment to personalized pre-
vention programs to understand: (1) how do families adjust to a positive genetic test result
of a pre-symptomatic member and his/her risk management behaviors? (2) to what extent
does the family influence the psychological adjustment and risk management behaviors of
the pre-symptomatic pathogenic variant carrier?
2. Method
This systematic review was registered with PROSPERO (ID CRD42020142200). Data
extraction, critical appraisal, and qualitative synthesis followed established systematic
review and qualitative synthesis methods [
31
] and the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) statement [32].
2.1. Search Strategy
We conducted searches in the following databases: PubMed/MEDLINE, Scopus,
PsycInfo, and Google Scholar between 28 June to 2 July 2019, which were updated between
the 13 and 17 January 2020, and again between 23 June and 2 July 2021 and complemented
with hand-searching. The search strategies combined key terms and Medical Search Head-
ings (MESH) terms for the concepts of inherited cancer risk, unaffected pathogenic variant
carrier, emotional distress, family psychosocial adjustment and risk management behavior,
and personalized preventive programs, following the PICO elements [
33
]. Boolean and
truncation operators were used to combine search terms more systematically and to list

Int. J. Environ. Res. Public Health 2022,19, 1603 3 of 22
documents containing variations on search terms, respectively [
34
]. We modified the search
syntax as appropriate for each database.
2.2. Inclusion and Exclusion Criteria
We only included articles that: (1) were original studies; (2) described the psychosocial
adjustment of the family system of pre-symptomatic pathogenic variant carriers to inherited
cancer risk test and/or personalized preventive programs; (3) investigated at least one
measure of psychological adjustment (e.g., emotional distress, quality of life, anxiety, de-
pression, anger) to genetic testing results or risk management behaviors of carrier’s family
members; (4) investigated family barriers and facilitators of decision making and adherence
to personalized preventive programs/risk management behaviors. Studies targeting fami-
lies of either mixed populations (affected/unaffected) or currently unaffected individuals
previously diagnosed with cancer were included. We did not restrict publications based on
the study design, ethnicity, or year of publication. We opted only to include studies on pre-
symptomatic pathogenic variant carriers to better capture the experience of being and living
with a pathogenic variant carrier, which may be different from that of being and living with
a hereditary cancer patient. The methodological choice of not restricting studies by design
methods aimed to aggregate all existing knowledge about the psychological adjustment of
families to inherited cancer risk. Articles were excluded if: (1) pre-symptomatic pathogenic
variants carriers were under the age of 18 years; (2) considered families were made up only
of individuals not yet tested for inherited cancer risk; (3) considered families of affected
(cancer patients) were solely pathogenic variant carriers; (4) only biomedical outcomes
were considered; (5) only the psychosocial adjustment of pre-symptomatic pathogenic
variant carriers was investigated, but not one of their family members.
2.3. Study Selection
Following the search and exclusion of duplicates, two reviewers (authors GP and
VB) independently screened the eligibility of the articles first by title and abstract, and the
full text according to the inclusion criteria. Authors CS and PMM resolved disagreements.
Authors PG and CS conducted a separate search by independently screening reference lists
of previous systematic reviews [
22
–
24
,
26
,
28
,
30
,
35
], one doctoral thesis [
36
], and searching
articles in relevant journals (e.g., American Journal of Human Genetics, European Journal of
Human Genetics, Journal of Genetic Counselling, Journal of Community Genetics, Health
Psychology, Psycho-Oncology). Search updates were conducted by author PG in 2020 and
by authors PG and MN in 2021. Following Smith et al. [
37
], the review team included at
least one person with methodological expertise in conducting systematic reviews (PG, GP,
VB, CS, PMM) and at least two experts on the topic under review (CS, ES, EC, JS).
Searches of electronic databases identified 1338 reports, and searches by hand identi-
fied 16 articles. From the 1354 total records found, 21 were duplicates, and 1286 records
were excluded based on information from the title and abstract. The remaining 47 articles
were evaluated for inclusion by reviewing their full text and resulted in the exclusion of
17 records for the following reasons: (1) considered only the psychosocial adjustment of
unaffected pathogenic variant carriers, but not of their families (n= 8) [
38
–
45
]; (2) consid-
ered the psychological adjustment of families of individuals not yet tested for inherited
cancer risk; (n= 1) [
46
]; (3) did not report quantitative/qualitative outcomes (e.g., opinion,
theoretical, perspective articles, etc.) (n= 5) [
47
–
51
]; (4) pre-symptomatic pathogenic vari-
ant carriers were under the age of 18 (n= 1) [
52
]; (5) study focuses more on the carrier’s
type of communication than on the psychological impact of the genetic test results on
their family/system (n= 2) [
53
,
54
]. During the search update, three new articles were
included [
55
–
57
]. References of the remaining 30 articles were further screened for relevant
records, but none was found. The flowchart presented in Figure 1provides step-by-step
details of the study selection process.

Int. J. Environ. Res. Public Health 2022,19, 1603 4 of 22
Int. J. Environ. Res. Public Health 2022, 19, x FOR PEER REVIEW 4 of 21
theoretical, perspective articles, etc.) (n = 5) [47–51]; (4) pre-symptomatic pathogenic vari-
ant carriers were under the age of 18 (n = 1) [52]; (5) study focuses more on the carrier's
type of communication than on the psychological impact of the genetic test results on their
family/system (n = 2) [53,54]. During the search update, three new articles were included
[55–57]. References of the remaining 30 articles were further screened for relevant records,
but none was found. The flowchart presented in Figure 1 provides step-by-step details of
the study selection process.
Figure 1. PRISMA Flow-chart.
2.4. Assessment of Risk of Bias
The mixed-methods appraisal tool (MMAT-v2018) [58] was used to assess the meth-
odological quality of each selected study. The MMAT-v2018 includes a total of 25 criteria
and two screening questions rated on a scale of yes, no, and cannot tell. The tool results in
Figure 1. PRISMA Flow-chart.
2.4. Assessment of Risk of Bias
The mixed-methods appraisal tool (MMAT-v2018) [
58
] was used to assess the method-
ological quality of each selected study. The MMAT-v2018 includes a total of 25 criteria and
two screening questions rated on a scale of yes, no, and cannot tell. The tool results in a
methodological rating of 0 (0% lowest quality) to 5 (100%, highest quality) quality criteria
met by each study [
58
]. The assessment was conducted independently by authors VB and
GP, and any disagreements were resolved by a third author (PG, PMM, or CS). The ratings
of each selected study are presented in Supplementary material 1 (Table S1).
2.5. Data Extraction and Synthesis
Authors GP and VB independently extracted the following data from included stud-
ies: first author and year of publication; country; aim of the study; study design; study
setting; study outcome; follow-up points, sample size, age of applicants; gender of the
applicants; clinical status of the family member; the role of the member in the family; the
family role of the pathogenic variant carriers; type of pathogenic variant/cancer; psycho-
logical/behavioral outcome(s) and measure; results; retention; barriers and facilitators. The

Int. J. Environ. Res. Public Health 2022,19, 1603 5 of 22
results of selected studies were summarized to provide a qualitative synthesis of the impact
that genetic risk test positive results and risk management decisions have on the family
psychosocial adjustment, and how the family influences the psychological response and
risk management behaviors of both the pre-symptomatic pathogenic variant carrier and
family members themselves.
3. Results
3.1. Description of the Included Studies: The MMAT-v2018 Checklist
The distribution of MMAT-v2018 scores was generally high across study designs,
with 22 out of 30 (73.3%) studies meeting 100% of quality criteria and eight records
having 80% of quality criteria met (see Supplementary Table S1). All qualitative stud-
ies (n= 5)
[14,56,59–61]
obtained the highest possible score, which was also achieved in
3 out of 7 (42.9%) quantitative non-randomized studies [
62
–
64
] and 13 out of 17 (76.5%)
records adopting a quantitative descriptive method [
55
,
65
–
76
]. One mixed-method study
of the two included in this review (50%) also met 100% of the quality criteria [
77
]. No
quantitative randomized controlled trial was included.
3.2. Overview of Characteristics of Included Articles
We identified 30 studies meeting inclusion criteria. Most of them (n= 17) were con-
ducted in the USA, while five studies were carried out in the Netherlands [
62
,
65
,
66
,
71
,
78
],
two in Canada [
67
,
79
], two in Australia [
66
,
68
], one in the United Kingdom [
69
], one in
Portugal [
56
], one in France [
57
], and another one in Japan [
63
]. Twenty-one records fo-
cused only on hereditary breast and ovarian cancer syndrome (HBOC); three focused on
hereditary non-polyposis colorectal cancer syndrome (HNPCC) [
59
,
63
,
80
]; three studies
comprised a sample of both HBOC and HNPCC pathogenic variant carriers [
65
,
66
,
81
]; one
study included HNPCC, HBOC, and hereditary diffuse gastric cancer syndrome (HDGC)
pathogenic variant carriers [
56
]; and one study regarded Familial Adenomatous Polypo-
sis [
71
]. The sample size varied from a minimum of 17 participants (cumulative between
pathogenic variant carriers and their family members) [
79
] to a maximum of 272 pathogenic
variant carriers, only [
65
,
66
]. Carriers were all adults in the age range of 20–50. Most studies
investigated the experience of genetic testing in couple and sibling relationships. When
referring to psychological adjustment, studies considered a variety of constructs, such as
general and cancer-related distress, cancer worry, risk perception, depression, anxiety, and
somatization. Most papers presented pre- post-testing studies conducted with pathogenic
variant carriers, with post-testing typically measured six months after testing results. How-
ever, one study measured long-term adjustment of up to 24 months after receiving genetic
testing results [
72
]. Five papers employed a qualitative research method conducted on
pathogenic variant carriers and their family members [
14
,
56
,
59
–
61
]. A summary of the char-
acteristics of selected studies can be found in Table 1, while a more complete description of
selected records can be consulted in Supplementary Table S2.

Int. J. Environ. Res. Public Health 2022,19, 1603 6 of 22
Table 1. Characteristics of the included studies (summarized).
Author, Year Design GT Sample Size (n)Gender|MALE-
n(%):FEMALE-n(%) Main Outcomes
Ashida et al.,
2009 [70]Longitudinal cohort study HBOC 178 75(42.1%):103(57.9%)
Lower perceived family cohesion associated with
higher depression scores; Increase in family conflict
associated with lower depression scores in families
with higher levels of cancer worry.
Bartle-Haring et al.,
2003 [81]
Longitudinal observational
(pilot) study HBOC or HNPCC 50:MC = 25; FM = 25 MC = 5(20%):19(76%);
FM = 9(36%):14(56%)
Higher levels of differentiation of self are associated
with less distress in mutation carriers and
family members.
den Heijer et al.,
2011 [62]Longitudinal observational HBOC 222 F = 100%
Open communication within families is associated
with less breast cancer-specific distress and plays a
mediating role between social support and distress.
Di Prospero et al.,
2001 [79]Exploratory study HBOC 24 2(8.3%):22(91.7%)
Most participants felt a little or moderately worried
about cancer risk, and nine subjects considered they
would benefit from a support group.
Douma et al.,
2011 [71]Cross-sectional FAP FM = 129 63(49%):65(51%)
30% of partners reported moderate to severe levels
of distress; Partners ‘distres significantly associated
with carriers’.
Eliezer et al.,
2014 [80]Longitudinal observational HNPCC 179 (26 families) 75(42%):104(58%)
A higher proportion of carriers in the family
predicted a higher probability of participants
presenting clinical levels of depression
Hamann et al.,
2008 [74]Experimental HBOC
98 (49 dyads: 16 positive,
13 negative,
20 mixed results)
23(23.5%):75(76.5%)
Dyads with mixed results (one positive, one
negative) reported less friendly support behavior
and a higher increase in anger than dyads with
positive or negative results.
Katapodi et al.,
2011 [55]
Descriptive,
Cross-sectional HBOC 372 (MC = 200; FM = 172) F = 100%
Probands showed higher risk perception and more
distress than their relatives; Relatives showed a
higher perception of severity and controllability.
Koehly et al.,
2008 [73]Cross-sectional HBOC 65 (31 families) F = 100%
Significant within family correlation of perceived
risk, cancer worry, anxiety, and somatization
irrespective of mutation status.

Int. J. Environ. Res. Public Health 2022,19, 1603 7 of 22
Table 1. Cont.
Author, Year Design GT Sample Size (n)Gender|MALE-
n(%):FEMALE-n(%) Main Outcomes
Lodder et al.,
2001 [78]Longitudinal observational HBOC 154 (MC = 78 FM = 56) F = 100%
Higher anxiety levels were found in 20% of carriers
and 35% of partners. Levels of anxiety best
predicted by pre-test level of anxiety.
Manne et al.,
2004 [82]Longitudinal observational HBOC 464 (MC = 212; FM = 252) MC_F = 100%;
FM = 117(99.2%):1(0.8%)
Less partner support and more protective buffering
from partner before the test predicted more distress
from carriers 6 months after results; Partners who
felt understood by applicants at baseline reported
less distress 6 months after.
Mauer et al.,
2015 [83]Cross-sectional HBOC FM = 25
Participants reported negative changes in intimacy
levels, attraction, and communication with their
partners and more frequent discussions about
the future.
Mays et al.,
2014 [76]Prospective study HBOC 109 dyads FM_Mothers: F = 100%;
FM_Partners: M = 100%
Decisional conflicts before genetic testing from one
member of the couple predicted higher distress in
the other member of the dyad one month after
the test.
McInerney-Leo
et al.,
2005 [84]
Prospective study HBOC 262 Total = 92(35%):170(65%)
Perceptions of family cohesion increased both when
participants underwent testing and when they did
not; Conflict decreased from baseline for those who
underwent testing.
Mendes & Sousa,
2012 [56]
Exploratory, qualitative
study
HNPCC or HBOC
or HDGC 50 (9 families) F = 58%
Cancer related events within the family impact how
carriers assess their risk; Families consider genetic
counseling an emotionally taxing process.
Metcalfe et al.,
2002 [67]Cross-sectional HBOC FM = 59 M = 100%
Twenty percent of partners considered their carrier
spouse received inadequate support. Most partners
felt that the syndrome brought them closer to
their spouse
Milhabet et al.,
2013 [57]Cross-sectional HBOC FM = 77 F = 100%
Overscreening behaviors by non-carriers were
associated with feelings of self-vulnerability and
pessimism related to cancer risk

Int. J. Environ. Res. Public Health 2022,19, 1603 8 of 22
Table 1. Cont.
Author, Year Design GT Sample Size (n)Gender|MALE-
n(%):FEMALE-n(%) Main Outcomes
Mireskandari et al.,
2006 [61]Exploratory study HBOC FM = 15 M = 100%
Better adjustment and coping for partners of
women with HBOC were associated with dealing
with the stressor as a team, involvement in the
decision-making, satisfaction with supportive role,
and optimism.
Mireskandari et al.,
2007 [68]
Single-assessment study
design HBOC 190 (MC = 95; FM = 95 95(50%):95(50%)
Clinical levels of distress were reported by 10% of
partners of women at high risk of HBOC; Open
communication within the couple associated with
less partner distress.
Murakami et al.,
2004 [63]
Prospective qualitative
study HNPCC 47 (MC = 31; FM = 16) Total = 20(47.6%):22(52.4%)
Some carriers reported feelings of guilt either
towards their children or family members affected
by cancer.
Norris et al.,
2009 [60]
Descriptive qualitative
study HBOC 17 (5 families) 6(35.3%):11(64.7%)
Families often need more professional support than
what they are getting with genetic counseling.
Parents are unsure about how to share genetic
information with their offspring.
Patenaude et al.,
2013 [77]
Observational
mixed-methods study HBOC MC = 40 F = 100%
Daughters presented worries about their own risk
and their mothers’, and 32% percent of participants
showed clinical levels of cancer-risk distress.
Peterson et al.,
2003 [59]
Retrospective qualitative
study HNPCC 39 (5 families) 15(38.5%):24(61.5%)
Spouses of carriers considered the news about the
mutation as less personally relevant even when they
had children at risk. Members of families with the
most uptake of genetic testing worried for others
that opted not to be tested
Puski et al.,
2018 [14]Qualitative descriptive HBOC 20 F = 100%
Most often, family members are involved in the
decision-making process by providing emotional
and social support; Some family members may put
too much pressure on carriers to make a decision,
causing them discomfort.

Int. J. Environ. Res. Public Health 2022,19, 1603 9 of 22
Table 1. Cont.
Author, Year Design GT Sample Size (n)Gender|MALE-
n(%):FEMALE-n(%) Main Outcomes
Shapira et al.,
2017 [64]Observational HBOC 229 (MC = 168; FM = 61) NR
Partner’s perception of risk similar to carriers’.
Dyadic coping scores not related to carriers’ or
partners’ adaptation scores
Smith et al.,
1999 [75]Longitudinal observational HBOC 212 87(41%):125(59%)
Non-carrier men whose siblings tested positive
reported more distress than when siblings tested
negative; Carrier women whose siblings either
tested negative or had not yet been tested presented
greater psychological distress.
Van Oostrom et al.,
2007a [65]Prospective study HNPCC and HBOC MC = 271 32(12%):239(88%)
Participants perceiving family functioning as
maladaptive reported more hereditary
cancer-related distress than participants who
perceived their family as adaptive.
Van Oostrom et al.,
2007b [66]Prospective study HNPCC and HBOC MC = 272 32(12%):239(88%)
Perceiving their family as enmeshed-chaotic or
disengaged and feeling less free to talk about
cancer-risk related issues predicted relationship
problems with their family.
Watts et al.,
2011 [69]Observational HBOC 188 (MC = 94; FM = 94) F = 100% (FM_M = 100%)
Higher perceived support associated with greater
dyadic consensus and satisfaction; Dyadic cohesion
and satisfaction were associated with the use of a
team approach when dealing with stressors
Wylie et al.,
2003 [72]Longitudinal observational HBOC 203 M = 100%
Higher anxiety from the partner predicts higher
distress for the tested person, while higher support
from the partner predicts lower distress for the
applicant.
Legend: NR = GT = Genetic test; HNPCC = Hereditary nonpolyposis colorectal cancer; HBOC = Hereditary breast and ovarian cancer syndrome; FM = family member; MC = pathogenic
variant carrier.

Int. J. Environ. Res. Public Health 2022,19, 1603 10 of 22
3.3. The Family System Facing Genetic Testing Results
Overall, family members experienced anguish, worry, and guilt after genetic testing
results throughout the selected studies. More specifically, partners of pathogenic variant
carriers reported psychological distress, anxiety [
68
,
71
,
76
,
77
], and worries about their
spouse developing cancer and dying, as well as concerns about their children carrying the
pathogenic variant [
67
]. Adult daughters of unaffected BRCA1/2 (a type of HBOC) carriers
showed clinical levels of cancer-related distress and worries both regarding their mothers
and other relatives [77].
Moreover, pathogenic variant carriers disclosed feeling guilty for their children and
their carrier siblings [
63
,
66
], while non-carrier HNPCC applicants declared feeling guilty
towards relatives with hereditary cancer [
63
]. Also, both carriers and non-carriers showed
worries about relatives who opted not to pursue genetic testing [
63
,
66
]. Untested women
potentially at risk of HBOC presented less psychological distress and decisional conflicts
when compared to their relatives who pursued genetic testing [
55
]. However, they were
also less knowledgeable about potential risk factors and gene inheritance, besides reporting
a greater perception of disease severity and controllability [55].
3.3.1. Positive and Negative Relational Changes after Genetic Testing
Applicants for HBOC and HNPCC reported feeling closer to their partners and siblings,
while communication, support, and appreciation also improved for the other relatives.
At the same time, applicants reported familial conflicts and difficult situations within the
family due to genetic testing [
66
]. A study comparing HBOC carriers and non-carriers found
that perceptions of family expressiveness (the extent that family members are encouraged
to act openly and express their feelings) decreased significantly more for carriers between
the first genetic counseling session and 9 months after results [
84
]. In contrast, perceptions
of family cohesion and family conflict did not differ significantly between pathogenic
variant carriers and non-carriers [
84
]. Interestingly, one study observed that in families
with HBOC and HNPCC, an increase in the levels of family conflict after genetic testing
predicted lower depression scores at 12 months [70].
Three reviewed studies indicate that pre-existing family functioning characteristics
are predictors of the psychological adjustment of applicants [
65
,
66
,
70
]. HNPCC applicants
who perceived lower family cohesion at pre-test, as well as a decrease in family cohesion
six months after receiving the results, had higher depression scores one year later [
70
].
Also, applicants who perceived their nuclear families as disengaged or enmeshed at pre-
test presented higher levels of hereditary cancer distress six months after test results [
65
].
They also experienced more adverse consequences in their relationships with partners and
children when compared to applicants who felt their families moderately cohesive and
adaptive [66].
The presence of the pathogenic variant in the extended family was also a predictor
of the psychological adjustment of newly discovered pathogenic variant carriers. A study
with 179 first and second-degree relatives of HNPCC pathogenic variant carriers found
that a higher number of carriers (both in the immediate and extended family) predicted
more depressive symptomatology in pathogenic variant carriers six months after the test
result [
80
]. Cancer-related worries also tended to rise with the increase in the number of
HNPCC carriers in the extended family, and cancer-related distress and worry were higher
when the proportion of carriers in the immediate family was low [
71
]. Discrepancies in
cancer worry (when applicants had significantly different results in cancer worry at pre-test
compared to the family norm) also predicted higher depression scores 12 months after
HNPCC results [70].
3.3.2. Siblings’ Adjustment
Four studies included in this review focused specifically on the adjustment dynamics
within sibships [
73
–
75
,
78
]. Smith et al. [
75
] assessed the psychological distress before and
after genetic testing for BRCA1/2 in 212 sibships tested simultaneously. Distress was higher

Int. J. Environ. Res. Public Health 2022,19, 1603 11 of 22
for both siblings when one sibling tested positive alone, and lower when results were
positive for more than one sibling. Moreover, non-carrier siblings felt more distress when
their siblings were carriers than when all siblings were non-carriers [
75
]. The importance
of the pathogenic variant pattern among brothers and sisters was also discovered by
Hamann et al. [
74
], who concluded that siblings who both tested positive for BRCA1/2
reported more friendly behavior towards each other than when only one sibling did. Also,
Lodder et al. [
78
] found that non-carrier women who had a sister recently identified with
the BRCA 1/2 pathogenic variant presented higher levels of depression at post-test than
other non-carrier women. Furthermore, a study with 65 sisters of HBOC families found
that non-carriers experienced similar levels of perceived risk, cancer worry, anxiety, and
somatization as carriers [73].
3.3.3. Couples’ Adjustment
Eleven studies focused specifically on the adjustment process to test results regarding
couples [
59
,
61
,
64
,
66
–
69
,
71
,
72
,
82
,
83
]. Cross-over effects in the couple were observed. That
is, emotional states in one member of the couple were found to affect the adjustment of
the other. Partner’s distress was correlated with the level of distress reported by women at
risk of developing breast/ovarian cancer [
68
] and individuals with familial adenomatous
polyposis [
71
]. High levels of partner support reported by HBOC carriers before taking the
test significantly predicted lower levels of pathogenic variant carriers’ distress up to two
years after the test [
72
]. On the other hand, perceived partner anxiety predicted pathogenic
variant carrier distress in the same time frame [
72
]. Importantly, effect sizes were stronger
when pathogenic variant carriers perceived their partners as both unsupportive and anxious
before testing, which predicted clinical distress levels up to two years after testing [
72
].
In another study focusing on HBOC couples, applicants reported less general and cancer-
specific distress six months after test results when their partners had shared concerns and
had provided effective support before genetic testing [
82
]. Moreover, low perceived partner
support and the partner avoiding talking about worries to protect the partner (protective
buffering) predicted higher general distress in the applicant [
82
]. However, some applicants
actively avoid partner support. Oostrom et al. [
66
] found that some applicants react to a
positive pathogenic variant test by trying to emotionally distance themselves from their
partners to protect and prepare them for the possibility of developing cancer or dying for it.
Six studies reported on the impact of the pathogenic variant in the partner and the
couple’s relationship [59,61,67,68,82,83]. Partners of HBOC pathogenic variant carriers ex-
perienced genetic testing as a stressful situation and considered this new medical condition
exacerbated pre-existing couple relationship problems [
61
]. These partners indicated they
would need more support but did not search for it because they were focused on helping
their applicant spouses [
61
]. Some partners also mentioned discomfort about sharing wor-
ries with their spouses [
61
,
82
] because they did not want to overburden them. Therefore,
the couple did not share their preoccupations, which often led applicants to think their
partners were not sufficiently caring [
61
,
67
]. In this context, partners reported significant re-
lationship strain [
82
], less couple intimacy, more frequent discussions about the future [
83
],
and a sense of urgency regarding the pursuit of couples’ life goals [
61
]. In contrast, open
communication about cancer risk within the couple was found to be related to less distress
in partners of women at risk for developing breast/ovarian cancer [
68
]. Some BRCA 1/2
partners reported becoming more involved in their spouses’ families, talking more about
cancer risk with the pathogenic variant carrier [
83
], and feeling closer to their spouses
after genetic testing [
67
]. Also, some partners of HNPCC pathogenic variant carriers and
partners of not-yet-tested HNPCC individuals did not perceive their partners’ medical
condition as personally relevant, even if their children were also at risk of carrying the
pathogenic variant [59].
Findings from two studies suggest that approaching cancer risk as a team may ben-
efit the couple’s adjustment [
61
,
69
]. Study [
69
] found a significant positive association
between dyadic consensus (the extent to which couples agree on important matters for the

Int. J. Environ. Res. Public Health 2022,19, 1603 12 of 22
relationship) and levels of perceived support in couples dealing with HBOC risk. Higher
scores for support and team approach were also significantly associated with the couple’s
satisfaction69. Another study with HBOC families found that dealing with cancer risk
as a team facilitates psychological adjustment, along with more active participation from
partners in decision-making processes, greater satisfaction with their role as a supporter,
and optimism [
61
]. However, the positive effect of dealing with cancer risk as a team was
not confirmed by Shapira et al. [
64
], who did not find a significant association between
dyadic coping and psychological adaptation in women identified with the BRCA 1/2
pathogenic variant.
3.3.4. The Family System Facing Risk-Reduction Decision Making and Long-Term
Managing of Cancer Risk
Six studies [
14
,
56
,
59
,
60
,
62
,
64
] focused specifically on family participation in risk re-
duction decision-making processes and long-term adjustment to life with hereditary cancer
risk. A qualitative study with a heterogeneous hereditary cancer risk population found
that family members generally communicated during involvement in genetic counseling
and adopted open communication within the nuclear family and first-degree relatives
but reported more difficulty informing extended family relatives due to emotional dis-
tance [
56
]. Moreover, BRCA1/2 pathogenic variant carriers interviewed by Puski et al. [
14
]
reported that having witnessed family members’ experience of being diagnosed and treated
for HBOC represented a stimulus to be pro-active and to opt for risk-reducing surgery.
They considered it helpful to gain information about the surgical process, healing time,
and side effects from family members who had already undergone a mastectomy or an
oophorectomy [
14
]. The participants reported that while non-carrier relatives gave support
by validating decisions, pathogenic variant carriers provided camaraderie and instilled
hope and reassurance by sharing their experiences [
14
]. However, two participants reported
adverse effects concerning support given by relatives who either tried to persuade them to
undergo the surgical procedure when they did not want to or expressed disapproval when
they intended to do the surgery [14].
Two studies found that risk management decisions had a significant impact on the
process of adaptation to life with increased cancer risk, both for the pathogenic variant
carriers and for their partners [
62
,
64
]. Study [
64
] discovered that women who underwent
a risk-reducing mastectomy and their partners reported significantly higher levels of
psychological adaptation to BRCA1/2 than women who did not. Study [
62
] explored the
long-term psychological impact of either regular breast cancer surveillance or prophylactic
surgery and found that open communication within the nuclear family (partner and
children) and with the family of origin (parents and siblings) four to nine years after
genetic testing results were significantly associated with less breast-cancer-related distress
in BRCA 1/2 pathogenic variant carriers [
62
]. Open communication with family members
also significantly mediated the positive effect of social support on general and breast
cancer-specific distress. In other words, women who felt supported by their families were
more likely to talk openly about hereditary cancer with their close relatives (e.g., partner,
children, parents, and siblings), promoting their psychological adjustment [62].
Regarding the risk management of unaffected non-carriers, those that belong to
BRCA1/2 families report overscreening behaviors, even though these were not recom-
mended [
57
]. These overscreening behaviors correlated to a higher feeling of self-vulnerability
and higher comparative pessimism (e.g., tendency to think that negative events will more
likely happen to oneself than to others), but not to higher anxiety levels [57].
3.3.5. Parents and Children Facing Hereditary Cancer Risk
Three studies reported on the experience of being a parent in a family identified
with hereditary cancer syndromes [
60
,
76
,
77
]. Two of three studies focused on the impact
that poor communication might have on children of parents who are pathogenic variant
carriers [
60
,
76
]. A qualitative study [
60
] involving five families with HBOC showed that

Int. J. Environ. Res. Public Health 2022,19, 1603 13 of 22
parents found it difficult to talk with their children about cancer risk or downplayed
the importance of the information and postponed disclosing their status. Consequently,
children ended up learning about the familial cancer risk in an informal manner, without
really understanding its meaning and consequences [
60
]. Children’s inaccurate cancer
risk perception and poor health literacy were also found by Patenaude et al. [
77
]. Some
adult daughters of BRCA1/2 pathogenic variant carriers were unaware that they could be
at a higher risk for cancer because their mothers were pathogenic variant carriers. Also,
they did not know that if a woman carries the pathogenic variant, her sister has a 50%
probability of being a carrier, and they were unaware of the importance of undergoing
genetic testing to prevent cancer onset [
77
]. The parental influence on children’s future
health behavior was evident in HBOC families. It was observed that daughters made the
same choice their pathogenic variant carriers’ mothers did regarding both genetic testing
and risk management measures [60].
Difficulties in discussing cancer risk with their children also affected pathogenic
variant carriers significantly [
76
]. In a study by Mays et al. [
76
] poor parent-child com-
munication before genetic testing predicted greater distress in mothers one month after
receiving their HBOC test results [
76
]. Interdependent effects of parenting dynamics were
also reported in women at risk of HBOC and their partners. More specifically, high levels
of pre-test individual uncertainty for one parent regarding how to communicate test results
to children significantly predicted increased distress in the other member of the couple up
to one month after test results [76].
One study reported that some adult descendants of HBOC carriers viewed the like-
lihood of being a pathogenic variant carrier as an intense experience, eliciting internal
conflicts and emotional pain [
77
]. Although most daughters in this study did not perceive
themselves as less healthy because their mothers were carriers, others revealed deep fears
and concerns regarding the possibility of carrying the pathogenic variant. These included
worrying about their psychological health, pessimistic and paranoid thoughts, as well as
the fear of having to change life plans, regarding childbearing in particular. Moreover,
some daughters were worried about transmitting the pathogenic variant to their children or
not living long enough to see them grow up. Many expressed the intention of undergoing
genetic testing as soon as possible, but others refused to be tested; the majority expressed
ambivalence [77].
A summary of all the factors we found that affect adjustment to hereditary cancer
syndromes within the family system can be found in Figure 2.

Int. J. Environ. Res. Public Health 2022,19, 1603 14 of 22
Int. J. Environ. Res. Public Health 2022, 19, x FOR PEER REVIEW 13 of 21
Figure 2. Summary of the factors affecting family adjustment to hereditary cancer syndromes.
4. Discussion
This systematic review intended to synthesize how families with pathogenic variant
carriers unaffected by cancer adjust to genetic testing results and life-saving risk manage-
ment programs offered in the context of cancer genetic counseling. Taken together, the
findings reveal a complex panorama where the systemic nature of family adjustment is
evident. The diagnosis of a hereditary cancer syndrome in an unaffected individual works
Figure 2. Summary of the factors affecting family adjustment to hereditary cancer syndromes.
4. Discussion
This systematic review intended to synthesize how families with pathogenic variant
carriers unaffected by cancer adjust to genetic testing results and life-saving risk manage-
ment programs offered in the context of cancer genetic counseling. Taken together, the
findings reveal a complex panorama where the systemic nature of family adjustment is
evident. The diagnosis of a hereditary cancer syndrome in an unaffected individual works

Int. J. Environ. Res. Public Health 2022,19, 1603 15 of 22
as a collective stressor, affecting not only the applicant but also their family. As posited by
Daly [
20
], the hereditary cancer syndrome goes from generation to generation, impacting
each family member and the entire family because “a positive genetic test would challenge
the family identity” (p. 549). As such, family members who are carriers may experience
depression, anxiety, and distress due to the fear of developing cancer and dying from it,
as well as concerns about transmitting the pathogenic variant to their children. Moreover,
non-carrier relatives may feel guilty towards family members affected by a pathogenic
variant or cancer disease, thus experiencing a particular kind of “survivor guilt” [
85
]
(p. 321)
. Survivor guilt is a distressing experience, where individuals blame themselves
for being the ones to survive a life-threatening situation or disease where others perished
got injured, or critically ill [
85
]. It is common in trauma [
85
] and cancer survivors [
86
],
and it can be a threat to families’ well-being and systemic functioning as it may lead to
relational distancing. Nevertheless, a diagnosis of hereditary cancer syndrome can also
bring positive changes. Findings show that being a pathogenic variant carrier seems to
bring a particular sense of connection and togetherness with other carriers in the family,
possibly due to sharing similar distressing experiences [
87
]. This translates to relational
changes in several sub-systems. Some family members might experience greater closeness,
improved communication patterns, and supportive dynamics, while others face conflicts
and difficult situations [66].
Reviewed studies also highlighted that pathogenic variant carriers may adjust dif-
ferently to positive genetic testing results, depending on the history and presence of the
syndrome in the nuclear and extended family [
80
]. These findings are in line with the Fam-
ily Systems Illness model (FSI; [
19
]), which is increasingly applied in genomic disorders
as a theoretical framework for understanding family challenges. According to this model,
successful or dysfunctional family adaptation depends on the psychosocial demands of
the disorder and the family functioning and the resources used to cope with this stressor
by the family members. This family adaptation seems to be particularly important at the
level of close relationships, i.e., between siblings, partners, and children. Selected studies
provided evidence of better individual adjustment to the result of genetic testing when
siblings have the same results, even if they test positive. Furthermore, both carrier and
non-carrier siblings appear to experience similar levels of perceived risk, cancer worry,
anxiety, and somatization [
73
], revealing the adjustment processes to be interdependent.
Regarding the partners of pathogenic variant carriers, although some of them did not
consider the medical condition of their partners as personally relevant [
59
], others viewed
genetic testing as a stressful event that seemed to exacerbate previous problems in the
romantic relationship [
62
]. Some partners described their need for support. However, their
role as caregiver and support provider for their partner led them not to share their feelings
and concerns [
62
,
82
]. In addition, the couple faces a central distressing difficulty in sharing
genetic risk information with their children and in dealing with their reactions. For the
children, the likelihood of also being a pathogenic variant carrier appeared as an intense
experience they needed to adjust to [
77
]. To this end, children stressed the importance
of more accurate information about genetic risk and what it entails so they could make
informed decisions about their health and future life plans. This review also recognized
the parents’ difficulties and children’s need for information that led Werner -Lin et al. [
88
]
to develop a set of recommendations for healthcare professionals to facilitate parents’ de-
cisions and disclosure processes for their school-aged children, adolescents, and young
adults, according to their developmental abilities.
Family functioning and adjustment to a positive genetic test result and risk manage-
ment behaviors of a pathogenic variant carrier also influenced the psychological adjustment
and decision-making of new carriers. Some family dynamics (e.g., lower levels of family
cohesion, disengagement, enmeshment) before and after genetic testing were associated
with individuals’ depression [
70
], higher levels of cancer distress, and worse relationships
with partners and children [
65
] after receiving test results. The reviewed studies also
provided strong evidence for the impact of the partner’s adjustment on the pathogenic

Int. J. Environ. Res. Public Health 2022,19, 1603 16 of 22
variant carrier’s long-term fine-tuning to the hereditary cancer syndromes. For example,
communication about the syndrome was hindered when carriers felt their partners were
unsupportive, not involved, or not attuned to their suffering, and thus preferred to cope
with the stressful situation alone [
59
,
66
]. In contrast, open communication and approaching
cancer as a team was associated with better adjustment [
61
,
62
,
68
]. This is in line with a
previous review in which the interaction between couple members influences each other’s
distress [
30
] and in studies with couples facing cancer, where it is suggested that couples
may act as systems, not just as individuals [89].
Although the literature is scarce, our review suggests that pathogenic variant carriers
followed the example of their family members, deciding in terms of genetic testing and
risk-management options. Family members might positively influence individual decisions
and risk management behavior of those carrying a pathogenic variant, functioning as role
models, and through sharing first-hand experiences or as interlocutors thus support the
decision-making process. Testimonials and active encouragement from family members
might also provide valuable information to help potential applicants decide whether to
undergo genetic testing and other preventive measures [
14
,
90
]. Nevertheless, relatives
might also function as a source of biased information or contribute to additional distress
when they insist on trying to persuade pathogenic variant carriers to make certain decisions,
challenging their self-determination [14].
Support received from family members was recognized by both non-carriers and carri-
ers as important in dealing with the challenges posed by their condition. Emotional support
in families with hereditary cancer, in which multiple members simultaneously provide and
receive support from relatives, was characterized as a communal coping process [
73
,
91
],
as previously identified in individuals with other chronic conditions [
92
]. The positive
effect of family support on distress seems to be explained by open communication between
family members [
62
]. However, communication may be hindered by protective buffering
processes. Pathogenic variant carriers may refrain from sharing their concerns for fear of
aggravating the distress of their close relatives or may emotionally slip away from their
partners to help them better prepare for the eventuality of their death from cancer [
66
].
Indeed, this dimension has already been recognized in previous studies, leading to the
development of interventions specifically aimed to improve family communication about
hereditary cancer and genetic testing [93].
4.1. Limitations of the Current Research
Most of the selected studies focused on the psychological adjustment of families with
inherited hereditary breast and ovarian cancer risk and HNPCC risk. Only one study
explored the emotional response and role of the family in the decision-making process of
positive mutation carriers of other syndromes (Familial Adenomatous Polyposis). This may
reflect a gap in the literature on the topic, but also that our search entailed a syntax that
was not broad enough to encompass other hereditary cancer syndromes. Other medical
terms may have been used in studies relating to other hereditary cancer syndromes. Also,
not restricting studies by study design helped aggregate existing knowledge but prevented
a meta-analytical approach that could yield a more precise estimate of the strength of
the findings.
4.2. Research Gaps and Recommendations for Future Studies and Clinical Practice
Our review identified four major research gaps. First, there is scant knowledge about
the psychological adaptation of children growing up in families with a known hereditary
cancer syndrome. This calls for further research that explores how hereditary cancer affects
the psychological development and health behaviors of children and adolescents, and how
it should be managed to minimize negative impacts. A second major gap concerns the
lack of research focused on the long-term adjustment phases of risk management. Little is
known about how best to involve family members at critical turning points in risk-reduction
decision-making and their adjustment to the consequences of those decisions over time. In

Int. J. Environ. Res. Public Health 2022,19, 1603 17 of 22
this process, it is important to consider the limits and possible contraindications of family
involvement. Such knowledge is critical to empowering the family to use its resources for
mutual support.
A third gap concerns the lack of cancer genetic health literacy interventions for both
applicants and their relatives on the following topics: the multiple psychological impacts
of hereditary cancer risk on applicants, their biological relatives, and partners; the expected
impact on relationships and how to overcome it; the importance of family self-supportive
dynamics (e.g., open communication), and the common difficulties associated with it (e.g.,
protective buffering, survivor guilt). Health literacy targeting close relatives from whom
the carrier expects support, such as partners, might be more important in families without
a clinical history of familial cancer, given the possible devaluation of the syndrome and
the carrier’s distress. Fourth and lastly, there is a lack of translational research towards
family-centered genetic cancer risk care. The reviewed role of the family in the individ-
ual adjustment of pathogenic variant carriers calls for a debate about balancing the right
to self-determination and individual privacy (e.g., the right not to involve the family in
decision-making processes) with family-centered interventions. Hereditary cancer syn-
drome is a clinical condition in which several members of the same family are at different
stages of diagnosis/risk management through interdependent adjustment processes and
communal coping. Thus, interventions that target the family system and not just its mem-
bers individually should be considered, to better address the family’s psychosocial and
clinical needs. The few existing interventions, for example, Multifamily Discussion Groups
(MFDG) [
21
], have shown promising preliminary evidence regarding improving family
relationships and psychological well-being.
Research should further focus on the multiple interrelated adjustment processes [
15
]
to better capture the systemic nature of family adaptation. To this end, we provide four
methodological recommendations. First, to include family members as informants. Most
studies have used the applicant as the only data source, but it is important to examine
the lived experience of family members, especially children and young people. Second,
to examine the process of interdependent adjustment of family members (e.g., couples,
siblings, parents-children sub-systems) through dyadic or triadic study designs. Third, use
of longitudinal designs to examine family dynamics and adjustment trajectories. Studies
should consider the major family events expected in the course of hereditary cancer syn-
dromes: including the pathogenic variant carrier or a family member developing cancer;
the pathogenic variant carrier or a family member undergoing prophylactic surgery; the
pathogenic variant carrier reaching a critical age (e.g., the age at which the index case
was diagnosed with cancer); the pathogenic variant carrier becoming a parent; a child
of the pathogenic variant carrier reaching a critical age (e.g., the age at which they must
decide whether or not to be tested); or the death of a family member diagnosed with cancer.
Fourth, the active involvement of pathogenic variant carriers and their families in research
using participatory approaches would ensure that research focuses on topics relevant to
patients and close to their daily experiences. Moreover, this may contribute not only to
informing health professionals and improving care practices but also to increasing people’s
participation and adherence to treatment.
5. Conclusions
To our knowledge, our review is the first to describe family member adjustments to
genetic testing and risk management, and its influence on the psychological response and
risk management decisions and behaviors of pathogenic variant carriers. Our findings
provide valuable evidence regarding the interdependent adjustment processes of family
members to the increased risk of developing cancer. Three family members emerged as
particularly important for adult pathogenic variant carriers’ coping with the inherited
genetic pathogenic variant: siblings, romantic partners, and children. In fact, hereditary
cancer syndrome is a familial health condition, and a positive genetic testing result in a
person might have implications for their close and extended relatives. Their relationships

Int. J. Environ. Res. Public Health 2022,19, 1603 18 of 22
change, and pre-existing family functioning may affect not only the adjustment of the
newly diagnosed pathogenic variant carrier over time but may also subsequently affect
the adherence to genetic testing and the health behavior of other relatives. It is therefore
important to educate and support healthcare professionals in identifying key strengths and
weaknesses in individual and family adjustments for the provision of family-centered care.
Supplementary Materials:
The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/ijerph19031603/s1. The supplemental data includes two tables:
Supplementary Table S1—Evaluation of quality of selected records according to the mixed-methods
appraisal tool checklist (MMAT-v2018) and Supplementary Table S2—Detailed characteristics of the
included studies.
Author Contributions:
C.M.D.S., P.M.M. and G.P. conceptualized the study. G.P. and V.B. conducted
the first systematic searches in electronic databases. P.G. and C.M.D.S. conducted the hand searches,
and P.G. and M.C.N. conducted the search update in electronic databases. P.G., G.P., V.B., E.S., M.C.N.
and C.M.D.S. collaborated in selecting papers, quality appraisal, and extraction data. P.G., G.P.
and C.M.D.S. wrote the original draft. E.R.S., J.S., P.M.M., M.E.C., E.S. and C.M.D.S. reviewed the
manuscript and offered improvement suggestions. All authors have read and agreed to the published
version of the manuscript.
Funding:
This work was supported by the European COMPETE2020 under grant POCI-01-0145-
FEDER-030980, Portuguese National funds FCT-Fundação para a Ciência e a Tecnologia, I.P, under
grants PTDC/PSI-ESP/30980/2017, UIDB/00050/2020 to the CPUP -Center for Psychology at Uni-
versity of Porto, and the PhD scholarship 2020.07774.BD, as well as the COST (European Cooperation
in Science and Technology), under grant COST Action CA16102.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
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