Is Pancreatic Cancer Hereditary From Grandparents

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Who Should Get Genetic Testing

Is Pancreatic Cancer Hereditary? – Mayo Clinic

People with a strong family history of pancreatic cancer, particularly if there is also a family history of breast/ovarian or colon cancer, are often advised to consider genetic testing to see if there is a specific gene that may have triggered the disease in their family.

But recently the National Comprehensive Cancer Network took its recommendation for genetic testing a step further: It now recommends that everyone who has pancreatic cancer be tested to see if they carry gene mutations that would put family members at risk.

Genetic testing is a nuanced process, however, and should start with a visit to a genetic counselor.

It gives you a better understanding of what kind of information youll get from the testing and the limitations of testing, Forman said.

For instance, testing may reveal that you dont carry any of the genes known to increase the risk of pancreatic cancer. However, having no genetic link doesnt necessarily mean you dont have a higher risk, Forman said.

Also, a higher risk doesnt necessarily mean a high risk, she said. Most of the time, youre looking at a 5 to 7 percent risk of pancreatic cancer, although that risk may be higher depending on family history. It is important to remember that even with a genetic risk, the majority of those people wont get pancreatic cancer.

Subjects And Ethics Statement

This study was approved by the Institutional Review Board of the University of Utah. All participants gave written consent, which included DNA sampling for molecular studies and access to medical records.

An initial set of pancreatic cancer cases were selected on the minimal requirements of personal history of cancer and having at least two grandparents in the genealogy data represented in the Utah Population Database . These patients were screened with a 34-gene custom research panel. Individual family members were then linked to statewide cancer, demographic, and medical information . Ages at diagnosis and family cancer history were obtained from the UPDB after sequencing and variant evaluation. Additional subjects were selected on the basis of being newly diagnosed pancreatic cancer cases ascertained at the HCH from July 2014 to April 2017 . The pancreatic cancer cases ascertained during the interval July 2014November 2015 were screened with a 59-gene custom research panel, and the cases ascertained during the interval December 2015April 2017 were screened with a 14-gene custom clinical panel.

Identification Of Pathogenic Variants And Hip

In an initial set of 66 pancreatic cancer cases unselected for family history of cancer, 4 pathogenic variants were identified in BRCA2, MSH6, PALB2, and STK11. After filtering VUS, 2 HiP-VUS in ATM remained . After weighting, 8.5% of these pancreatic cancer cases carried a variant with potential medical management impact for relatives.

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Hereditary Vs Familial Pancreatic Cancer: Associated Genetic Syndromes And Clinical Perspective

Luciano M. Vargas, MDOncology

Pancreatic ductal adenocarcinoma is a disease marked by high rates of mortality, with only about 7% of patients surviving 5 years after diagnosis. Here, the authors present a demonstrative case and review the available data on hereditary and familial PDAC.

Introduction

Pancreatic ductal adenocarcinoma has one of the worst prognoses among major cancers. In 2020 in the United States, it is expected to be the third-leading cause of cancer mortality, following lung and colorectal cancer, with 47,050 deaths in both genders combined .1

The average lifetime risk of pancreatic cancer is about 1 in 65 , with a 5-year survival rate of 7%.2 Although incidence is roughly equal in both genders, African Americans have a higher incidence than any other racial group.3 Older age is among the main risk factors for the development of PDAC median age at diagnosis is 71 years.4 Apart from family history, which can influence the likelihood of PDAC development, other risk factors include tobacco and alcohol abuse, chronic pancreatitis, dietary factors, obesity, and type 2 diabetes mellitus.5-8 The incidence of PDAC in the United States has increased in recent years, possibly due to the aging population and the increasing prevalence of obesity.

Case

Discussion

Outcome of the Case

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

How Can I Reduce My Risk Of Pancreatic Cancer

Roger L. Kerns Benefit

If there is pancreas cancer in your family, there are things that you should consider doing to reduce your risk: quit smoking, lose weight , consider genetic testing and/or participate in screening trials for early cancer detection.

Third Degree Relatives – First cousins, great-aunts and uncles

An inherited genetic variation in DNA that you are born with

Second Degree Relatives – Aunts, uncles, grandparents, nieces and nephews

First Degree relatives – Blood relatives in your immediate family: parents, children, and siblings

This is an experimental type of treatment. It is a medication made of killed or weakened cells, organisms or manufactured materials, which is used to boost the body’s immune system. Ideally, this will allow the body to fight and kill the cancer cells more effectively. Vaccines include whole killed cancer cells or specific proteins from the cancer.

Also known as a pancreatoduodenectomy, the Whipple procedure is the surgery typically performed to remove cancers of the head of the pancreas . It typically involves the surgical removal of the head of the pancreas, a portion of the duodenum and a portion of the bile ducts.

The part of the pancreas that bends backwards, hooking around two very important blood vessels, the superior mesenteric artery and vein. The word “uncinate” comes from the word uncus which means “hook.”

Unable to be surgically removed. This usually means that the cancer has spread beyond the areas that can be removed surgically.

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Identification And Screening Of Individuals At Increased Risk For Pancreatic Cancer With Emphasis On Known Environmental And Genetic Factors And Hereditary Syndromes

David Chu1, Wendy Kohlmann2, Douglas G Adler3

1Department of Internal Medicine, 2High Risk Cancer Clinics, and 3Division of Gastroenterology and Hepatology Huntsman Cancer Center, University of Utah School of Medicine. Salt Lake City, UT, USA

*Corresponding Author:
Gastroenterology and Hepatology, Huntsman Cancer Center,University of Utah, Salt Lake City, UT, USAPhone: +1-801.581.5036

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Abstract

Despite recent diagnostic and therapeutic advances, pancreatic cancer still carries a poor prognosis. Screening high-risk individuals is a relatively new concept with regards to pancreatic cancer but is an area of intense study. Significant effort has been invested in identifying risk factors for pancreatic cancer. Risk factors for pancreatic cancer can be classified into three broad categories: demographic, environmental , and hereditary predisposition. This manuscript will review the risk factors and genetic syndromes associated with increased risk of developing pancreatic cancer, the role of genetic testing in the evaluation of high-risk patients, the available serologic and imaging tests that can be used to screen these individuals, and will summarize the available literature on attempts at pancreatic cancer screening to date.

Introduction and Epidemiology

Pathophysiology of Pancreatic Cancer

Risk Factors

Challenges in Screening and Treating Pancreatic Cancer

Familial Pancreatic Cancer

Hereditary Pancreatitis

References

How Can Knowing About An Inherited Genetic Mutation Help Patients

Besides increasing risk for pancreatic cancer, some germline mutations affect treatment options for those who get the disease. Using the patients biology to figure out the best treatment options for a person is called precision medicine. Patients who receive treatment based on their biology can live longer.

As soon as possible after diagnosis, the Pancreatic Cancer Action Network strongly recommends all pancreatic cancer patients get genetic testing for inherited mutations and biomarker testing of their tumor tissue. These tests will help the healthcare team figure out the best treatment options for the patient and inform family members of risk.

Patients should discuss both tests with their care team. The tests can be available through their treating institution or PanCANs Know Your Tumor® precision medicine service.

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Types Of Family Cancer

A small number of families have an increased risk of certain cancers due to a change in their genes or inherited disorders. There are several types of family cancer outlined in the information below.

Familial adenomatous polyposis

Familial adenomatous polyposis is a rare inherited condition. Less than 1% of all bowel cancers in the general population are due to FAP.

People with FAP usually develop multiple small growths, called polyps, in the colon. The polyps are adenomatous, which means they are immediate precursors to colon cancer. These generally appear in the teenage years and, if left untreated, inevitably progress to bowel cancer.

For those who have inherited the gene change, regular bowel surveillance is extremely important. Screening, generally by colonoscopy, should start between the age of 10 to 15 years.

Hereditary non-polyposis colorectal cancer

Hereditary non-polyposis colorectal cancer is a rare inherited bowel cancer syndrome. Less than 5% of all bowel cancer cases are HNPCC.

People with HNPCC often develop large bowel cancer before the age of 50. They commonly have one or more adenomas in the bowel.

People not only have an increased chance of developing bowel cancer, but also cancer of the uterus and other types of cancer including ovary, kidney, ureter small bowel, stomach and pancreas.

Hereditary breast and ovarian cancer

Their names come from the abbreviation of the genes ‘Breast Cancer One’ and ‘Breast Cancer Two’.

Neurofibromatosis 2

Retinoblastoma

What Are The Estimated Cancer Risks Associated With Fpc

Hereditary Pancreatic Cancer

The lifetime risk of pancreatic cancer for the average individual without a family history of pancreatic cancer is approximately 1%. Individuals with a family history of pancreatic cancer are at an increased lifetime risk for developing pancreatic cancer. This risk is likely higher for individuals from a family with FPC. The following cancer risk estimates are generalized and should be interpreted with caution since the actual risk for each individual may be different:

  • Individuals from FPC families who have 1 first-degree relative, meaning a parent, sibling, or child, with pancreatic cancer are estimated to have an increased lifetime risk of pancreatic cancer that is 3 to 5 times higher than the general population.
  • Individuals from FPC families who have 2 first-degree relatives with pancreatic cancer are estimated to have an increased lifetime risk of pancreatic cancer that is 5 to 7 times higher than the general population.
  • Individuals from FPC families who have 3 or more first-degree relatives with pancreatic cancer are estimated to have an increased lifetime risk of pancreatic cancer that may be up to 30 times higher than the general population.

Tobacco use increases an individuals lifetime risk of pancreatic cancer, regardless of their family history. Tobacco use may significantly increase the risk of pancreatic cancer for individuals from FPC families.

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What Is A Surveillance Program

In a surveillance, early detection or screening program, doctors actively check people who are at risk of getting pancreatic cancer.

The goal is to find early pancreatic cancer and pre-cancerous lesions. Patients whose disease is found in its earlier stages have better outcomes. This is because they are more likely to be able to have surgery.

Surveillance programs usually use imaging tests to watch patients. They may also collect blood or pancreatic fluids to test.

Benefits of taking part in a surveillance program include:

  • Knowledgeable doctors monitoring you
  • Possible help from new diagnostic tests
  • Helping advance early detection efforts

Before enrolling in a surveillance program, you should understand the risks and benefits of screening. The healthcare professionals running the program can help you with this.

Dna Repair Defects And Increased Cancer Risk

Many cancer syndromes are due to an inherited impairment in DNA repair capability. When an inherited mutation is present in a DNA repair gene, the repair gene will either not be expressed or expressed in an altered form. Then the repair function will likely be deficient, and, as a consequence, DNA damages will tend to accumulate. Such DNA damages can cause errors during DNA synthesis leading to mutations, some of which may give rise to cancer. Germ-line DNA repair mutations that increase the risk of cancer are listed in the Table.

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Pancreatic Cancer Can Be Hereditary

Cancer of the pancreas is a genetic disease which means that it is caused by changes in DNA. These changes can be inherited or they can be acquired . The inherited changes explain why cancer of the pancreas runs in some families, and the acquired changes can be the result of either bad luck during cell replication or by exposure to carcinogens such as those found in cigarette smoke. Learn more about non-familial causes of pancreatic cancer.

About 5-10% of pancreatic cancer patients have another close relative who has also developed pancreatic cancer. Individuals with a family history of pancreatic cancer are more likely to have an inherited mutation in a gene that increases their risk of developing pancreatic cancer.

Pancreatic cancer is more common in some groups of people, including Ashkenazi Jews and African Americans.

Which Hereditary Conditions Raise My Chances Of Getting Cancer

Pancreatic Cancer Action Network (PanCAN)

Several hereditary conditions can raise your chances of getting cancer. Two of the most common are hereditary breast and ovarian cancer syndrome and Lynch syndrome.

  • People with HBOC syndrome have a higher risk for breast, ovarian, high-grade prostate, and pancreatic cancers.
  • People with Lynch syndrome have a higher risk for colorectal, uterine, and ovarian cancers.

Learn about medical options for people with HBOC syndrome or Lynch syndrome.

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If You Have Pancreatic Cancer In Your Family We Need Your Help

Third Degree Relatives – First cousins, great-aunts and uncles

An inherited genetic variation in DNA that you are born with

Second Degree Relatives – Aunts, uncles, grandparents, nieces and nephews

First Degree relatives – Blood relatives in your immediate family: parents, children, and siblings

This is an experimental type of treatment. It is a medication made of killed or weakened cells, organisms or manufactured materials, which is used to boost the body’s immune system. Ideally, this will allow the body to fight and kill the cancer cells more effectively. Vaccines include whole killed cancer cells or specific proteins from the cancer.

Also known as a pancreatoduodenectomy, the Whipple procedure is the surgery typically performed to remove cancers of the head of the pancreas . It typically involves the surgical removal of the head of the pancreas, a portion of the duodenum and a portion of the bile ducts.

The part of the pancreas that bends backwards, hooking around two very important blood vessels, the superior mesenteric artery and vein. The word “uncinate” comes from the word uncus which means “hook.”

Unable to be surgically removed. This usually means that the cancer has spread beyond the areas that can be removed surgically.

This term simply refers to a “mass” or neoplasm. For example, a collection of pus is a tumor. This is a general term that can refer to either benign or malignant growths.

The long thin part of gland in the left part of abdomen, near the spleen.

Some Pancreatic Cancers Are Hereditary

A trio of recent studies indicates that pancreatic cancer is, in some cases, linked to mutations passed down from generation to generation.

by Cheryl Platzman Weinstock

IN JANUARY 2010, Karen Huffmans mother died from pancreatic cancer. Huffman also knew that a great uncle of hers had died from the disease years earlier.

At first, she thought it was a fluky thing. But 18 months later, in May 2012, her father also died from pancreatic cancer.

Fifty-nine-year-old Huffman, who lives in Liberty, Pennsylvania, started talking about this strange coincidence with almost everyone, including her three siblings and her physicians. They all said it was nothing to worry about, she recalls. But she was still concerned about her and her familys risk.

In 2013, Huffman contacted the oncologist who took care of her mother. He referred Huffman to researchers studying pancreatic cancer risk at Johns Hopkins University in Baltimore, where she enrolled in the National Familial Pancreas Tumor Registry . The registry is open to pancreatic cancer patients and their families across the U.S. The researchers compile and analyze data from participants based on annual questionnaires and optional blood, saliva and/or tissue samples to learn more about pancreatic cancer risk and treatment.

In July 2017, one of Huffmans uncles was diagnosed with pancreatic cancer and died 10 months later. In December 2017, Huffmans younger sister Ellen, who was 56, was also diagnosed with pancreatic cancer.

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When The Gene Isn’t Known

While the above genetic syndromes account for ~20% of familial pancreatic cancer, it is clear that there are other, yet undiscovered familial pancreatic cancer genes. Scientists at Johns Hopkins are working diligently to discover the reasons why pancreas cancer runs in families without a known gene. The foundation for much of this research is the National Familial Pancreas Cancer Registry.

What Are The Screening Options For Fpc

Hereditary Pancreatic Cancer | Q& A

It is unknown if screening for pancreatic cancer is effective, and there is no routine screening for pancreatic cancer that is currently recommended for the general population. The medical community continues to research who to screen, which tests to use, and how often to use them.

Given that individuals from FPC families, or individuals with germline genetic mutations in BRCA1, BRCA2, PALB2, CDKN2A, ATM, MLH1, MSH2, MSH6, PMS2, STK11, and EPCAM, are at increased risk for pancreatic cancer, there is much interest in researching pancreatic cancer screening for these high-risk individuals. Its important to talk with your doctor about the screening options below, as each person is different.

  • Magnetic resonance imaging An MRI uses magnetic fields to produce detailed images of the pancreas.
  • Endoscopic ultrasound A thin, lighted tube is passed through the patient’s mouth and stomach. The tube goes down into the small intestine to take a picture of the pancreas.

Screening options are likely to change over time as new technologies are developed and more is learned about FPC. Its important to talk with your doctor about screening tests that are right for you. Learn more about what to expect when having common tests, procedures, and scans.

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