What Is Pancreatic Cancer?
It is a cancer of the pancreas, and it is considered the most challenging of all cancers because of its hereditary nature. Genes and family history play an important role. This cancer is the leading cause of death. Individuals with a family history of pancreatic cancer are at an increased likelihood of developing the disease during their lifetime.
What Is Hereditary and Familial Pancreatic Cancer?
The presence of pancreatic cancer within a family elevates the susceptibility of its members and descendants to the disease due to genetic mutations. Consequently, a recognizable family medical history plays a crucial role in the treatment and outlook of pancreatic cancer.
What Is the Difference Between Hereditary Pancreatic Cancer and Familial Pancreatic Cancer (FPC)?
-
Hereditary Pancreatic Cancer: Hereditary Pancreatic Cancer refers to a specific category of pancreatic cancer that is linked to genetic factors. In this context, individuals who carry certain genetic mutations have a notably higher risk of developing pancreatic cancer compared to the general population. Understanding the genetic basis of hereditary pancreatic cancer allows for enhanced surveillance and management strategies. Individuals identified as having a higher risk may undergo more frequent screening tests to detect any potential cancer development at an early and treatable stage. Moreover, risk-reducing surgeries (such as removing the pancreas) might be considered in extreme cases.
-
Familial Pancreatic Cancer: It is defined as a family having at least one pair of the first generation (either parent-child or sibling of same parents) with pancreatic cancer without any identifiable syndrome in the family. Relatives of the family with familial pancreatic cancer show an increased risk of pancreatic cancer compared to the general population. This also depends on their relationship with their first generation. Smoking is one of the important factors that increases the risk of familial pancreatic cancer and reduces the age of onset of cancer, and the decrease can be up to ten years.
Can Surveillance Methods Detect Early Pancreatic Cancer?
Pancreatic cancer is fatal because of its early metastases and its rapidly progressive nature. Surgical excision is the current and best treatment option. Relatives at risk must undergo a surveillance warrant for pancreatic cancer. Surveillance must start at an early age and can be done with the help of endoscopic ultrasound or MRI (magnetic resonance imaging). These diagnostic tests help in the early detection of cancer compared to CT (computed tomography).
What Are the Genes Responsible for Pancreatic Cancer?
Mutations (changes) in inherited genes are seen in patients with hereditary pancreatitis and inherited cancer syndromes. Pancreatic cancer is significantly influenced by genetic factors, as evidenced by the discovery of germline mutations in various genes that contribute to both hereditary and familial forms of the disease. These genes are BRCA1 (Breast Cancer Gene 1), BRCA2 Breast Cancer Gene 2, PALB2 (Partner and Localizer of BRCA2), ATM (Ataxia Telangiectasia Mutated), CDKN2A (Cyclin-Dependent Kinase Inhibitor 2A), MLH1(MutL Homolog 1) and STK11 (Serine/Threonine Kinase 11).
What Are the Inherited Syndromes That Are Associated With Pancreatic Cancer?
-
Hereditary Breast-Ovarian Cancer Syndrome: A genetic condition characterized by a higher susceptibility to breast cancer through autosomal dominant inheritance (55 percent), ovarian cancer (39 percent), and other cancers such as the pancreas, male breast, and melanoma.
-
Ataxia Telangiectasia: This is a rare autosomal recessive condition affecting the nervous and immune systems, and its association with pancreatic cancer was seen in BXPC-3 cells (a cell line derived from human pancreatic cancer cells utilized for investigating pancreatic adenocarcinomas and potential therapeutic approaches).
-
Familial Atypical Multiple Mole Syndrome: CDKN2A (a cell cycle regulator gene), codes for P16 protein; this gene affects melanoma and increases pancreatic risk.
-
Familial Adenomatous Polyposis: Also called gastrointestinal adenomas (stomach polyps that are likely to become cancerous).
-
Lynch Syndrome: It is a hereditary condition associated with colorectal cancer and characterized by a lack of polyp formation. It is one of the most common causes of inherited colon cancer. Hence, patients with Lynch syndrome show symptoms of colon cancer and also extra colonic cancers like ovarian cancer, pancreatic cancer, and gastric cancer.
-
Hereditary Pancreatitis: It is rare among cancer predisposition conditions. It is a form of chronic pancreatitis (inflammation of the pancreas) that causes diabetes, pancreatic dysfunction, and increased pancreatic risk.
-
Peutz-Jeghers Syndrome: Pancreatic cancer risk is identified as a 132-fold increase in patients with Peutz-Jeghers syndrome and is caused by mutations in genes. Symptoms include mucocutaneous hyperpigmentation and gastrointestinal polyposis.
How to Assess the Risk and Perform Genetic Counseling?
Identifying patients with pancreatic cancer and conducting a risk assessment for inherited factors in their family members is complex. Some of the risk assessment tests are:
-
Pedigree Analysis: It is a diagrammatic flow chart showing genetic relations among individuals; this can give genetic information.
-
Molecular Tumor Studies: This is a laboratory test where a blood or fluid sample is tested to check for certain genes, proteins, or molecules for a particular disease or condition.
-
Germline Mutation Testing: This is done to detect hereditary mutations that increase the susceptibility to cancer. This is done with a blood, saliva, and cheek swab sample. Again, the intention is for early diagnosis of certain types of cancer.
-
Endoscopic Ultrasound: It is an invasive procedure to assess any abnormality in the digestive tract.
-
Endoscopic Retrograde Cholangiopancreatogram (ERCP): A procedure that uses both upper gastrointestinal endoscopy and X-rays to detect diseases in the bile ducts and pancreas.
In addition to the tests mentioned above, a thorough family history helps identify healthy relatives at high risk of cancer.
Can Surveillance Methods Detect Early Pancreatic Cancer?
High-risk groups such as those with inherited cancer syndromes and familial pancreatic cancers have an elevated risk of developing pancreatic cancer. Therefore, conducting early screening tests aims to detect pancreatic lesions that can be treated.
Two such lesions that help in early detection are:
-
Intraductal Papillary Mucinous Neoplasms (IPMN): These are mucin-producing neoplasms arising from main or sub-branches of pancreatic ducts. They are grossly visible.
-
Pancreatic Intraepithelial Neoplasia (PanIN): It is a non-invasive microscopic neoplasm involving diameter ducts less than 5 to 10 mm (millimeters). These, when left untreated, develop into invasive pancreatic cancers.
Screening tests like endoscopic ultrasounds are done, and treatment is carried out before they become invasive cancers.
Conclusion:
Identifying the relatives of pancreatic cancer patients, and conducting cancer surveillance programs such as intensive medical regimens and yearly colonoscopies, followed by comprehensive risk assessment and genetic counseling, would ideally decrease the fatal rate in pancreatic cancer patients and their families.
