Universal Screening for Lynch Syndrome in Women With Endometrial and Non-Serous Ovarian Cancer

Universal Screening for Lynch Syndrome in Women With Endometrial and Non-Serous Ovarian Cancer

This study will maximize identification of women with Lynch Syndrome using an enhanced screening strategy to identify those at risk. These women will be referred to genetic counselling for testing and those found to have Lynch Syndrome will be asked to invite first degree relatives to participate and undergo genetic testing for Lynch Syndrome. Screening guidelines and risk reducing surgery options for participants found to have Lynch Syndrome will be reinforced by the study and adherence to these guidelines will be assessed annually for ten years following Lynch Syndrome diagnosis to assess the impact and cost-effectiveness of this enhanced screening approach.

Lynch Syndrome increases an individual's risk for several cancers, such as colorectal, endometrial (EC) and certain types of ovarian cancer (OC). Lynch Syndrome is caused by inherited changes in mismatch repair (MMR) genes. In this study we will establish the proportion of EC and OC patients with Lynch Syndrome. We will screen all EC and OC patients by performing MMR immunohistochemistry (IHC) on their surgical specimen. These data will then be used along with family history data to determine which women are at high risk of Lynch Syndrome. We will facilitate the referral of all women at risk for Lynch Syndrome to genetic counselling on behalf of their treating physician. First degree relatives of those patients found to have Lynch Syndrome who consent to participate in the study will also be referred to genetics by the study PI. We will encourage all participants found to have Lynch Syndrome to attend regular colonoscopy screening to prevent colorectal cancer, and (for females with Lynch Syndrome) consideration of gynecologic risk reducing surgery to prevent endometrial and ovarian cancers. We will assess adherence to Lynch Syndrome screening guidelines in this population and will determine if our universal screening strategy is feasible and cost-effective for widespread implementation across Canada in an effort to prevent Lynch Syndrome associated cancers in women and their families. In addition to this, consenting patients may provide blood and tumour tissue samples for sequencing studies which will investigate the genetic basis for Lynch Syndrome and shed light on cases of MMR loss in the absence of germline mutation.

Inclusion Criteria (Patients):

• 18-70 years old
• endometrial cancer (all grades, stages and histologic subtypes except stromal sarcoma, carcinosarcoma)
• cancer diagnosed within 6 months of consent
• tumour tissue available for MMR IHC
• willing and able to give informed consent for participation in study

Exclusion Criteria (Patients):

• patients under 18 years old or over 70 years old
• patients with uterine adenosarcoma, leiomyosarcoma or endometrial stromal sarcoma
• patients with pure serous or pure mucinous ovarian carcinoma
• patients unwilling or unable to participate in the informed consent process

Inclusion Criteria (First-degree Relatives)

• minimum 18 years old
• reside in Canada
• willing and able to give informed consent for participation in study

Exclusion Criteria (First-degree Relatives):

• under 18 years old
• reside outside of Canada
• unwilling or unable to participate in the informed consent process