Pancreatic cancer, also known as pancreatic adenocarcinoma, is an aggressive cancer and is the seventh leading cause of cancer-related deaths in the world. The majority of patients diagnosed with pancreatic cancer are in an advanced stage with curative surgery at diagnosis possible in only 10 to 20 percent of patients.
The 5-year survival for this cancer has only improved marginally over the past decade, Dr. Hemanth G N, Consultant – Surgical Oncology & Robotic Surgery, Manipal Hospital Old Airport Road told Financial Express.com.
“There have been no major advances in systemic therapy for advanced pancreatic adenocarcinoma. Only, PARP (Poly ADP ribose polymerase) inhibitors have been added in the treatment of metastatic pancreatic adenocarcinoma with deficiencies in homologous recombination repair of double-stranded DNA breaks (e.g., BRCA 1 & BRCA 2),” Dr. Hemanth said.
This makes it very important to identify patients at high risk of pancreatic ductal adenocarcinoma early enough and test them adequately for improved treatment outcomes, he said.
Family History: Greatest Risk Factor of Pancreatic Cancer
A strong family history is considered the greatest risk factor for pancreatic cancer. Family history of cancer in first- and second-degree relatives is the most relevant.
“Approximately 10 to 15% of pancreatic cancers are familial, which is defined as a family history involving at least 2 first-degree relatives. But, sadly it has been so far possible to discover only 5 % of genetic defects underlying familial pancreatic cancer. An early age of onset of cancer is also associated with an increased likelihood of a hereditary component,” Dr. Hemanth told Financial Express.com.
There are a few disorders that are linked to a predisposition to pancreatic ductal adenocarcinoma such as Hereditary Breast and Ovarian Cancer (HBOC) due to BRCA 2 gene mutation, leading to a 5% lifetime risk of pancreatic cancer.
He also highlighted that the highest lifetime risk of pancreatic cancer, which stands at 40%, is associated with a condition called Inherited Pancreatitis.
“Individuals diagnosed with Peutz Jeghers Syndrome and Familial Atypical Multiple Mole Melanoma Syndrome are also at high risk (15 to 30%) of developing pancreatic ductal adenocarcinoma in their lifetime. Other disorders where genetic testing for hereditary pancreatic cancer should definitely be considered are Ataxia Telangiectasia and a first-degree relative with pancreatic cancer,” he told Financial Express.com.
The risk of pancreatic cancer increases with the number of affected first-degree relatives, with up to 40% risk if 3 first-degree relatives are affected. If 2 first-degree relatives are affected by either of these factors, then the risk of developing pancreatic cancer is around 10%. “Increased risk of pancreatic adenocarcinoma is also observed in patients with mutations of CDKN2A, TP 53, MLH 1, BRCA 2, BRCA 1, and ATM,” he added.
When Should You Consider Genetic Testing?
With low overall incidence (which stands at 5.7 cases per 100,000 person-years) and lack of accurate diagnostic tests, widespread general population-based screening isn’t currently possible, Dr. Hemanth highlighted.
“Genetic testing for hereditary cancer syndromes can identify individuals at high risk for pancreatic cancer or other types of cancer, who could benefit from cancer monitoring. However, due to the large variety of cancer syndromes associated with pancreatic cancer, the identification of individuals eligible for genetic testing is complex. A three-generation pedigree is a gold standard for the evaluation of autosomal inherited disorders and should include specific types of tumours and the age of the patients at diagnosis,” he told Financial Express.com.
Screening for pancreatic cancer is recommended for individuals with the above risk factors around 50 years of age or 10 years before the youngest age of diagnosis in a family member.
Additionally, regular screening with gene testing, blood tests, ultrasound, and MRI in these high-risk individuals can help in the early detection of pancreatic ductal adenocarcinoma.
“It is important for healthcare providers to know any information regarding ethnicity while obtaining a family history, as that may be relevant to specific cancer syndromes of interest. For instance, we have observed that individuals from Ashkenazi Jewish ancestry have a higher incidence of BRCA1/2 mutations than the general population,” he added.