Our nested case-control study among postmenopausal smokers did not provide evidence for associations with breast cancer risk for total of saturated, monounsaturated, n-3, n-6, or trans fatty acids. By individual fatty acids, we unexpectedly observed an inverse association with the trans linoleic acid isomer, 18:2n6tt. In stratified analyses by smoking status, long-chain SFAs (22:0 and 24:0) and total 16:1 trans fatty acids were positively associated with breast cancer risk among current smokers, whereas none of the fatty acids was associated among former smokers.
Previous epidemiologic studies on the association between total trans
fatty acids and the risk of breast cancer yielded mixed results. Two observational studies reported a positive association (13
). In contrast, a favorable breast cancer prognosis was associated with a higher trans
fatty acids in adipose tissue (15
). Consistent with our finding, four observational studies reported no association (16
). Furthermore, separate analysis by major isomers of trans
fatty acids unexpectedly showed an inverse association with one trans
linoleic acid isomer (18:2n6tt), while the other two isomers (18:2n6ct and 18:2n6tc) were not associated or, if any, possibly positively for 18:2n6tc. This finding does not corroborate with a recent case-control study that reported no association with 18:2n6tt isomer (19
), nor with putative negative effects of trans
fatty acids derived from partially hydrogenated vegetable oils on cancer (3
). Partially hydrogenated vegetable oils are considered as the major dietary source of the trans
linoleic acid. To explore if specific foods contribute to 18:2n6tc compared with the other trans
fatty acids, we calculated correlations for all individual and combined trans
fatty acids isomers with several foods and food groups. However, we did not observe any moderate or strong correlations for any trans
fatty acids isomer; the strongest correlation was 0.18 for margarine and total trans
18:1 fatty acids. Accordingly, and given that the 18:2n6tt isomer contributes only 0.03% to the total fatty acid composition, this unexpected inverse association might be a chance finding.
Our finding of no association between the activity of stearoyl-CoA desaturase, indicated by SI n-9, and breast cancer risk is consistent with several studies (20
) while two studies reported an inverse association (24
). Since it was postulated that factors other than fatty acids (e.g., insulin sensitivity and estrogen levels) may affect the stearoyl-CoA desaturase activity (24
), the observed association may have been modified by these factors. However, due to lack of measurement on these factors, we were unable to further investigate this potential interaction.
The underlying biological mechanism for a potential interaction of long-chain SFAs (22:0 and 24:0) and 16:1 trans
fatty acids with smoking status is unknown. However, we previously showed that a moderate-fat diet (34% of energy from fat) resulted in higher fractions of 22:0 and 24:0 fatty acids as well as 16:1 trans
fatty acids in plasma phospholipids than a low-fat diet (17% of energy from fat) in an 6-week intervention study (9
). Hence, it is interesting to speculate if dietary habits of former smokers (e.g., by lowering fat intake) could have changed when they stopped smoking. These findings need to be replicated.
Strengths of our study include our prospective design with up to 14 years of follow-up and the use of an objective measure for the fatty acid composition. Furthermore, this is the first study among cigarette smokers that examined the effect of current and past smoking on the association between fatty acid composition and breast cancer risk. Conversely, the generalizability of our findings to a healthy population may be limited. This is also one of the very few studies that examined the effect of the different trans fatty acid isomers on breast cancer risk.
A limitation of our study is the small sample size with limited power, especially for subgroup analysis. Another potential limitation is our inability to adjust for some of the established risk factors for breast cancer (i.e., age at menarche and hormone regimen) in the analyses due to lack of information. Two early studies using biomarker of fatty acids (13
) reported comparable risk estimates with and without adjustment for breast cancer risk factors. Thus, this limitation is probably less likely to affect our risk estimates.
Overall, we observed no significant association between fatty acids in serum phospholipids and breast cancer risk, except for the trans linoleic acid, 18:2n6tt. Our finding of a positive association with long-chain SFAs (22:0 and 24:0) and total 16:1 trans fatty acids only in current smokers is intriguing and may suggest an effect modification by smoking status. Our findings need to be confirmed in larger epidemiologic studies in order to further elucidate the effect of specific fatty acids, particularly isomers of trans fatty acids, on the risk of breast cancer.