How does genetics affect the risk of pancreatic cancer?

In those who develop pancreatic cancer, surgery is the best option if it is operable. Additional radiation and/or chemotherapy may improve the appearance of operated patients. For those deemed inoperable, radiation and/or chemotherapy may be used.

Screening for pancreatic cancer in asymptomatic individuals is not particularly advised unless they are in the high-risk group. (Photo: Phynart Studio/E+/Getty Images)

New Delhi: In general, pancreatic cancer can be divided into cancer that arises from the tubes that carry digestive juices from the pancreatic glands (called the exocrine pancreas) to the segment of the small intestine called the duodenum, and this cancer is called Pancreatic Ductal Adenocarcinoma; the other, rarer type are cancers that arise from endocrine cells that reside in the pancreas (called pancreatic islets) such as alpha cells (secreting glucagon), beta cells (secreting insulin), delta cells (secreting somatostatin), and pancreatic polypeptide cells. (secreted pancreatic polypeptide – PP). Cancers arising from the endocrine part of the pancreas are classified as neuro-endocrine tumors.

What are the risk factors of pancreatic cancer?

In an interaction with News9Live, Dr Thangarajan Rajkumar, Director of Research (Oncology), MedGenome, shared insights about pancreatic cancer, its risk factors and how palliative treatment comes to the rescue of patients.

“The main risk factors for pancreatic ductal adenocarcinoma are smoking, alcohol, obesity, chronic pancreatitis and genetic factors. A family history of early-onset pancreatic cancer (<50 years) is associated with a much higher risk of developing pancreatic cancer. Among the genes that have been shown to be genetically altered (genes passed from parents to their offspring) and that may be associated with a much greater risk of developing pancreatic ductal adenocarcinoma include STK11 (screening starting at age 30 years or earlier), p16 (CDKN2A) (screening should begin at age 40 or earlier), BRCA1, BRCA2, TP53, ATM, PALB2, MLH1, MSH2, MSH6 and PMS2 (screening in those who carry a disease that causes mutation in other listed genes can start from 50 years or earlier); The last 4 genes cause mismatched DNA repair abnormalities and result in Lynch syndrome, which has cancers of the large intestine as well as cancers in other areas, including the pancreas. Moreover, the PRSS1 gene is known to be associated with hereditary pancreatitis and it is better for them to start defatting 20 years after pancreatitis or at age 40,” explained Dr Rajkumar.

In individuals suspected of having a possible hereditary cancer, genetic counseling and the subsequent decision to undergo gene testing using a gene panel is advisable. In those with pancreatic cancer and a germline mutation in one of the genes (the list will grow as more research is done), first (parents, siblings, children) and second degree (grandparents, nephews, aunts, relatives (e.g. uncles, nephews and nieces) can be offered predictive testing (after they are over 18), testing only for the identified disease-causing mutation.

Pancreatic cancer screening

Current screening in these individuals at high risk for pancreatic cancer will include the use of imaging modalities such as contrast-enhanced magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP) which evaluates the bile duct inside and outside the liver, gallbladder and pancreas. and its ducts near the head of the pancreas. Using endoscopy-guided ultrasound is another option.

Screening for pancreatic cancer in asymptomatic individuals is not particularly advised unless they are in the high-risk group. A lot of research is going on to develop blood-based tests, which if proven to be accurate, will be very useful.

Palliative care for pancreatic cancer

In those who develop pancreatic cancer, surgery is the best option if it is operable. Additional radiation and/or chemotherapy may improve the appearance of operated patients. For those deemed inoperable, radiation and/or chemotherapy may be used. In individuals with metastatic disease, chemotherapy and targeted therapy may be tried. In patients with advanced disease and mismatched DNA repair gene mutations or high tumor mutational burden, immune checkpoint therapy with Pembrolizumab may be given. Palliative care is important when the cancer has spread and the general condition is poor, with a focus on keeping the patient comfortable and pain-free.

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