Serum Phospholipids Fatty Acids and Breast Cancer Risk by Pathological Subtype

Abstract

This study evaluates whether serum phospholipids fatty acids (PL-FAs) and markers of their endogenous metabolism are associated with breast cancer (BC) subtypes. EpiGEICAM is a Spanish multicenter matched case-control study. A lifestyle and food frequency questionnaire was completed by 1017 BC cases and healthy women pairs. Serum PL-FA percentages were measured by gas chromatography-mass spectrometry. Conditional and multinomial logistic regression models were used to quantify the association of PL-FA tertiles with BC risk, overall and by pathological subtype (luminal, HER2+ and triple negative). Stratified analyses by body mass index and menopausal status were also performed. Serum PL-FAs were measured in 795 (78%) pairs. Women with high serum levels of stearic acid (odds ratio (OR)_T3vsT1 = 0.44; 95% confidence interval (CI) = 0.30-0.66), linoleic acid (OR_T3vsT1 = 0.66; 95% CI = 0.49-0.90) and arachidonic to dihomo-γ-linolenic acid ratio (OR _T3vsT1 = 0.64; 95% CI = 0.48-0.84) presented lower BC risk. Participants with high concentrations of palmitoleic acid (OR_T3vsT1 = 1.65; 95% CI = 1.20-2.26), trans-ruminant palmitelaidic acid (OR_T3vsT1 = 1.51; 95% CI = 1.12-2.02), trans-industrial elaidic acid (OR_T3vsT1 = 1.52; 95% CI = 1.14-2.03), and high oleic to stearic acid ratio (OR_T3vsT1 = 2.04; 95% CI = 1.45-2.87) showed higher risk. These associations were similar in all BC pathological subtypes. Our results emphasize the importance of analyzing fatty acids individually, as well as the desaturase activity indices.

Keywords: EpiGEICAM; breast cancer subtypes; breast neoplasm; desaturation indices; fats.

Figure 1

Breast cancer risk as a smooth function of serum phospholipid fatty acids. Curves represent adjusted odds ratios (solid lines) and 95% confidence intervals (dashed lines) based on restricted quadratic splines for (A) saturated fatty acids, (B) cis-monounsaturated fatty acids, (C) ruminant trans−fatty acids, (D) industrial trans−fatty acids, (E) n-6 polyunsaturated fatty acids and (F) n-3 polyunsaturated fatty acids, with knots at their 5th, 50th and 95th percentiles. The reference value for each group of fatty acids was set at the median of the first tertile (56.4%, 10.9%, 1.3%, 0.1%, 26.6% and 2.4% respectively). Odds ratios were obtained from conditional logistic regression models adjusted for educational level, body mass index one year prior to the interview, menopausal status, age at menarche, age at first birth, hormone replacement therapy use, alcohol consumption, self-assessed physical activity during the previous year, history of benign breast disease, family history of breast cancer and caloric intake. Bars represent the histogram of each group of fatty acids.