Erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers and fatty acid synthase: a nested case-control study

Abstract

Background

Previous studies of fatty acids and breast cancer risk have shown mixed results, which may be due in part to tumor heterogeneity. Prior research has also illustrated an important role of specific fatty acids in immune regulation, T cell function, and inflammation, indicating that the effects of specific fatty acids on breast cancer risk may vary by tumor expression of immuno-inflammatory markers. We therefore aimed to evaluate the relationships between prediagnostic erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers (CD4, CD8, CD20, CD163, COX-2) and fatty acid synthase (FAS).

Methods

We conducted a matched case-control study nested within the Nurses’ Health Study II (n = 235 cases and 235 controls). Blood samples were collected from 1996 to 1999. Tumor tissue blocks were collected for cases diagnosed after blood collection and through 2006. Unconditional nominal polytomous logistic regression adjusted for matching factors and potential confounders was used to assess whether associations between fatty acids and breast cancer risk varied by tumor expression subtype, ascertained via immunohistochemistry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated separately by tumor expression subtype using unconditional logistic regression.

Results

Associations between fatty acids and breast cancer risk did not vary substantially by tumor CD4, CD20, CD163, or COX-2. However, n-3 polyunsaturated fatty acids (PUFAs) were inversely associated with CD8^low but not CD8^high cancers (CD8^low OR_{T3 vs T1} = 0.45, 95% CI 0.23–0.87, P_trend = 0.02; CD8^high OR_{T3 vs T1} = 1.19, 95% CI 0.62–2.26, P_trend = 0.62; P_het = 0.04). n-6 PUFAs were suggestively inversely associated with CD8^high but not CD8^low cancers (CD8^high OR_{T3 vs T1} = 0.61, 95% CI 0.32–1.14, P_trend = 0.11; CD8^low OR_{T3 vs T1} = 1.63, 95% CI 0.87–3.04, P_trend = 0.12; P_het = 0.02). Trans fatty acids were positively associated with FAS^high but not FAS^low tumors (FAS^high OR_{T3 vs T1} = 2.94, 95% CI 1.46–5.91, P_trend = 0.002; FAS^low OR_{T3 vs T1} = 0.99, 95% CI 0.52–1.92, P_trend = 0.97; P_het = 0.01).

Conclusion

Results indicate that the effects of n-3 PUFAs, n-6 PUFAs, and trans fatty acids on breast cancer risk may vary by tumor tissue expression subtypes. Findings suggest potential immuno-modulatory and FAS-mediated mechanisms.