Is pancreatic cancer hereditary?

Pancreatic cancer has always been a disease that people are afraid of. Recently, a patient from Hangzhou came to see a doctor because of a mass in the pancreatic body and tail found on CT. After a detailed consultation on the medical history, the attending doctor found that the patient had 3 brothers and 3 sisters, among whom the patient’s eldest brother also died of pancreatic cancer. Considering that this may be a pancreatic cancer family, we recommended that his brothers and sisters undergo a pancreatic thin-layer CT scan. As a result, the patient’s younger brother was also found to have a mass in the pancreatic body and tail. Both patients completed pancreatic body and tail resection in our department, and postoperative pathology confirmed that they both had pancreatic ductal adenocarcinoma. Seeing this, we can't help but ask: Does pancreatic cancer have familial aggregation, and is pancreatic cancer hereditary?

Clinically, pancreatic cancer can be divided into two types according to genetic background, one is familial aggregation and the other is sporadic. Familial pancreatic cancer (FPC) is an established genetic tumor syndrome, accounting for about 3% of all pancreatic cancers. Due to its vertical relationship, it is generally considered to be autosomal dominant inheritance. There has been controversy over the clinical diagnostic criteria for familial pancreatic cancer. Most experts define it as the occurrence of pancreatic cancer with pathological evidence in 2 or more family members in a family without other malignant hereditary tumors. Familial pancreatic cancer was first reported by MacDermott et al. in 1973. In 1991, Ghadirian et al. collaborated with the International Agency for Research on Cancer to find that 7.8% of pancreatic cancer patients had a family history, which was 13 times that of the control group. A positive family history of pancreatic cancer, like smoking, is one of the high-risk factors for pancreatic cancer. In a pancreatic cancer family, the risk increases significantly with the increase in the number of pancreatic cancer patients among first-degree relatives. For example, if one first-degree relative has pancreatic cancer, the risk is 4.6 times that of the general population. If two first-degree relatives have pancreatic cancer, the risk will reach 6.4 times that of the general population. If three or more first-degree relatives have pancreatic cancer, the risk will reach 32 times. In addition, patients with a positive family history of pancreatic cancer in their first-degree relatives will also have an increased risk of malignant tumors in other parts of the body (such as ovarian cancer, breast cancer, lymphoma, and colon cancer). Moreover, familial pancreatic cancer also has an early genetic phenomenon, that is, the younger the generation, the earlier the age of onset, the more severe the symptoms, and the worse the prognosis.

The causes and mechanisms of familial pancreatic cancer are still not fully understood. It is currently believed that the occurrence of familial pancreatic cancer is mainly due to gene mutation and inheritance. Compared with sporadic pancreatic cancer, there is no obvious difference in living habits, diet, age, gender and occupation. With the development of molecular genetics and high-throughput technology, many genes related to familial pancreatic cancer have been discovered. For example: breast cancer susceptibility genes BRCA1 and BRCA2, BRCA2 co-localization genes PALB2, PALLD, CDKN2A, APC and Peutz-Jeghers syndrome genetic genes STK11/LKB1. In addition, for known genetic variations or gene mutations, taking corresponding gene therapy or targeted therapy may provide new hope for improving the prognosis of familial pancreatic cancer.

Family members of familial pancreatic cancer are at high risk of pancreatic cancer. After a relative is diagnosed with pancreatic cancer, family members must not be too nervous, excessive or too frequent examinations, and regular follow-up monitoring is sufficient. There is a special backup registry for familial pancreatic cancer. For families with 2 or more pancreatic cancer patients, you can register and report to the pancreatic surgery department of the cancer hospital. Experts will formulate a reasonable screening measure and time based on the actual situation. Generally speaking, the starting age of screening is around 50 years old, but for family members with pancreatic cancer at the age of less than 50 years old, it should be 10 years lower than the youngest pancreatic cancer onset age (for example, the youngest patient is 45 years old, and other family members should start screening at around 35). Screening methods include ultrasound gastroscopy (EUS), thin-layer spiral CT, MRI, MRCP, endoscopic retrograde cholangiopancreatography (ERCP) and tumor marker CA199. Foreign studies have found that 6.8 percent of relatives of familial pancreatic cancer patients were diagnosed with pancreatic cancer during regular EUS screening, and a number of IPMN (intraductal papillary mucinous neoplasm, a precancerous lesion) and PanIN patients (pancreatic intraepithelial neoplasia, a precancerous lesion) were also found.

Therefore, for the majority of family members who have pancreatic cancer patients among their direct relatives, they should pay attention to their own health, especially the health of the pancreas, and have regular physical examinations and early screening to achieve early diagnosis and early treatment. We have rich experience in the diagnosis, treatment, monitoring and management of familial pancreatic cancer, and have accumulated many classic familial pancreatic cancer cases. Family members of pancreatic cancer patients with related health needs and doubts can come to our outpatient clinic for consultation and treatment.