Germline Mutations Associated With Hereditary Pancreatic Cancer in Unselected Patients With Pancreatic Cancer in Mexico
Study Details
Study Description
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.
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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 Design
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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 Outcome Measures
- The proportion of blood relatives of germline mutation carriers who accept genetic counseling and genetic testing [15 months]
Number of first degree relatives with a positive genetic test result. Number of first degree relatives with genetic counseling and genetic testing.
- The proportion of germline mutation carriers who accept pancreatic cancer surveillance. [up to 15 months]
Number of germline mutation carriers included in a surveillance protocol assessed by abdominal imaging.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Female and male participants ≥ 18 years of age.
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Diagnosed within the previous 6 months with histologically confirmed pancreatic adenocarcinoma stage I to IV.
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Participant provides written informed consent for the study.
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Participant must agree to sample collection and genetic testing using the Invitae Multi-Cancer Panel ®.
Exclusion Criteria:
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Diagnosed with pancreatic adenocarcinoma more than 6 months before presenting to the clinical site.
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Diagnosed with intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, pancreatic neuroendocrine tumors.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán | Mexico City | Mexico | 14080 |
Sponsors and Collaborators
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Investigators
- Principal Investigator: Fidel D Huitzil Meléndez, MD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study Documents (Full-Text)
More Information
Additional Information:
Publications
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- HEM-3331-20-20-1