PRESYMPTOMATIC TESTING FOR FAMILIAL CANCER SYNDROMES IN YOUNG ADULTS: CONSIDERATIONS, DECISION MAKING AND IMPACT

Godino L, Turchetti D, Jackson L, Hennessy C, Skirton H. (2016) Impact of presymptomatic genetic testing on young adults: a systematic review. European Journal of Human Genetics. 24:496-503. doi: 10.1038/ejhg.2015.153. E-pub 2015.Background: Presymptomatic genetic testing should always involve a considered choice. Young adults are at a key life stage as they may be developing a career, forming partnerships and potentially becoming parents. Presymptomatic testing may therefore affect the future lives of consultands significantly when testing is undertaken in early adulthood. Aim: To explore presymptomatic testing for hereditary cancer in consultands aged 18-30 years with particular reference to psychosocial impact, the decision-making process and the consequent counselling needs. Methods: A mixed-methods sequential exploratory design was used, comprising a systematic review, a qualitative study and a quantitative study. Results of all phases were used to build a theoretical model regarding the process of presymptomatic testing in young adults. Findings: The systematic review indicated that many participants grew-up with little or no information concerning their genetic risk. The experience of genetic counselling was either reported as an opportunity for discussing problems or associated with feelings of disempowerment. Parents appeared to have exerted pressure on their children during the decision-making process. However, as a result of the qualitative study, the influence of other people and the decision-making process prior to counselling were identified as key factors. Further results from the quantitative phase underlined that parents felt they had control over the decisions their children made, while the majority of the young adults reported the request for the genetic test as their own decision. A new theoretical model of decision making and impact on young adults was built to synthesise the overarching experience of participants in this research project. Conclusion: Counselling approaches to this population may require modification both for young adults and their parents. Young adults may benefit from a multi-step approach to presymptomatic testing. Parents need to be more informed that genetic counselling is a forum where information can be obtained and young adults can talk about the testing decision, regardless of whether they want to be tested or not. The traditional ‘wait until they come to us’ approach by health services may be failing to meet the educational and emotional needs of this population

Development and Validation of an Italian Adaptation of the Psychosocial Aspects of Hereditary Cancer Questionnaire

Individuals that attend cancer genetic counseling may experience test-related psychosocial problems that deserve clinical attention. In order to provide a reliable and valid first-line screening tool for these issues, Eijzenga and coworkers developed the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire. The aim of this work was to develop an Italian adaptation of the PAHC (I-PACH). This prospective multicenter observational study included three stages: (1) development of a provisional version of the I-PAHC; (2) pilot studies aimed at testing item readability and revising the questionnaire; and (3) a main study aimed at testing the reliability and validity of the final version of the I-PAHC with the administration of a battery comprising measures of depression, anxiety, worry, stress, and life problems to 271 counselees from four cancer genetic clinics. Adapting the original PAHC to the Italian context involved adding two further domains and expanding the emotions domain to include positive emotions. While most of the items were found to be easy to understand and score, some required revision to improve comprehensibility; others were considered irrelevant or redundant and therefore deleted. The final version showed adequate reliability and validity. The I-PAHC provides comprehensive content coverage of cancer genetic-specific psychosocial problems, is well accepted by counselees, and can be considered a sound assessment tool for psychosocial issues related to cancer genetic counseling and risk assessment in Italy

An analysis of clinical, surgical, pathological and molecular characteristics of endometrial cancer according to mismatch repair status. A multidisciplinary approach

Since 2016, our hospital has applied tumor testing with immunohistochemistry (IHC) in endometrial cancer in order to detect mutations of mismatch repair genes (MMR). All cases with MMR deficiency proteins expression are sent for genetic testing, except those with MLH1 protein deficiency, in which case genetic testing is performed if negative for promoter hypermethylation. The primary aim of this study was to investigate the ability of our algorithm to identify Lynch syndrome (LS). The Secondary aims were to investigate the relationship between MMR status and clinicopathological features and prognosis of primary endometrial cancer (EC). From January 2016 to December 2018, 239 patients with EC were retrospectively analyzed and subdivided according to MMR status. Patients were divided in three groups: MMR proficient, LS and Lynch-like cancer (LLC). LS was characterized by a lower age and BMI, more use of contraceptive and less use of hormonal replacement therapy, nulliparity and a trend versus a better prognosis. LLC appeared more related to MMR proficient than LS and exhibited a more aggressive behavior. Our multidisciplinary approach permitted a correct diagnosis of germline mutation in patients with newly diagnosis EC and it confirmed clinicopathologic and prognostic characteristics of LS

Efficacy of very low-calorie ketogenic diet with the Pronokal® method in obese women with polycystic ovary syndrome: a 16-week randomized controlled trial

Objective: The aim of this study isto assess the efficacy of a very low-calorie ketogenic diet (VLCKD) method vs a Mediterranean low-calorie diet (LCD) in obese polycystic ovary syndrome (PCOS) women of a reproductive age.Design: Randomized controlled open-label trial was performed in this study. The treatment period was 16 weeks; VLCKD for 8 weeks then LCD for 8 weeks, according to the Pronokal (R) method (experimental group; n = 15) vs Mediterranean LCD for 16 weeks (control group; n = 15). Ovulation monitoring was carried out at baseline and after 16 weeks, while a clinical exam, bioelectrical impedance analysis (BIA), anthropometry, and biochemical analyses were performed at baseline, at week 8, and at week 16.Results: BMI decreased significantly in both groups and to a major extent in the experimental group (-13.7% vs -5.1%, P = 0.0003). Significant differences between the experimental and the control groups were also observed in the reduction of waist circumference (-11.4% vs -2.9%), BIA-measured body fat (-24.0% vs -8.1%), and free testosterone (-30.4% vs -12.6%) after 16 weeks (P = 0.0008, P = 0.0176, and P = 0.0009, respectively). Homeostatic model assessment for insulin resistance significantly decreased only in the experimental group (P = 0.0238) but without significant differences with respect to the control group (-23% vs -13.2%, P > 0.05). At baseline, 38.5% of participants in the experimental group and 14.3% of participants in the control group had ovulation, which increased to 84.6% (P = 0.031) and 35.7% (P > 0.05) at the end of the study, respectively.Conclusion: In obese PCOS patients, 16 weeks of VLCKD protocol with the Pronokal (R) method was more effective than Mediterranean LCD in reducing total and visceral fat, and in ameliorating hyperandrogenism and ovulatory dysfunction.Significance statements: To the best of our knowledge, this is the first randomized controlled trial on the use of the VLCKD method in obese PCOS. It demonstrates the superiority of VLCKD with respect to Mediterranean LCD in reducing BMI with an almost selective reduction of fat mass and a unique effect of VLCKD in reducing visceral adiposity, insulin resistance, and in increasing SHBG with a consequent reduction of free testosterone. Interestingly, this study also demonstrates the superiority of the VLCKD protocol in improving ovulation, whose occurrence increased by 46.1% in the group treated by the VLCKD method against a rise of 21.4% in the group treated by Mediterranean LCD. This study extends the therapeutic approach possibilities in obese PCOS women

Characterization of BRCA Deficiency in Ovarian Cancer

BRCA testing is recommended in all Ovarian Cancer (OC) patients, but the optimal approach is debated. The landscape of BRCA alterations was explored in 30 consecutive OC patients: 6 (20.0%) carried germline pathogenic variants, 1 (3.3%) a somatic mutation of BRCA2, 2 (6.7%) unclassified germline variants in BRCA1, and 5 (16.7%) hypermethylation of the BRCA1 promoter. Overall, 12 patients (40.0%) showed BRCA deficit (BD), due to inactivation of both alleles of either BRCA1 or BRCA2, while 18 (60.0%) had undetected/unclear BRCA deficit (BU). Regarding sequence changes, analysis performed on Formalin-Fixed-Paraffin-Embedded tissue through a validated diagnostic protocol showed 100% accuracy, compared with 96.3% for Snap-Frozen tissue and 77.8% for the pre-diagnostic Formalin-Fixed-Paraffin-Embedded protocol. BD tumors, compared to BU, showed a significantly higher rate of small genomic rearrangements. After a median follow-up of 60.3 months, the mean PFS was 54.9 ± 27.2 months in BD patients and 34.6 ± 26.7 months in BU patients (p = 0.055). The analysis of other cancer genes in BU patients identified a carrier of a pathogenic germline variant in RAD51C. Thus, BRCA sequencing alone may miss tumors potentially responsive to specific treatments (due to BRCA1 promoter methylation or mutations in other genes) while unvalidated FFPE approaches may yield false-positive results

Presymptomatic genetic testing for hereditary cancer in young adults: a survey of young adults and parents

Presymptomatic testing for hereditary cancer syndromes should involve a considered choice. This may be particularly challenging when testing is undertaken in early adulthood. With the aim of exploring the psychosocial implications of presymptomatic testing for hereditary cancer in young adults and their parents, a cross-sectional survey was designed. Two questionnaires were developed (one for young adults who had considered presymptomatic testing, one for parents). Questionnaires were completed by 152 (65.2%) young adults and 42 (73.7%) parents. Data were analysed using descriptive statistics, inferential testing, and exploratory factor analysis and linear regression analysis. Young adults were told about their potential genetic risk at a mean age of 20 years; in most cases, information was given by a parent, often in an unplanned conversation. Although testing requests were usually made by young adults, the majority of parents felt they had control over the young adult’s decision and all felt their children should be tested. Results suggest that some young adults did not understand the implications of the genetic test but complied with parental pressure. Counselling approaches for presymptomatic testing may require modification both for young adults and their parents. Those offering testing need to be aware of the complex pressures that young adults can experience, which can influence their autonomous choices. It is therefore important to emphasise to both parents and young adults that, although testing can bring benefits in terms of surveillance and prevention, young adults have a choice

Decision making and experiences of young adults undergoing presymptomatic genetic testing for familial cancer: A longitudinal grounded theory study

Enabling informed choice is an essential component of care when offering young adults presymptomatic testing for a genetic condition. A systematic review on this topic revealed that many young adults grew up with little information regarding their genetic risk and that parents had applied pressure to them during the testing decision-making process. However, none of the studies retrieved were conducted in South European countries. To address this gap, we undertook a qualitative study based on grounded theory to explore the psychosocial implications of presymptomatic testing for hereditary cancer in Italian young adults aged 18-30 years. Interviews were conducted on three occasions: 1 month before counselling, and 2 weeks and 6 months after results. Data were coded and grouped under themes. A total of 42 interviews were conducted. Four themes emerged: knowledge, genetic counselling process, decision making and dealing with test results. Although participants grew up with little or no information about their genetic risk, none expressed regret at having the test at a young age. Pre-test counselling was appreciated as a source of information, rather than support for decision making. Decisions were often made autonomously and sometimes conflicted with parents' wishes. Participants reported no changes in health behaviours after testing. This evidence highlights the need for a comprehensive, longitudinal counselling process with appropriate timing and setting, which supports 'parent-to-offspring' risk communication first and decision making by young adults about presymptomatic testing and risk management afterwards. In conclusion, it is clear that counselling approaches for presymptomatic testing may require modification both for young adults and their parents. © 2017 European Society of Human Genetics

The Gen-Equip Project: evaluation and impact of genetics e-learning resources for primary care in six European languages.

To access publisher's full text version of this article click on the hyperlink belowGenetic advances mean patients at risk of genetic conditions can be helped through testing, clinical screening, and preventive treatment, but they must first be identified to benefit. Ensuring quality of genetic care for patients requires genetic expertise in all health services, including primary care. To address an educational shortfall, a series of e-learning resources was developed in six languages to equip primary care professionals with genetic skills relevant for practice. The purpose of the study was to evaluate these resources using Kirkpatrick's framework for educational outcomes. Mixed methods (qualitative and quantitative) were used over four phases of the study. A high level of satisfaction with the resources was reported. Knowledge and skills improved significantly after using the education material. Participants reported changes in confidence and practice behavior, including family history taking, seeking advice from specialists and referring patients. The resources helped users to learn how to explain genetics. Many visited the resources repeatedly and some used them to educate colleagues or students. Gen-Equip modules are effective in improving genetic knowledge, skills, and attitudes for primary care professionals. They provide both continuing professional development and just-in-time learning for a potentially large global audience at a practical level.European Unio

A systematic review of factors influencing uptake of invasive fetal genetic testing by pregnant women of advanced maternal age

Women of advanced maternal age have a higher risk of having a child affected by a chromosomal disorder than younger childbearing women and are frequently offered invasive testing during pregnancy. The aim of our systematic review was to identify and analyse the current evidence base regarding factors that influence the uptake of invasive fetal testing by pregnant women of advanced maternal age. We conducted a systematic review. A search of The Cochrane Library, CINAHL, Embase and Medline databases was undertaken for papers published in English and Italian from January 2002 to May 2012. Eleven studies satisfied the inclusion criteria, were subjected to quality assessment and included in the review. We analysed the data using thematic analysis. The factors influencing women were classified as either external or psychosocial factors. External factors included the opportunity for screening, screening results and use of genetic counselling. Psychosocial factors related to ethnicity, socio-demographic status and attendance of partners during counselling. It is difficult to draw firm conclusions as to the principle factors that influence uptake of invasive tests by women of AMA. More research is needed to enhance understanding of relevant factors to ensure that services are offered in a way that acknowledges practical as well as psychosocial influences. This type of research will help to equip midwives and other professionals caring for women during pregnancy to ensure that women are supported to make the choices that are appropriate for them and their families