Metabolic syndrome is linked to the incidence of pancreatic cancer

Abstract

Background: Although previous studies have showed that metabolic syndrome is one of the contributors of pancreatic cancer, there is no clear consensus that early stages of metabolic syndrome are linked to increased incidence of pancreatic cancer. Therefore, we confirmed the linkage between metabolic syndrome and pancreatic cancer, and shown that even early stage of metabolic syndrome is linked to pancreatic cancer in the retrospective observational study.

Methods: We recruited approximately 4.6 million Japanese in 2005 and followed up these subjects for more than 10 years. At the time of the enrollment, after obtaining clinical data with prescribed drugs and examining the presence or absence of metabolic syndrome (MetS), we followed up on these subjects with and without MetS to examine the incidence of pancreatic cancer. The modified criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII) were used to define MetS.

Findings: During the 40.7-month average follow-up period for 2,707,296 subjects with complete data for identifying MetS and important risk factors without pancreatic cancer before the enrollment, 87,857 suffered from pancreatic cancer. Pancreatic cancers occurred in 16,154 of 331,229 subjects (4.9%) in the MetS group and 71,703 of 2,376,067 patients (3.0%) in the non-MetS group (hazard ratio (HR), 1.37; 95% confidence interval [CI], 1.34-1.39; p < 0.0001 after the adjustment with age, smoking and sex). As the number of the constituent factors of MetS increased from one to five, the incidence of pancreatic cancer correspondingly increased (HR: 1.11, 1.23, 1.42, 1.66 and 2.03 using Cox proportional hazard models, p < 0.0001 each). When we defined MetS using the Japanese criteria, the results are in accord with the results using NCEP/ATPIII. Especially pre-metabolic syndrome (pre-MetS) in the Japanese criteria was tightly linked to the incidence of pancreatic cancers.

Interpretation: MetS is confirmed to be linked to pancreatic cancer. Although we cannot conclude causality. We also demonstrated the link between pre-MetS and pancreatic cancer.

Funding: The sponsors of the study were Japanese Heart Foundation and Japan Cardiovascular Research Foundation. This is also partially supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and Grants-in-Aid from the Japan Agency for Medical Research and Development.

Keywords: Big data; Early stage of metabolic syndrome; Metabolic syndrome; Pancreatic cancer; Prevention of metabolic syndrome.

Fig. 1

The consort diagram for the selection of the enrolled subjects.

Fig. 2

Kaplan–Meier curves for the incidence of the pancreatic cancer with and without MetS (A) and for the incidence of pancreatic cancer among the six groups with 0–5 components of MetS (B) based on the modified criteria of NCEP/ATPIII.

Fig. 2

Kaplan–Meier curves for the incidence of the pancreatic cancer with and without MetS (A) and for the incidence of pancreatic cancer among the six groups with 0–5 components of MetS (B) based on the modified criteria of NCEP/ATPIII.

Fig. 3

HRs for the incidence of the pancreatic cancer with and without MetS (A) and for the incidence of pancreatic cancer among the six groups with 0–5 components of MetS (B) based on the modified criteria of NCEP/ATPIII. (A) HR is 1.37 (95% CI, 1.34–1.39; p < 0.0001). (B) When factors of MetS increase from 1 to 5, HR increased to 1.11 (95% CI, 1.09–1.12; p < 0.0001), 1.23 (95% CI, 1.20–1.25, p < 0.0001), 1.42 (95% CI, 1.39–1.45, p < 0.0001), 1.66 (95% CI, 1.61–1.72, p < 0.0001), and 2.03 (95% CI, 1.90–2.17, p < 0.0001), respectively.

Fig. 4

Kaplan–Meier curves of MetS-free and MetS-developed groups, and MetS-recovered and MetS-persistent groups for the incidence of pancreatic cancer.

Fig. 5

Kaplan–Meier analysis without the subjects with pancreatic cancer detected in 3 years after the entry.

Fig. 6

Kaplan–Meier curves for the incidence of the pancreatic cancer with preMetS or MetS with 2 or 3 factors (A) and for the incidence of pancreatic cancer among the eight groups with any combination of the three components of MetS (B) based on the Japanese criteria for MetS.

Fig. 6

Kaplan–Meier curves for the incidence of the pancreatic cancer with preMetS or MetS with 2 or 3 factors (A) and for the incidence of pancreatic cancer among the eight groups with any combination of the three components of MetS (B) based on the Japanese criteria for MetS.

Fig. 7

HRs for the incidence of the pancreatic cancer with and without MetS (A) and for the incidence of pancreatic cancer among the eight groups with any combination of the three components of MetS (B) based on the Japanese criteria for MetS. (A) HRs of preMetS, MetS with 2 factors, and MetS with 3 factors are 1.14 (95% CI, 1.12–1.17; p < 0.0001), 1.27 (95% CI, 1.24–1.29; p < 0.0001), and 1.45 (95% CI, 1.41–1.49; p < 0.0001), respectively. (B) the independent factor or combinations of constituting factors for MetS increased HRs in the groups of dyslipidemia (DL, 0.98 (95% CI, 0.93–1.04), p = 0.48), hypertension (HT) with DL (0.96 (95% CI, 0.90–1.01), p = 0.14), HT (0.93 (95% CI, 0.89–0.98), p < 0.0001), high blood glucose levels (HGS) (1.27 (95% CI, 1.24–1.30), p < 0.0001), DL with HBS (1.39 (95% CI, 1.35–1.44), p < 0.0001), HBS with HT (1.26 (95% CI, 1.23–1.29), p < 0.0001) and HBS with HT and DL (1.45 (95% CI, 1.41–1.49), p < 0.0001).