CTNNA1 Familial Expansion Study

Recruiting

• Conditions: Cancer Gene Mutation; Breast Cancer; Gastric Cancer

• Registration Number: NCT05126290
• Lead Sponsor: Abramson Cancer Center at Penn Medicine

Brief Summary

The goal of the CAFÉ Study is to determine the cancer risks associated with germline CTNNA1 loss-of-function variants.

Detailed Description

The CAFÉ Study aims to determine the degree to which loss-of-function variants in the CTNNA1 gene are associated with hereditary cancers, including gastric cancer, breast cancer, as well as other cancers that may be associated with this gene. By obtaining personal and family history information from individuals who carry a CTNNA1 loss-of-function variant and their family members, this study will aim to better define CTNNA1 associated cancer risks and determine whether there is a genotype/phenotype correlation for CTNNA1 loss-of-function variants. This information will be important for the future cancer risk management of individuals who carry a CTNNA1 loss-of-function variant.

Study Timeline

• Study Start: 2021-03-16
• Study First Submitted: 2021-11-02
• Study First Submitted QC: 2021-11-10
• Study First Posted: 2021-11-19
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-06
• Primary Completion: 2026-01-01
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• 18 years of age and older
• Participants must be carrier, or a first degree relative of a carrier, of a CTNNA1 loss-of-function variant defined as: a variant predicted to lead to protein truncation (nonsense and frameshift variants), a large deletion of one or more exons, or a consensus splice site variant predicted to disrupt splicing in CTNNA1. CTNNA1 loss-of-function variants do not need to be classified as pathogenic or likely pathogenic to be included.
• Participants must be able to understand and read English
• Participants must be able to provide informed verbal or written consent

Exclusion Criteria

• Less than 18 years of age
• Individuals who do not carry a CTNNA1 loss-of-function variant and are not a first degree relative of a CTNNA1 loss-of-function variant carrier.
• Individuals who cannot speak and read English
• Major psychiatric illness or cognitive impairment that in the judgement of the study investigators or study staff would preclude study participation
• Unable to comply with the study procedures as determined by the study investigators or study staff

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of CTNNA1 genotypes associated with a cancer phenotype	Through study completion, which will average 1 year	Using collected family pedigrees from enrolled participants, we will correlate estimated cancer risk for CTNNA1 loss-of-function variant carriers with their CTNNA1 genotype, to determine if there is a significant genotype-phenotype correlation observed.
Rate of cancer amongst carriers of CTNNA1 loss-of-function variants	Through study completion, which will average 1 year	After collecting personal and family cancer history from enrolled participants, family pedigrees will be utilized to calculate cancer risk estimates for for CTNNA1 loss-of-function variant carriers including gastric cancer risk, breast cancer risk, as well as risk of other cancers currently not known to be associated with CTNNA1 variants gene.

Trial Locations

Locations (1)

Abramson Cancer Center of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States