TY - JOUR
T1 - Erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers and fatty acid synthase
T2 - A nested case-control study
AU - McGee, Emma E.
AU - Kim, Claire H.
AU - Wang, Molin
AU - Spiegelman, Donna
AU - Stover, Daniel G.
AU - Heng, Yujing J.
AU - Collins, Laura C.
AU - Baker, Gabrielle M.
AU - Farvid, Maryam S.
AU - Schedin, Pepper
AU - Jindal, Sonali
AU - Tamimi, Rulla M.
AU - Eliassen, A. Heather
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/7/22
Y1 - 2020/7/22
N2 - 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 CD8low but not CD8high cancers (CD8low ORT3 vs T1 = 0.45, 95% CI 0.23-0.87, P trend = 0.02; CD8high ORT3 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 CD8high but not CD8low cancers (CD8high ORT3 vs T1 = 0.61, 95% CI 0.32-1.14, P trend = 0.11; CD8low ORT3 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 FAShigh but not FASlow tumors (FAShigh ORT3 vs T1 = 2.94, 95% CI 1.46-5.91, P trend = 0.002; FASlow ORT3 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.
AB - 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 CD8low but not CD8high cancers (CD8low ORT3 vs T1 = 0.45, 95% CI 0.23-0.87, P trend = 0.02; CD8high ORT3 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 CD8high but not CD8low cancers (CD8high ORT3 vs T1 = 0.61, 95% CI 0.32-1.14, P trend = 0.11; CD8low ORT3 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 FAShigh but not FASlow tumors (FAShigh ORT3 vs T1 = 2.94, 95% CI 1.46-5.91, P trend = 0.002; FASlow ORT3 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.
KW - Breast cancer
KW - COX-2
KW - Erythrocyte membrane
KW - Fatty acid
KW - Fatty acid synthase
KW - Immune marker
KW - Inflammation
KW - Tumor-infiltrating lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=85088434117&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088434117&partnerID=8YFLogxK
U2 - 10.1186/s13058-020-01316-4
DO - 10.1186/s13058-020-01316-4
M3 - Article
C2 - 32698885
AN - SCOPUS:85088434117
SN - 1465-5411
VL - 22
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 78
ER -