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

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.