Metabolic syndrome linked to higher pancreatic cancer risk, study shows

By Pooja Toshniwal PahariaReviewed by Sophia CoveneyDec 17 2023

In a recent study published in the journal eClinicalMedicine, researchers investigated the association of metabolic syndrome (MetS) with pancreatic cancer.

Background

Cancer and cardiovascular disorders are significant burdens on individuals and economies worldwide. Due to new imaging techniques and biomarkers, early diagnosis has become more feasible and helped to combat cancer.

Pancreatic tumors are often considered the most fatal cancers due to similar incidence and death rates. Prevention and prompt diagnosis of pancreatic cancer are difficult, leading to diagnostic delays and the inability to treat it comprehensively.

MetS, a group of medical disorders that enhance cardiovascular disease, stroke, and type 2 diabetes (T2D) risks, has been associated with pancreatic tumors. However, a clear consensus has not been attained on the link or whether an initial stage of MetS (pre-MetS) is associated with increased pancreatic cancer incidence.

About the study

In the present observational retrospective study, researchers investigated whether MetS increased pancreatic cancer risk.

The researchers analyzed health insurance claims from the Japan Medical Data Center (JMDC). The data included 4,600,443 individuals insured from 2005 to 2020. The database included health insurance claims of general staff and their families and medical therapies administered to the insured individuals.

The team obtained clinical data, including drug prescriptions, and investigated MetS presence at enrolment. To examine pancreatic cancer incidence, they followed individuals with MetS presence and absence for >10 years.

The researchers used Cox proportional hazard models to determine the hazard ratios (HRs), adjusting for age, sex, and smoking. They defined MetS using the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII) criteria and pancreatic cancer using the International Classification of Diseases, tenth revision (ICD-10) codes.

The NCEP/ATPIII defines MetS as cases with three or more of these factors: (i) serological triglycerides (TG) ≥150 mg/dL (or 1.7 mmol/L); (ii) high-density lipoprotein cholesterol (HDL) below 40 mg/dL (or 1.0 mmol/L) for males and 50.0 mg/dL (or 1.3 mmol/L) for females; (iii) fasting glucose ≥110 mg/dL (or 6.1 mmol/L) and non-fasting glucose ≥140 mg/dL (or 7.8 mmol/L), or on medication; (iv) blood pressure 130/85 mm of Hg or higher or antihypertensive drug use; and (v) body mass index (BMI) 25 kg/m² or higher.

The Japanese MetS criteria requires abdominal obesity, as indicated by abdominal circumference at the umbilical level of ≥85 cm in males and ≥90 cm in females with two or more of these factors: (i) increased triglycerides or decreased high-density lipoprotein cholesterol, (ii) elevated blood pressure, and (ii) elevated fasting blood glucose levels. Central abdominal obesity with either of the factors was described as pre-MetS. The researchers excluded T2D patients from the analysis. In addition, they eliminated 1,825,660 individuals with inadequate clinical data and 42,885 individuals without observation period data.

Results

During the mean follow-up of 41 months for 2,707,296 individuals with sufficient data for MetS identification and risk factors without pancreatic cancer at enrolment, 87,857 developed pancreatic cancer. Pancreatic cancers were reported in five percent (16,154 out of 331,229) of MetS individuals and three percent (71,703 out of 2,376,067) of non-MetS group individuals (HR, 1.4).

With an increase in MetS components from one to five, pancreatic cancer incidence increased, with corresponding HR values of 1.1, 1.2, 1.4, 1.7, and 2.0, respectively. The Japanese criteria for MetS yielded similar results. Pre-MetS, as determined using the Japanese criteria, was strongly associated with pancreatic cancer incidence. Excluding individuals with pancreatic cancer identified within three years of study enrolment, an HR value of 1.4 was obtained compared to non-MetS individuals. 

Subgroup analyses on 206,847 individuals analyzed the impact of metabolic changes on pancreatic cancer occurrence. The study categorized participants into four groups based on MetS presence or absence: two sub-groups with metabolic syndrome from 2010 to 2011 with the presence or absence of metabolic syndrome from 2012 to 2013, and the remaining two sub-groups without metabolic syndrome from 2010 to 2011 with MetS presence and absence from 2012 to 2013.

MetS individuals were classified as metabolic syndrome-recovered and metabolic syndrome-persistent groups, while those without MetS were classified as metabolic syndrome-developed and metabolic syndrome-free groups. The study found that changes in MetS status significantly impacted pancreatic cancer occurrence, with HRs of the MetS-free and MetS-developed groups being 1.0 and 1.4, respectively.

Conclusions

Overall, the study findings confirmed the association between MetS (including pre-MetS) and the incidence of pancreatic tumors. However, causality could not be concluded.

Pancreatic cancer incidence is known to be linked to T2D, chronic pancreatitis, and smoking. Taken together with the present study findings, researchers endorse MetS prevention and treatment as preventive strategies to lower the incidence of pancreatic tumors.