Biomarkers of dietary fatty acids and risk of pancreatic cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

  • Topic: Pancreatic Cancer
  • Institution: International Agency for Research on Cancer (IARC)
  • Country: France
  • Status: Completed

Scientific abstract

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Background

Since dietary fatty acids have direct tumorigenic effects in animal and in vitro models, specific dietary fatty acids and fatty acid metabolism might be related to pancreatic cancer development. Consumption of fat overall has been associated with elevated pancreatic cancer risk in some epidemiological studies. However, epidemiological studies relating pancreatic cancer to individual fatty acid intakes are scarce and inconsistent.

Objective

To determine the association between pre-diagnostic biomarkers of exposure to fatty acids and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Design

A case-control study nested within the EPIC cohort was designed among subjects who completed the dietary questionnaire and provided blood samples. During the follow-up, 814 subjects (398 men, 416 women) with pancreatic cancer were identified. For each case subject, one matched control was chosen randomly among cohort subjects without cancer. Control subjects were matched to cases for sex, age at blood collection, date and time at blood collection, fasting status, and, for women, use of pill/hormonal replacement treatment. Fatty acid concentrations were determined in plasma phospholipids through gas chromatography methodology set up at IARC, allowing the quantification of 60 fatty acids including 16 trans fatty acid isomers from industrial processes and natural animal sources. Odds ratios and their 95 % confidence intervals of pancreatic cancer risk by tertiles of fatty acids were estimated using conditional logistic regression models. Tertiles of plasma levels of fatty acids were determined on the basis of the distribution among control individuals. The lowest tertile is used as reference category. Tests for linear trends were performed by entering the categorical variable as continuous term in the multivariable models and using the Wald statistic to obtain a P value (Ptrend). All multivariate models were adjusted by sex, date at blood collection, educational attainment, BMI, height, physical activity, alcohol intake, total energy intake, and for women ever use of hormone replacement therapy, and parity and age at first full-term birth combined.

Results

A decreased risk of pancreatic cancer was significantly associated with high levels of heptanoic acid (17:0) from dairy foods (OR for the highest versus lowest tertile [t3-t1]=0.61, 95%CI=0.40-0.94; p for trend=0.025), a-linolenic acid from seeds and nuts (OR [t3-t1]=0.59, 95%CI=0.38-0.90; p for trend=0.020), and docosapentaenoic acid from marine sources (OR[t3-t1]=0.53, 95%CI=0.33-0.86; p for trend=0.010).

Conclusion

Our findings based on specific biomarkers of fatty acids suggest that high intake of dairy foods, seeds and fish might decrease pancreatic cancer development.

Plain language abstract

Background:

Dietary fatty acids are suspected to be involved in pancreatic cancer development. Consumption of total fat may increase pancreatic cancer risk in populations. However, epidemiological studies relating pancreatic cancer to different types of fatty acid are scarce and inconsistent.

Aims and objectives:

To determine the association between blood levels of fatty acids, as biomarkers of dietary fatty acids and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

How the study was carried out:

We designed a case-control study nested within the EPIC cohort among subjects who completed the dietary questionnaire and provided blood samples at baseline. During the follow-up, 814 subjects (398 men, 416 women) with pancreatic cancer were identified. For each case subject, one matched control was chosen randomly among cohort subjects without cancer. Fatty acid concentrations were determined in plasma through gas chromatography methodology set up at IARC, allowing the quantification of 60 fatty acids. Risk of developing pancreatic cancer by levels of different types of fatty acids was estimated using sophisticated statistical models.

Key findings and conclusions:

A decreased risk of pancreatic cancer was significantly associated with high levels of fatty acids derived from dairy foods, from seeds and nuts and fish. These findings suggest that high intake of dairy foods, seeds and fish might decrease pancreatic cancer development. Furthermore, high BMI and smoking might be associated with increased risk of pancreatic cancer, particularly in women.