Gene-specific risk of syndrome-associated cancers in first-degree relatives of pancreatic cancer patients with pathogenic/likely pathogenic variants

Sep 28, 2026

Uploaded by Noah

Gene-specific cancer risk estimates are developed to improve genetic counseling for first-degree relatives (FDRs) in families of pancreatic cancer patients carrying germline pathogenic/likely pathogenic variants. Using the prospective Mayo Clinic Biospecimen Resource for Pancreas Research registry, 4,562 pancreatic cancer patients previously underwent germline testing, and 234 probands with pathogenic/likely pathogenic variants across nine genes contributed questionnaire-based FDR data. Six cancer types were analyzed via standardized incidence ratios, revealing elevated ovarian, breast, uterine, pancreatic, colon, and melanoma risks depending on the gene involved.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages1

Reading Time3 min

AccessFree to download

Abstract Supplement

Gene-specific cancer risks in FDRs of pancreatic cancer probands

18 JCTS 2023 Abstract Supplement 65 Gene-specific risk of syndrome-associated cancers in first-degree relatives of pancreatic cancer patients with pathogenic/likely pathogenic variants Xuan Chen1, Kari G. Rabe2, Margaret A. Meyer3, Jennifer L. Kemppainen4, Masayasu Horibe5, Shruti Chandra6, Shounak Majumder7, Gloria M. Petersen6 1Center for Clinical and Translational Science, Mayo Clinic 2 Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic 3 Department of Medical and Molecular Genetics, Indiana University School of Medicine 4Center for Individualized Medicine, Mayo Clinic 5 Division of Gastroenterology and Hepatology Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan 6 Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic 7 Division of Gastroenterology and Hepatology, Mayo Clinic This abstract is based on unpublished data. OBJECTIVES/GOALS: The estimates of unbiased first-degree relatives (FDRs) risk of cancers would enhance genetic counseling of at-risk FDRs in families where the pancreatic cancer (PC) proband carrying a germline variant. This study aims at quantifying gene-specific risks of six cancers among FDRs of PC patients with germline variants in cancer-associated genes. METHODS/STUDY POPULATION: In the prospective, clinic-based Mayo Clinic Biospecimen Resource for Pancreas Research registry, 4,562 PC patients had previously undergone germline genetic testing for pancreatic cancer-associated genes through either research studies or clinical testing. Of these, 234 PC probands were found to carry germline pathogenic/likely pathogenic variants (PLPV) among 9 genes of interest and had provided detailed demographic and cancer data on their FDRs by questionnaire. We focused on six cancer types (ovary, breast, uterus, pancreas, colon, and malignant melanoma) in FDRs as reported by the probands. Standardized incidence ratios were calculated to estimate risk of six cancers among FDRs of PC patients carrying PLPV by gene. RESULTS/ANTICIPATED RESULTS: 1,670 FDRs (mean age 58.1+17.8SD; 48.9% female) were included in the study. We found significantly increased risk of ovarian cancer in female FDRs of PC probands who carry PLPV in BRCA1 (SIR 9.49, 95% CI:3.06-22.14) or BRCA2 (3.72, 95%CI:1.36-8.11), and breast cancer risks were higher with BRCA2 (2.62, 95%CI:1.89-3.54) . Uterine cancer risk was increased in FDRs of PC probands who carry PLPV for Lynch Syndrome mismatch repair (MMR) (6.53, 95% CI:2 .81-12.86) . PC risk was also increased (ATM 4 .53, 95% CI:2.69-7.16; BRCA2 3.45, 95%CI:1.72-6.17; CDKN2A 7.38, 95% CI:3 .18-14. 54; PALB2 5 .39, 95%CI:1 .45-13.79) . Increased colon cancer risk was observed in FDRs of probands who carried MMR PLPV (5.83, 95%CI:3.70-8.75), while melanoma risk was elevated for FDRs of probands with CDKN2A PLPV (7.47, 95%CI:3.97- 12.77) . DISCUSSION/SIGNIFICANCE: PLPV in nine syndromeassociated genes in PC probands are associated with increased risk of six cancers in FDRs. The findings underscore the importance of risk estimation of various other cancers in PC families for screening, early detection, intervention, and cascade genetic testing. 67 Lipid metabolism and synthesis pathway analysis of Sigma-2 Receptor/TMEM97 in breast cancer cells Aladdin Riad, David Mankof, Robert H. Mach University of Pennsylvania OBJECTIVES/GOALS: Breast cancer has an increased requirement for lipids. The sigma-2 receptor plays a critical role in the effective uptake of lipoproteins by forming a complex with the LDL Receptor. We investigate the role of the sigma02 receptor in modulating lipid uptake pathways in breast cancers, and how this can be leveraged as a viable therapeutic strategy. METHODS/STUDY POPULATION: CRISPR/Cas9 will be used to ablate TMEM97 in the MDAMB231 and MCF7 cell lines. This study seeks to identify pathways that are dysregulated upon TMEM97 knockout (KO) by characterizing RNASe

FAQs

What is the main purpose of this study?

To quantify gene-specific cancer risks among first-degree relatives (FDRs) of pancreatic cancer patients who carry germline pathogenic/likely pathogenic variants.

How were participants identified and data collected?

Pancreatic cancer probands from the Mayo Clinic registry who had germline testing were selected, and detailed demographic and cancer data on their FDRs were collected by questionnaire.

Which cancer types were assessed for FDR risk?

Six cancers were evaluated: ovary, breast, uterus, pancreas, colon, and malignant melanoma, with risk estimated by standardized incidence ratios by gene.

Sep 28, 2026

Uploaded by Noah