Biomarkers of industrial trans fatty acids and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

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

Scientific abstract

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Background

The relationship between specific trans fatty acids and health is still of major concern. Industrial trans fatty acids (ITFAs) occur in hydrogenated vegetable oils, used as ingredients in industrially processed foods to prevent oxidative rancidity, and a high consumption of these specific foods has been consistently associated with increased risk of cardiovascular disease. Few data is available regarding the potential deleterious effect of ITFAs on cancer risk.

Methods

In order to bring more evidence on the effects of trans fatty acids on breast cancer risk, including ITFAs and natural trans fatty acids from animal sources, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, among women who completed the baseline dietary questionnaire and provided blood samples. This study includes 4,852 invasive breast cancer cases. Control women were matched to cases on age, menopausal status, centre and date of blood collection. Plasma phospholipid fatty acid concentrations were measured through improved gas chromatography methodology, allowing the separation, identification and quantification of trans fatty acid isomers from industrial processing and from animal sources. A conditional regression model adjusted for risk factors of breast cancer was used to estimate the association between biomarkers of fatty acids and breast cancer risk. Statistical analysis was run within the French arm of the EPIC study.

Results

In a preliminary statistical analysis of the French arm of EPIC, involving 700 breast cancer cases, positive association was found between breast cancer risk and the ratio of monounsaturated to saturated fatty acids, suggesting that a high intake of saturated fatty acids along with an increased hepatic desaturation of saturated fatty acids may increase breast cancer risk. A significant positive association was found between breast cancer risk and ITFA isomers, while no significant association was found with trans fatty acid isomers from natural animal sources. These data suggest that a high intake of ITFAs may increase breast cancer risk, while natural trans fatty acids may not. Finally, no significant association was found between breast cancer risk and plasma phospholipid ω-6 and ω-3 polyunsaturated fatty acid levels. The null association reported for ω-3 polyunsaturated fatty acids may suggest that a minimal intake is required to allow a protective effect on breast cancer. These data will be refined by the investigation of the association with breast cancer in the entire EPIC cohort, as soon as databases will be completed.

Plain language abstract

Hypothesis

Our hypothesis was that a high intake of industrial trans fatty acids (ITFAs) might increase risk of breast cancer.

Background

Some epidemiological studies suggest that a high intake of ITFAs could increase breast cancer risk. However, data are still discrepant. Epidemiological studies are limited by the difficulty to obtain an accurate estimation of dietary fat through food-frequency questionnaires. Thus, the use of biomarkers could be a more successful approach to investigate the association between ITFAs and breast cancer risk. In our first French study based on biomarkers, we found evidence that women with high blood levels of ITFAs had a twofold increased risk of breast cancer compared to those with low blood levels, but no data was available regarding natural TFAs from animal sources. The objective of our study was to investigate the association between blood levels of trans fatty acids and breast cancer risk in the European EPIC cohort.

Methods

Design
The EPIC study is an on-going multi-centre study designed to investigate the relationship between diet or dietary habits, nutrition, lifestyle and environmental factors and the incidence of cancer of various sites. The total EPIC cohort includes 519,978 participants. The main age range of the participants was from 35 – 70 years.

Nested case-control study
For this project, we designed a case-control study nested within the EPIC cohort among women who completed the dietary questionnaire and provided blood samples in ten countries. During the follow-up, 4,852 women with invasive breast cancer were identified. Control subjects without cancer were matched to case subjects on age, menopausal status at recruitment, recruitment center, and recruitment date.

Fatty acid analyses
Plasma phospholipid fatty acid levels have been determined according to an improved methodology through gas chromatography, allowing a complete separation of ITFAs from natural trans fatty acids. So far, measurements of fatty acids and preparation of databases have been completed for France, UK, Greece, Italy, the Netherlands and Spain.

Statistical methods
In order to evaluate the association between fatty acids and cancer risk, hazard ratios and their 95 % confidence intervals were estimated using a conditional regression model adjusted for risk factors of breast cancer. So far, statistical analysis have been completed within the French arm of the EPIC cohort.

Key findings

Within the French arm of the EPIC cohort, we found a positive association between breast cancer risk and levels of industrial trans fatty acid isomers, while no association was found for trans fatty acids from animal source. These data suggest that a high intake of industrial trans fatty acids may increase breast cancer risk.

Grant publications