Pancreatic cancer incidence has doubled over the past two decades. Rates are highest in North America and Europe, and within the United States, pancreatic cancer occurs more frequently in Black individuals than in White or Asian populations.

Diagnosing this increasingly prevalent cancer is notoriously difficult, making it essential to identify the key risk factors that contribute to its development. Fortunately, in recent years there has been extensive research into the causes of pancreatic cancer, including many of the studies linked below, which are well worth reading in full.

Here are the top 10 risk factors for pancreatic cancer that are consistently reported across the literature. Clinicians should keep these in mind during routine patient care and provide education about lowering risk.

Smoking

As one of the strongest modifiable risk factors, smoking is associated with an odds ratio of 1.74, meaning that smokers are nearly twice as likely to develop pancreatic cancer than nonsmokers. However, smoking cessation lowers this risk over time. After 10-20 years of abstinence, the risk approaches that of never-smokers.

Alcohol Consumption

Heavy alcohol use (defined as more than three drinks per day) has been associated with an increased risk for pancreatic cancer in multiple studies and meta-analyses. Although light or moderate drinking has not consistently shown a statistically significant association, alcohol is a well-established cause of pancreatitis, which itself markedly increases pancreatic cancer risk. Thus, it is always advisable to limit alcohol intake.

High BMI

Obesity (BMI >30 kg/m²) is an independent risk factor for pancreatic cancer, even after controlling for smoking status, diabetes, and age.

Diabetes

Diabetes is a risk factor worth being mindful of, especially in patients with new-onset diabetes or a sudden worsening of glycemic control later in life. Although the overall risk of developing pancreatic cancer in the setting of new onset diabetes remains low (0.3%-1%), such clinical changes warrant further evaluation.

Dietary Patterns (Red Meat and Sugary Beverages)

Data on red meat and sugar-sweetened beverages are mixed, in part because of confounding factors such as BMI. For example, some studies suggest increased risk in those consuming more than two sugary beverages per day, while others do not. Conversely, healthy diets rich in plant-based foods, nuts, and Mediterranean-style eating patterns have been shown to decrease the risk for pancreatic cancer and should be encouraged.

Pancreatitis

Pancreatitis can both be the cause and a consequence of pancreatic cancer. The risk is particularly elevated within the first year after an episode of pancreatitis, with reported odds ratios of up to 21.35. Although pancreatitis is relatively uncommon, it is important for clinicians to keep this in mind when evaluating for pancreatic cancer or evaluating patients with a history of pancreatitis, and to counsel patients to avoid known triggers of pancreatitis such as alcohol.

Age

Pancreatic cancer risk increases after age 40 and rises with advancing age, with more than 80% of cases developing between age 60 to 80 years. However, the disease is rare in younger individuals.

Family History of Pancreatic Cancer

As with many other cancers, having a close family relative with pancreatic cancer increases the risk. Individuals with family history of pancreatic cancer are recommended to undergo screening magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS).

Genetic Predisposition

Pathogenic variants in genes such as BRCA2 and ATM are associated with a higher risk of developing pancreatic cancer. Individuals with known hereditary cancer syndromes should undergo pancreatic cancer screening with MRCP or EUS. For more detailed information on high-risk genes, please refer to my previous commentary on pancreatic cancer screening.

Premalignant Pancreatic Lesions

Mucinous pancreatic cysts, including mucinous cystic neoplasia (MCN) and intraductal papillary mucinous neoplasm (IPMN), are considered premalignant lesions that may progress to pancreatic cancer. Management depends on the lesion size, growth, and other features, with options ranging from surgical resection to surveillance with MRCP or EUS.

Pancreatic cancer is often considered one of the deadliest malignancies because it is often discovered at an advanced stage. Rather than reacting to the disease after it develops, clinicians should take a proactive approach by focusing on prevention, educating patients about risk factors, and maintaining vigilance with appropriate pancreatic cancer screening.