Congenital Uterine Anomalies: Identifying Cancer Associations and Genetic and Environmental Factors to Improve Clinical Care

Study Overview
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Brief Summary
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The purpose of this research study is to learn more about the health outcomes associated with congenital uterine anomalies (CUAs), and the possible environmental and genetic causes of the condition. The researchers plan to investigate whether any cancer associations (with breast, renal, ovarian, vaginal and uterine cancers) exist in females with CUAs. The investigator will also investigate any environmental and genetic factors that may be responsible for causing CUAs.

Detailed Description
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Aim 1: To identify female subjects diagnosed with a Congenital Uterine Anomaly (CUA) receiving care at Yale New Haven Health. Aim 2: Identify (i) the prevalence of renal, breast, ovarian, uterine and vaginal cancers associated with CUAs, and (ii) the association of environmental factors, via a survey obtained by phone, email or interview. Aim 3: Conduct genetic evaluation of the index subjects, parents, sister(s) (as feasible), and female offspring to identify potential causes and patterns of inheritance using whole exome sequencing (WES) and microarray. Following informed consent, blood will be collected for genetic evaluation. DNA will be extracted from EDTA-blood and analyzed using an integrated approach of microarray for copy number variations (CNV), and Whole Exome Sequencing (WES) for Single Nucleotide Variation (SNV). Undertaking review of the medical records will identify the cohort of patients we wish to survey to then ascertain further information regarding their CUA diagnosis and other related details. The information to be elicited from the survey are outlined in the attached survey questions. Key associations we seek to investigate include (1) the type and prevalence of renal, breast, ovarian, uterine and vaginal cancers among patients with Mullerian Anomaly, and (2) identifying potential in-utero exposure to particular environmental agents in patients with CUAs. Review of the medical records will enable us to undertake this first key step of establishing a cohort of subjects with MA and an initial data set related to their specific health information. We anticipate further investigations may build upon this initial data set, both with the cohort established, and more broadly with collaborators and additional national and international cohorts of patients with MA.

Official Title
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Congenital Uterine Anomalies: Identifying Cancer Associations and Genetic and Environmental Factors to Improve Clinical Care

Conditions
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Congenital Uterine Anomaly

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: females age: 13 or older encounters limited to: Yale New Haven Hospital, Bridgeport Hospital, Greenwich Hospital and Lawrence+ Memorial Hospital. diagnosis of any variation of CUA Exclusion Criteria: who will decline to participate in a study upon contact non-English speaking except Spanish speaking unable to participate in consent or assent process due to mental disability

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with Congenital Uterine Anomalies (CUA)<br>The rates of renal, breast, uterine, ovarian and vaginal cancers in women who have been diagnosed with a CUA will be studies | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of breast cancer in women with CUA's compared to women without CUA's | Prevalence of breast cancer in women with CUA's compared to women without CUA's will be measured | 6-months | 
| Prevalence of ovarian cancer in women with CUA's compared to women without CUA's | Prevalence of ovarian cancer in women with CUA's compared to women without CUA's will be measured | 6-months | 
| Prevalence of uterine cancer in women with CUA's compared to women without CUA's | Prevalence of uterine cancer in women with CUA's compared to women without CUA's will be measured | 6-months | 
| Prevalence of cervical cancer in women with CUA's compared to women without CUA's | Prevalence of cervical cancer in women with CUA's compared to women without CUA's will be measured | 6 month | 
| Prevalence of vaginal cancer in women with CUA's compared to women without CUA's | Prevalence of vaginal cancer in women with CUA's compared to women without CUA's will be measured | 6 month | 
| Prevalence of renal cancer in women with CUA's compared to women without CUA's | Prevalence of renal cancer in women with CUA's compared to women without CUA's will be measured | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole exome sequencing (WES) and microarray | WES and microarray will be conducted in subjects with CUAs. The discovery of possible causative genes would be measured using yes/no outcome variable. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer associations, Environmental factors