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

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.

Study Overview

• Status: Recruiting
• Conditions: Congenital Uterine Anomaly

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Alla Vash-Margita, MD; Phone Number: 203-785-4010; Email: alla.vash-margita@yale.edu
• Study Contact Backup: Name: Miranda Margetts, PhD; Email: miranda.margetts@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Yale University
      • Contact: Monica G Konstantino, RN; Phone Number: 203-785-5816; Email: monica.konstantino@yale.edu
      • Principal Investigator: Alla Vash-Margita, MD, FACOG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women and girls who have received care within the Yale New Haven Health system and have a CUA diagnosis Anticipated number - approximately 300 subjects Age range - from 13 years old and older Health status - able to participate in consent and assent (based on age) process

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with Congenital Uterine Anomalies (CUA); 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?

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

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Alla Vash-Margita, MD, Yale University; Principal Investigator: Emanuele Pelosi, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2021
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Environmental factors; Cancer associations
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Urogenital Abnormalities
• Other Study ID Numbers: 2000028592; 1R03HD109641-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No