Spotlight on pancreatic cancer risk

Recent studies assessed how use of dihydropyridine calcium-channel blockers, sustained exposure to hyperglycemia, recurrence of acute pancreatitis, and a range of dietary patterns may influence pancreatic cancer risk.

Several studies published in the past month focused on factors associated with pancreatic cancer risk.

The first, a large, population-based cohort study, found that dihydropyridine calcium-channel blockers were not associated with an increased risk of pancreatic cancer compared with thiazide diuretics. Researchers used the UK Clinical Practice Research Datalink to identify new prescriptions issued by primary care physicians between 1990 and 2018, with follow-up until 2019. They estimated hazard ratios (HRs) for pancreatic cancer among users of dihydropyridine calcium-channel blockers compared with thiazide diuretics and weighted models using standardized morbidity ratio weights based on calendar time-specific propensity scores. Results were published Dec. 14 by the Journal of the American Heart Association.

The cohort included 344,480 initiators of dihydropyridine calcium-channel blockers and 357,968 initiators of thiazide diuretics, generating more than 3.3 million person-years of follow-up. After a median follow-up of 4.5 years, the weighted incidence rate of pancreatic cancer per 100,000 person-years was 37.2 (95% CI, 34.1 to 40.4) for dihydropyridine calcium-channel blockers and 39.4 (95% CI, 36.1 to 42.9) for thiazide diuretics. Overall, dihydropyridine calcium-channel blockers were not associated with an increased risk of pancreatic cancer (weighted HR, 0.93; 95% CI, 0.80 to 1.09), with secondary analyses yielding similar results. The database does not contain information on dispensation of medications, among other limitations, the study authors noted. “Given the long-term use of [dihydropyridine calcium-channel blockers] in patients with hypertension, this observational study provides much needed evidence, as well as reassurance to physicians and patients, regarding the safety of this drug class with respect to pancreatic cancer,” they concluded.

The second study found that the incidence of pancreatic cancer increased significantly with sustained hyperglycemia exposure. Researchers used the National Health Insurance Service Database of Claims to assess how much cumulative hyperglycemia exposure increases pancreatic cancer risk among more than 3.1 million individuals who underwent four consecutive annual health screenings between 2009 and 2013. They defined hyperglycemic burden using a score from 0 to 4, with one point assigned for each time blood glucose level was 100 mg/dL or greater or use of an antidiabetic drug. They also performed semiquantitative scoring of a prediabetic (100 to 125 mg/dL; 1 point) and a diabetic glucose level (≥126 mg/dL; 2 points) and categorized patients into one of nine groups by hyperglycemic score (0 to 8). Results were published Dec. 9 by Diabetes Research and Clinical Practice.

During a median 6.2 years of follow-up, patients with a hyperglycemic burden of 1, 2, 3, and 4 had a 15%, 30%, 26%, and 67% increased risk of pancreatic cancer compared with those with glucose level in a normal range. Risk of pancreatic cancer increased gradually with hyperglycemic burden score, and those with a score of 8 had an 89% higher risk than those in the reference group. Even in those without diabetes, the presence of hyperglycemia at one to three of the check-ups or all four check-ups was associated with increases of about 20% (adjusted hazard ratio [HR], 1.17; 95% CI, 1.09 to 1.24) and about 30% (adjusted HR, 1.28; 95% CI, 1.14 to 1.44) in pancreatic cancer risk, respectively. The researchers did not compare pancreatic cancer incidence between individuals who developed hyperglycemia and those who initially had hyperglycemia but then showed improved blood glucose levels, among other limitations.

The third study found an increased long-term risk of pancreatic ductal adenocarcinoma (PDAC) after acute pancreatitis, which increased with the number of episodes of acute pancreatitis. The retrospective study used a nationwide Veterans Administration database spanning 1999 to 2015. Researchers applied a two-year washout period to exclude patients with pre-existing acute pancreatitis and PDAC. The primary outcome was pancreatic cancer, defined based on one or more primary or secondary diagnosis codes for adenocarcinoma of the pancreas (inpatient or outpatient). The researchers estimated PDAC risk in patients with acute pancreatitis, those with both acute and chronic pancreatitis, and those with chronic pancreatitis alone and compared PDAC risk with those in a control group. Results were published Dec. 20 by the American Journal of Gastroenterology.

The final cohort included more than 7.1 million individuals, 35,550 with acute pancreatitis and 16,475 with PDAC. Cumulative PDAC risk three to 10 years after acute pancreatitis was higher than in controls (0.61% vs. 0.18%; adjusted HR, 1.7 [95% CI, 1.4 to 2.0]; P<0.001). The adjusted HR was 1.5 in the acute pancreatitis group, 2.4 in the chronic pancreatitis group, and 3.3 in the group with both acute and chronic pancreatitis. PDAC risk increased with the number of acute pancreatitis episodes; however, elevated PDAC risk after acute pancreatitis was not influenced by the etiology of acute pancreatitis (gallstones, smoking, or alcohol use). The cohort only represents U.S. veterans, and the study was limited by its retrospective design and use of administrative data, the authors noted.

The fourth study, published on Dec. 2 by Medicine, found that certain dietary patterns are associated with reduced risk of pancreatic cancer among adults. Researchers used a case-control design to assess the influence of several dietary patterns on the risk of pancreatic cancer among newly diagnosed patients in Jordan between March 2015 and August 2018. The ratio of cases to controls was about 1:3, with 101 patients with a medical report confirming the diagnosis of pancreatic cancer and 314 individuals who were not diagnosed with any cancer and were selected from the community. The researchers enrolled cases from four hospitals, one of which was an oncology center. They obtained the data through personal and physical activity questionnaires and a food frequency questionnaire. The questionnaires were completed by trained nutritionists using a face-to-face interview technique.

The study assessed four dietary patterns and their corresponding odds ratios (ORs) of pancreatic cancer cases and controls, represented by quartiles of factor scores: a “Western” dietary pattern, which had the greatest amounts of beer, wine, roasted lamb, meat, chicken sandwiches, beefsteak, and fried fish; a “Traditional” dietary pattern, emphasizing fresh fruits, vegetables, milk, yogurt, and lentils; a “High-Fruit” dietary pattern emphasizing strawberries, melons, watermelon, and other fruit; and a “Soup” dietary pattern emphasizing vermicelli soup, vegetable soup, lentil soup, and mushroom soup. There was a significant reduction in the adjusted risk of pancreatic cancer associated with following a “Traditional” diet at the third and fourth quartiles (ORs, 0.417 [95% CI, 0.206 to 0.843] and 0.215 [95% CI, 0.095 to 0.486], respectively) and a “High-Fruit” diet at the first, second, and third quartiles (ORs, 0.381 [95% CI, 0.194 to 0.749], 0.246 [95% CI, 0.120 to 0.504], and 0.181 [95% CI, 0.083 to 0.394], respectively). The “Soup” dietary pattern showed this protective effect at the third quartile only (OR, 0.159 [95% CI, 0.066 to 0.379]). Finally, the “Western” diet showed a nonsignificant risk of developing pancreatic cancer at any level. The study was subject to possible recall bias and estimation errors, among other limitations, the authors noted. “Our findings support the notion that consuming dietary patterns rich in plant sources, including fruits, vegetables, and legumes, is a wise choice that would contribute to a lower risk of [pancreatic cancer] associated with higher nutrient density and better diet quality,” they concluded.