Descriptive study on subjective experience of genetic testing with respect to relationship, family planning and psychosocial wellbeing among women with lynch syndrome

Background Due to increased risk of endometrial and ovarian cancer, women belonging to known Lynch Syndrome (LS) families are recommended to undergo germline testing. Current practice in Finland is to offer counselling to women with pathogenic variant and advocate risk-reducing surgery (RRS) after completion of childbirth. The present study aimed to clarify the impacts of positive germline testing on family planning and reproductive decisions of these women, which are relatively unknown. Methods Seventy-nine carriers of germline MMR gene pathogenic variant (path_MMR) were identified from the Finnish LS Registry as having genetic testing performed before the age of 45 years and not having undergone hysterectomy or oophorectomy. These women were sent a questionnaire concerning family planning, intimate relationships and psychosocial wellbeing. Results Thirty-five women (44.3%) responded. Parity of path_MMR carriers (2.1) was slightly higher than parity among Finnish women in general (1.8). No significant differences were found between parity, number of induced abortions or sterilizations before and after genetic testing. Only minority of subjects reported any influence on family planning (20%) or negative impact on feminine self and body image (14%). Conclusions The positive germline testing does not seem to have a major negative impact on family planning, intimate relationships or feminine self and body image. According to the open comments, counselling, supportive and empathic attitude of the professionals seem to have a significant impact on this. These results are a valuable addition to the counselling of LS women at reproductive age.Peer reviewe

Factors associated with decision-making on prophylactic hysterectomy and attitudes towards gynecological surveillance among women with Lynch syndrome (LS) : a descriptive study

To prevent endometrial carcinoma in Lynch syndrome (LS), regular gynecological surveillance visits and prophylactic surgery are recommended. Previous data have shown that prophylactic hysterectomy is an effective means of cancer prevention, while the advantages and disadvantages of surveillance are somewhat unclear. We aimed to evaluate female LS carriers' attitudes towards regular gynecological surveillance and factors influencing their decision-making on prophylactic surgery that have not been well documented. Pain experienced during endometrial biopsies was also evaluated. Postal questionnaires were sent to LS carriers undergoing regular gynecological surveillance. Questionnaires were sent to 112 women with LS, of whom 76 responded (68%). Forty-two (55%) had undergone prophylactic hysterectomy by the time of the study. The majority of responders (64/76; 84.2%) considered surveillance appointments beneficial. Pain level during endometrial biopsy was not associated with the decision to undergo prophylactic surgery. The level of satisfaction the women had with the information and advice provided during surveillance was significantly associated with the history of prophylactic hysterectomy (satisfaction rate of 73.2% versus 31.8% of nonoperated women, p = 0.003). The women who had undergone prophylactic surgery were older than the nonoperated women both at mutation testing (median of 42.3 years versus 31.6 years, p <0.001) and at the time of the study (median of 56.9 years versus 46.0 years, respectively, p <0.001). Women with LS pathogenic variants have positive experiences with gynecological surveillance visits, and their perception of the quality of the information and advice obtained plays an important role in their decision-making concerning prophylactic surgery.Peer reviewe

Lynch Syndrome in Finnish Women : Endometrial cancer risk factors, surveillance, prophylactic surgery and family planning

Tämän väitöskirjatyön tutkimukset suunniteltiin tiedon lisäämiseksi Lynchin syndrooman (LS) kantajien gynekologisesta terveydestä, riskitekijöistä ja psykososiaalisista näkökulmista. LS on yleisin tunnettu syöpäriskiä lisäävä perinnöllinen häiriö ja se lisää merkittävästi riskiä ruoansulatauskanavan, virtsateiden sekä kohdun runko-osan ja munasarjojen syöpiin. Lynchin syndrooman kantajilla on jonkin DNA:n perimän vaurioita korjaavan mismatch repair (MMR) -geenin patogeeninen variantti. Kohtu- ja munasarjasyövän riskin poistamiseksi LS-kantajille suositellaan kohdun ja munasarjojen poistoa, kun lapsiluku on täynnä. Heille on tarjottu myös gynekologista seurantaa. Väitöskirjan tavoitteena oli karakterisoida Lynchin syndroomaan (LS) liittyvän patogeenisen geenivariantin kantajien kohtusyövän riskiin vaikuttavia tekijöitä. Lisäksi haluttiin tutkia suhtautumista ennaltaehkäiseviin leikkauksiin sekä LS- diagnoosin vaikutuksia lisääntymisterveyteen ja psykososiaaliseen hyvinvointiin. Tutkimusväestö koostui 223 geenitestauksella varmistetusta Finnish Lynch syndrome research registry (LSRFi) -rekisteriin kirjatusta naispuolisesta kantajasta sekä 290 Tampereen ylipistollisen sairaalan (TAUH) potilastietokannasta kerätystä kohtusyöpään sairastuneesta potilaasta ilman perinnöllistä syöpäalttiutta. Tiedot kerättiin postitse kyselylomakkeilla, joissa oli kysymyksiä kohtusyövän riskitekijöistä sekä kantajien kokemuksista liittyen seurantaan, ennaltaehkäiseviin leikkauksiin, perhesuunnitteluun ja psykososiaaliseen hyvinvointiin. Ensimmäisessä osatyössä verrattiin 50 kohtusyöpään sairastuneen LS-kantajan ja 110 verrokki-kohtusyöpäpotilaan riskitekijöitä. Nämä tekijät eivät eronneet merkitsevästi ryhmien välillä, mutta endometrioosia vaikutti esiintyvän enemmän LS-kantajilla. Kohtusyövän riskitekijöitä kartoitettiin lisää 136 LS-kantajan retrospektiivisellä kohorttitutkimuksella. Merkittävä yhteys kohonneeseen kohtusyövän riskiin todettiin muuttuja-analyyseissa tyypin II diabeteksella, hyperkolesterolemialla ja hormonikorvaushoidon pitkäaikaisella käytöllä. Kolmas osatyö oli kuvaileva tutkimus, jossa selvitettiin 76 LS-kantajan osalta ennaltaehkäisevän leikkaushoidon päätöksentekoon vaikuttavia tekijöitä. Heistä 55% oli jo leikattu. Merkitsevästi päätökseen vaikuttavia tekijöitä ei havaittu. Suurin osa piti tarjottua seurantaa hyödyllisenä. Leikkaukseen jo päätyneiden joukossa tyytyväisyys terveydenhuollon ammattilaisten antamaan tietoon ja neuvontaan oli merkittävästi yleisempää. Kohdun limakalvonäytteiden aiheuttama kipu arvioitiin pääosin lieväksi tai kohtalaiseksi. Neljännessä osatyössä kerättiin kuvailevaa tutkimusta varten LS -kantajien kokemuksia LS -diagnoosista ja sen vaikutuksista eri elämänalueisiin. Vastaajia oli 35. Heistä suurin osa ilmoitti, ettei LS ole vaikuttanut parisuhteeseen tai perhesuunnitteluun. Suurin osa oli tyytyväisiä seurantaan ja kiitollisia siitä. Väitöskirjatutkimus tarjoaa tietoa, jota voidaan hyödyntää, kun neuvotaan naispuolisia LS -kantajia. Tulokset rohkaisevat ohjaamaan kantajia noudattamaan terveellisiä elintapoja ja välttämään pitkäaikaista hormonikorvaushoitoa. Endometrioosin mahdollinen yhteys Lynchin syndroomaan on kiinnostava löydös tulevia tutkimuksia ajatellen. Seurannalla vaikuttaa olevan positiivisia psykososiaalisia vaikutuksia. Tuloksemme korostavat asiantuntijoiden antaman riittävän tiedon ja neuvonnan sekä empaattisen asenteen tärkeyttä. Geenitestauksen tuloksella ei vaikuta olevan negatiivista vaikutusta LS-kantajien minäkuvaan tai merkittävää roolia heidän perhesuunnittelussaan.The studies of this thesis were designed to gather further information on the gynecological health, risk factors and psychosocial aspects among carriers of Lynch Syndrome (LS). LS is the most common hereditary cancer-predisposing genetic disorder in the world and it significantly increases the cancer risk in the gastrointestinal tract, urinary tract, endometrium and ovaries. LS carriers have pathogenic variants of mismatch- repairing (MMR) genes repairing oncogenic damages of DNA. For the prevention of endometrial cancer (EC) and ovarian cancer (OC), risk- reducing hysterectomy and salpingo-oophorectomy are recommended for LS carriers after childbearing is complete. Gynecological surveillance has also been offered. This thesis aimed to characterize the factors modifying the risk of endometrial cancer among LS carriers. Moreover, female LS carriers’ reproductive health issues, attitudes towards risk-reducing surgery and psychological reactions associated with germline testing were assessed. The study population consisted of 223 female verified LS pathogenic variant carriers identified from the Finnish Lynch syndrome research registry (LSRFi) and 290 non- carrier control EC patients from the Tampere University Hospital (TAUH) patient records. Data were collected by postal questionnaires which contained questions regarding EC risk factors and experiences on gynecological surveillance, risk- reducing surgery, reproductive health and psychosocial wellbeing. Patient record information was partially available for confirming the data. In the first study we compared the lifestyle-related EC risk factors between 50 LS carriers and 110 non-carriers diagnosed with EC. The risk factors did not differ significantly between these groups, but the results showed a tendency for higher prevalence of endometriosis among the LS carriers. The EC risk-modifying factors were further evaluated in a retrospective cohort study of 136 LS carriers. Type II diabetes, hypercholesterolemia and long-term use of HRT had significant associations with an elevated risk of EC among LS carriers in univariable and multivariable Cox regression analyses. The aim of the third, descriptive study was to investigate the factors associated with the decision regarding the uptake of risk-reducing surgery. Seventy-six responders implicated no external factors affecting their decisions concerning the surgery. A majority of them considered the gynecological surveillance beneficial. Fifty-five percent had the prophylactic surgery performed at survey. The percentage of the responders who were satisfied with the counselling and information provided by medical experts was significantly higher among the prophylactically operated LS carriers. Pain experienced during endometrial sampling was mainly low or moderate. In the fourth study we gathered information on the subjective experiences of genetic testing, and its’ impacts among LS carriers. In this descriptive study, the majority of the 35 responders did not report LS as having any influence on their intimate relationships and only 20% reported an effect on their reproductive decisions. Most of the carriers implicated thankfulness and satisfaction with the gynecological surveillance provided. In conclusion, the studies of this thesis provided data that could be applied to clinical counselling with female LS carriers. The results encourage the carriers to be recommended to maintain a healthy lifestyle and to avoid long-term HRT. The possible association of endometriosis with LS is an interesting target for future research. Surveillance seems to have positive psychosocial effects on the LS carriers. Our results emphasize the importance of adequate information and counselling with an emphatic attitude, provided by medical experts. The germline testing as such seems not to have a negative impact on the female LS carriers’ self-image or to play a major role in their reproductive health decisions