N‐3 and N‐6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case‐control study in Tours, France

Abstract

Experimental studies have indicated that n-3 fatty acids, including alpha-linolenic acid (18:3 n-3) and long-chain n-3 polyunsaturated fatty acids inhibit mammary tumor growth and metastasis. Earlier epidemiological studies have given inconclusive results about a potential protective effect of dietary n-3 polyunsaturated fatty acids on breast cancer risk, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis that n-3 fatty acids protect against breast cancer, we examined the fatty acid composition in adipose tissue from 241 patients with invasive, nonmetastatic breast carcinoma and from 88 patients with benign breast disease, in a case-control study in Tours, central France. Fatty acid composition in breast adipose tissue was used as a qualitative biomarker of past dietary intake of fatty acids. Biopsies of adipose tissue were obtained at the time of surgery. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Unconditional logistic regression modeling was used to obtain odds ratio estimates while adjusting for age, height, menopausal status and body mass index. We found inverse associations between breast cancer-risk and n-3 fatty acid levels in breast adipose tissue. Women in the highest tertile of alpha-linolenic acid (18:3 n-3) had an odds ratio of 0.39 (95% confidence intervals [CI] ‫؍‬ 0.19 -0.78) compared to women in the lowest tertile (trend p ‫؍‬ 0.01). In a similar way, women in the highest tertile of docosahexaenoic acid (22:6 n-3) had an odds ratio of 0.31 (95% CI ‫؍‬ 0.13-0.75) compared to women in the lowest tertile (trend p ‫؍‬ 0.016). Women in the highest tertile of the long-chain n-3/total n-6 ratio had an odds ratio of 0.33 (95% confidence interval ‫؍‬ 0.17-0.66) compared to women in the lowest tertile (trend p ‫؍‬ 0.0002). In conclusion, our data based on fatty acids levels in breast adipose tissue suggest a protective effect of n-3 fatty acids on breast cancer risk and support the hypothesis that the balance between n-3 and n-6 fatty acids plays a role in breast cancer.

Omega-3 and Omega-6 Fatty Acids in Blood and Breast Tissue of High-Risk Women and Association with Atypical Cytomorphology

“…Our results are consistent with studies that find lower longchain omega-3 fatty acids and omega-3:6 ratios in RBCs (20,21) and adipose tissue (40,41) from women with breast cancer compared with controls. Omega-3 fatty acids are especially prone to oxidation (42), and it is possible that the lack of correlation between omega-3 fatty acids in blood and tissue and breast cancer risk in nested, case-control studies (22)(23)(24)(25)(26)(27)(28) is due to the complications of analyzing the fatty acid composition in samples stored for periods ranging from 4 to 25 years (23,25).…”

Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study

“…Results of these latter studies are mixed. Some (Zhu et al, 1995;Maillard et al, 2002) but not all (London et al, 1993;Petrek et al, 1994;Simonsen et al, 1998) studies found a protective effect. Six cohort studies, in Norway (Vatten et al, 1990), Japan (Key et al, 1999), and in the US (Stampfer et al, 1987;Toniolo et al, 1994;Gertig et al, 1999;Holmes et al, 1999), have investigated fish or marine n-3 fatty acid intake.…”

“…Relatively sparse data are available on the potentially opposing and interactive effects of n-3 and n-6 fatty acids on breast cancer in humans (Simonsen et al, 1998;Maillard et al, 2002;Goodstine et al, 2003). Here, we report on the effects of different types of fatty acids (saturated, monounsaturated, polyunsaturated) and certain individual fatty acids (n-3, n-6) on breast cancer development in the Singapore Chinese Health Study, an ongoing prospective cohort study with a focus on diet and cancer risk.…”

Melanoma growth is reduced in fat-1 transgenic mice: Impact of omega-6/omega-3 essential fatty acids

“…Because eicosanoid precursors (i.e., AA and EPA) compete for the same metabolic enzymes [cyclooxygenase (COX) and lipoxygenase], the availability of AA and EPA and their ratio in cellular lipids determine the cell eicosanoid profile. Thus, it has been suggested that a balanced n-6͞n-3 ratio of body lipids is essential for normal growth and development and plays an important role in prevention as well as treatment of many clinical problems, including cancer (10)(11)(12)(13).…”

“…Emerging evidence suggests that the n-6͞n-3 fatty acid ratio, rather than the absolute levels of the two classes of PUFAs, is the principal factor in the antitumor effects of n-3 PUFAs (10)(11)(12). Experimental data show that the efficacy of n-3 PUFAs in suppressing cancer growth depends not only on the amount of n-3 PUFAs but also on background levels of n-6 PUFAs (14).…”