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: Ongoing

Scientific abstract

(View plain language abstract)

Background

Consumption of fat overall and total saturated fatty acids from animal products has been associated with elevated pancreatic cancer risk, but epidemiological studies relating pancreatic cancer to individual fatty acid intakes are scarce and inconsistent. The inconsistency between epidemiological studies may be due to the small number of patients diagnosed with pancreatic cancer and/or the narrow range of fatty acid intakes in these cohorts. In addition, results derived from these studies are mostly based on self-reported food intakes using a food frequency questionnaire. Measurement error in reported dietary habits could have affected results. Finally, food composition tables are incomplete for some fatty acids (trans fatty acids, individual minor fatty acids). Plasma phospholipid measures of some specific fatty acids, non endogenously synthesized, are a more accurate reflection of fatty acid intakes than estimates based on multiple food types determined by questionnaires. However, there is no study conducted so far relating biomarkers of dietary fatty acids to pancreatic cancer risk.

Hypothesis & Objectives

The main hypothesis is that some specific dietary fatty acids – individual saturated fatty acids, industrial trans fatty acids, omega-3 and omega-6 polyunsaturated fatty acids – have an impact on pancreatic cancer risk. Our main objective is to determine pre-diagnostic biomarkers of sixty fatty acids associated to the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Settings & Methods

We will design a case-control study nested within the EPIC cohort among subjects who completed the dietary questionnaire and provided blood samples in ten countries. During the follow-up (September, 2010), 814 subjects (398 men, 416 women) with pancreatic cancer were identified. For each case subject, one matched control (ratio 1:1) will be chosen randomly among cohort subjects without cancer (incidence density matching). Control subjects will be 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 will be determined in plasma phospholipids through optimized and validated 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. Hazard ratios and their 95 % confidence intervals of pancreatic cancer risk associated with levels of fatty acids will be estimated using the Cox proportional regression model. The statistical power will be 0.87 to detect an exposure-disease association equivalent to an expected RR of 1.5 between the extreme quartiles of the population exposure distribution. Finally, we will consider the use of pathways analysis to simultaneously explore a list of relationships between dietary, lifestyle factors and biomarkers of fatty acids, while at the same time evaluate their possible etiological role in pancreatic cancer development.

Impact

Our study based on biomarkers of fatty acids will greatly enhance scientific awareness of the link between individual fatty acids including trans fatty acids and pancreatic cancer risk. This new knowledge will allow to develop more effective public health policies targeted on dietary fatty acids for pancreatic cancer prevention.

Plain language abstract

Background

Consumption of total fat and total saturated fatty acids from animal products has been associated with elevated pancreatic cancer risk, but epidemiological studies relating pancreatic cancer to individual fatty acid intakes are scarce and inconsistent. The inconsistency between epidemiological studies may be due to the small number of patients diagnosed with pancreatic cancer and/or the narrow range of fatty acid intakes in these cohorts. In addition, results derived from these studies are mostly based on self-reported food intakes using a food frequency questionnaire. Measurement error in reported dietary habits could have affected results. Finally, food composition tables are incomplete for some fatty acids (trans fatty acids, individual minor fatty acids). Plasma phospholipid measures of some specific fatty acids are a more accurate reflection of fatty acid intakes than estimates based on multiple food types determined by questionnaires. However, there is no study conducted so far relating biomarkers of dietary fatty acids to pancreatic cancer risk.

Aims & Objectives

Our main objective is to determine biomarkers of dietary exposure to fatty acids associated to the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.How it will be done. We will design a case-control study nested within the EPIC cohort among subjects who completed the dietary questionnaire and provided blood samples in ten countries. During the follow-up (September, 2010), 814 subjects (398 men, 416 women) with pancreatic cancer were identified. For each case subject, one matched control will be chosen randomly among cohort subjects without cancer. Fatty acid concentrations will be determined in plasma phospholipids through optimized gas chromatography methodology set up at IARC, allowing the quantification of 60 fatty acids including 16 trans fatty acid from industrial processes and natural animal sources. Pancreatic cancer risk associated with levels of fatty acids will be estimated using relevant statistical models.

Potential Impact

Our study based on biomarkers of fatty acids will greatly enhance scientific awareness of the link between individual fatty acids including trans fatty acids and pancreatic cancer risk. This new knowledge will allow to develop more effective public health policies targeted on dietary fatty acids for pancreatic cancer prevention.