Germline Mutations Associated With Hereditary Pancreatic Cancer in Unselected Patients With Pancreatic Cancer in Mexico

Completed

• Conditions: Pancreatic Cancer; Pancreatic Adenocarcinoma

• Registration Number: NCT05305001
• Lead Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Brief Summary

Pancreatic cancer is a highly lethal disease. The cause of pancreatic cancer is multifactorial. However, around 10% of cases are associated with hereditary predisposition. Germline mutations in BRCA1 and BRCA2, CDKN2A, STK11, DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2), PALB2, FANCC, FANCG, and ATM have been associated with an increased risk for pancreatic cancer. The prevalence of these germline mutations varies across populations. For instance, the prevalence of BRCA1/2 germline mutations in high-risk populations can be up to 20%. On the other hand, in unselected patient population, the prevalence of BRCA1/2 germline mutations is 5-7%. In Mexican population, data on the prevalence of BRCA1/2 germline mutations in patients with pancreatic cancer are lacking. Identification of BRCA germline mutations in patients with pancreatic cancer has implications for treatment. Also, it allows genetic testing and counselling for family members. This study will determine the prevalence of germline mutations associated with hereditary pancreatic cancer using a comprehensive gene panel in an unselected cohort of patients with pancreatic adenocarcinoma in Mexico.

Detailed Description

This is an observational study to estimate the prevalence of germline mutations in patients with pancreatic cancer. Eighty four genes will be analyzed, all of which have been associated with hereditary cancer. The genes are included on Invitae Multi-Cancer Panel ®, performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology. The 84 genes include: AIP, ALK, APC, ATM, AXIN2, BAP1, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, CASR, CDC73, CDH1, CDK4, CDKN1B, CDKN1C, CDKN2A, CEBPA, CHEK2, CTNNA1, DICER1, DIS3L2, EGFR, EPCAM, FH, FLCN, GATA2, GPC3, GREM1, HOXB13, HRAS, KIT, MAX, MEN1, MET, MITF, MLH1, MSH2, MSH3, MSH6, MUTYH, NBN, NF1, NF2, NTHL1, PALB2, PDGFRA, PHOX2B, PMS2, POLD1, POLE, POT1, PRKAR1A, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RB1, RECQL4, RET, RUNX1, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, SMARCA4, SMARCB1, SMARCE1, STK11, SUFU, TERC, TERT, TMEM127, TP53, TSC1, TSC2, VHL, WRN, WT1.

Study Timeline

• Study Start: 2020-09-09
• Study First Submitted: 2021-06-02
• Study First Submitted QC: 2022-03-22
• Study First Posted: 2022-03-31
• Primary Completion: 2022-06-30
• Study Completion: 2022-06-30
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-17
• Last Update Posted: 2022-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 107

Inclusion Criteria

• Female and male participants ≥ 18 years of age.
• Diagnosed within the previous 6 months with histologically confirmed pancreatic adenocarcinoma stage I to IV.
• Participant provides written informed consent for the study.
• Participant must agree to sample collection and genetic testing using the Invitae Multi-Cancer Panel ®.

Exclusion Criteria

• Diagnosed with pancreatic adenocarcinoma more than 6 months before presenting to the clinical site.
• Diagnosed with intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, pancreatic neuroendocrine tumors.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
BRCA 1/2 germline mutation prevalence	15 months	To estimate the prevalence of BRCA1 and BRCA2 germline mutations in patients who present to the clinical site within 6 months of a histologically confirmed diagnosis of pancreatic adenocarcinoma.

Secondary Outcome Measures

Name	Time	Method
Clinical and pathological characteristics	15 months	To describe the clinical and pathological characteristics of patients with pancreatic adenocarcinoma and BRCA1, BRCA2 and other germline mutations.
Other germline mutation prevalence	15 months	To estimate the prevalence of other germline mutations associated with hereditary pancreatic cancer in patients who present to the clinical site within 6 months of a histologically confirmed diagnosis of pancreatic adenocarcinoma.

Trial Locations

Locations (1)

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; 🇲🇽 Mexico City, Mexico