Pre-diagnostic levels of anionic trypsinogen, cationic trypsinogen, and pancreatic secretory trypsin inhibitor in relation to pancreatic cancer risk.
OBJECTIVE
Experimental studies have suggested that trypsinogen may enhance tumor progression and that the ratio between anionic trypsinogen and cationic trypsinogen (HAT/HCT) and between the sum of trypsinogens and pancreatic secretory trypsin inhibitor (PSTI) ((HAT + HCT)/PSTI) are disturbed in patients with pancreatic cancer. The aim of this study was to investigate if pre-diagnostic levels of these parameters are associated with subsequent pancreatic cancer risk.


METHODS
A total of 33,346 subjects participated in a health screening programme in Malmö, Sweden. Pancreatic cancer cases (n = 84) were matched to three controls each. HAT, HCT and PSTI were analyzed in pre-diagnostic serum samples. Odds ratios for pancreatic cancer were calculated using logistic regression and were then stratified for other risk factors.


RESULTS
In the main analysis, a statistically significant association between the ratio between HAT/HCT and pancreatic cancer was observed for all, for the crude OR and for the ORs adjusted for sex, BMI or Helicobacter pylori. When stratified for sex, statistically significant associations were found for females in the crude OR and for the ORs adjusted for time to analysis, BMI, alcohol consumption or H. pylori. There was a positive association between the ratio of HAT/HCT to pancreatic cancer in the intermediate/high alcohol consumption group and subjects with a BMI <25. The sum of trypsinogens showed a similar pattern, but was only of borderline significance in the intermediate/high alcohol consumption group.


CONCLUSIONS
Our hypothesis predicted an increased risk for pancreatic cancer related to an imbalance between trypsin activity and trypsin inhibition capacity. The findings concerning the ratio of HAT/HCT are in line with this. The results related to analyses stratified for other risk factors should be considered as mainly explorative.
Johansen
Dorthe
D
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden. dorthe.johansen@med.lu.se
Manjer
Jonas
J
Regner
Sara
S
Lindkvist
Björn
B
D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D000838:Anions; D002412:Cations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000209:etiology*; D011446:Prospective Studies; D020033:Protein Isoforms / Q000097:blood; D012306:Risk; D012907:Smoking / Q000009:adverse effects; D013548:Sweden; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000097:blood*; D014362:Trypsinogen / Q000097:blood*
D000838:Anions; D002412:Cations; D020033:Protein Isoforms; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen