The present case-control study was designed to examine the associations of the 5-lipoxygenase gene (ALOX5) and 5-lipoxygenase-activating protein gene (ALOX5AP) with breast cancer risk among Latina, African-American, and white women from the San Francisco Bay area. The omega-6 polyunsaturated fatty acid 5-lipoxygenase pathway has been demonstrated to play a role in the development of breast cancer. The study included 802 breast cancer cases and 888 controls. Three ALOX5 polymorphisms (Sp1-binding site (-GGGCGG-) variable number of tandem repeat polymorphism, −1279 G>T (rs6593482), and 760 G>A (rs2228065)) and three ALOX5AP polymorphisms (poly(A) microsatellite, −4900 A>G (rs4076128), and −3472 A>G (rs4073259)) and were genotyped in the study participants. No significant main effects of ALOX5 and ALOX5AP genotypes on breast cancer risk were found that were consistent across race or ethnicity. However, a significant interaction between the ALOX5AP −4900 A>G polymorphism and dietary linoleic acid intake was observed (P = 0.03). In particular, among women consuming a diet high in linoleic acid (top quartile of intake, or greater than 17.4 g/day), carrying the AA genotype was associated with a higher risk of breast cancer (age- and race-adjusted odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.2-2.9) compared with those carrying genotypes AG or GG. Among women consuming less than or equal to 17.4 g/day of linoleic acid, ALOX5AP −4900 genotype was not found to be associated with breast cancer risk (adjusted OR = 0.9, 95% CI = 0.7-1.2). The authors conclude that the results support a role for n-6 polyunsaturated fatty acids in breast carcinogenesis and suggest that epidemiologic studies on dietary fat and breast cancer should take into account genetic predisposition related to n-6 polyunsaturated fatty acid metabolism.

The present French prospective study was designed to examine the associations between dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) and the risk of breast cancer. Experimental studies suggest that ω-6 PUFAs have detrimental effects and ω-3 PUFAs have beneficial effects on mammary carcinogenesis, perhaps in interaction with antioxidants. The study included 56,007 French women who completed a diet history questionnaire from which PUFA intakes were estimated. During a follow-up period of eight years, 1,650 of the women developed invasive breast cancer. Breast cancer risk was not found to be specifically associated with any dietary PUFA. However, some associations were observed by food source, suggesting other potential effects than PUFA intake per se. Breast cancer risk was found to be inversely associated with alpha-linolenic acid (ALA) intake from fruit and vegetables (highest vs. lowest quintile, hazard ratio (HR) = 0.74; 95% confidence interval (CI) 0.63 - 0.88; p for trend < 0.0001), and from vegetable oils (HR = 0.83; 95% CI 0.71 - 0.97; p trend 0.017). On the other hand, risk of breast cancer was positively associated with ALA intake from nut mixes (p trend 0.004), ALA intake from processed foods (p trend 0.068), and total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between ω-6 and long-chain ω-3 PUFAs: risk of breast cancer was found to be inversely related to long-chain ω-3 PUFAs in women belonging to the highest quintile of ω-6 PUFAs (p interaction 0.042). The authors comment that these results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and risk of breast cancer.

This San Francisco Bay area study examined the association between fat intake and use of fat in cooking and the risk of breast cancer in a population-based, multiethnic, case-control study. A food frequency questionnaire was used among 2,045 controls and 1,703 breast cancer cases diagnosed between 1995 and 1999. Preferred use of fat for cooking was also determined. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). High fat intake was found to be associated with increased risk of breast cancer (highest vs. lowest quartile, adjusted OR = 1.35, 95% CI = 1.10-1.65). A positive association was found for oleic acid (OR = 1.55, 95% CI = 1.14-2.10, P(trend) < 0.01) but not for linoleic acid or saturated fat. Increased risk was found for women cooking with hydrogenated fats (OR = 1.58, 95% CI = 1.20-2.10) or vegetable/corn oil (rich in linoleic acid; OR = 1.30, 95% CI = 1.06-1.58) compared to women using olive/canola oil (rich in oleic acid). The authors conclude that a low-fat diet may play a role in breast cancer prevention. They further speculate that monounsaturated trans fats may have driven the discrepant associations between types of fat and breast cancer.

The current prospective study was designed to investigate the effects of individual fatty acids on breast cancer risk. The study included 35,298 Singapore Chinese women 45 to 74 years of age in the Singapore Chinese Health Study, who were enrolled during the period April 1993 to year-end 1998. Upon recruitment, each woman was administered a face-to-face validated food frequency questionnaire including 165 food and beverage items. As of year-end 2000, 314 new cases of breast cancer had been diagnosed. Cox regression methods were used to calculated the association between individual fatty acids and the risk of breast cancer, while adjusting for age at baseline, year of interview, dialect group, level of education, daily alcohol intake, number of live births, initial age when menstrual periods became regular, and family history of breast cancer. Intake of saturated, monounsaturated and polyunsaturated fat overall were found to be unrelated to breast cancer risk. However, high dietary levels of omega-3 fatty acids from fish or shellfish (i.e., marine omega-3 fatty acids) were found to be significantly associated with reduced risk of breast cancer. Relative to the lowest fourth of intake, women in the higher three quartiles showed a 26% reduction in risk (relative risk (RR)=0.74, 95% confidence interval (CI)=0.58 - 0.94)). RRs were similar for the top three quartiles of omega-3 fatty acid intake (0.75, 0.75, 0.72, respectively). Overall, no association was found between omega-6 fatty acids and risk of breast cancer. However, among women in the lowest quartile of marine omega-3 fatty acids, a statistically significant increase in risk was observed in individuals belonging to the highest versus the lowest quartile of omega-6 fatty acid intake (RR=1.87, 95% CI=1.06-3.27); the corresponding RR for advanced breast cancer was 2.45 (95% CI=1.20-4.97, P for trend=0.01).

The current case-control study investigated the association between intake of omega-3 and other fatty acids and the omega-3/omega-6 polyunsaturated fatty acid ratio and breast cancer risk. Combining the data from two related Connecticut case-control studies resulted in a study group consisting of 1119 women (565 cases and 554 controls). A food-frequency questionnaire was used to gather information on dietary intake. No significant trends for any macronutrient or fatty acid were observed in the overall study population when comparing the highest to the lowest quartile of intake. However, for the premenopausal women considered alone, consumption of the highest compared with the lowest quartile of the omega-3/omega-6 ratio was associated with a nonsignificant lower risk of breast cancer [odds ratio = 0.59, 95% confidence interval 0.29-1.19, P for trend = 0.09]. The authors conclude that these results are consistent with the hypothesis that a higher omega-3/omega-6 ratio may reduce the risk of breast cancer, especially in premenopausal women.

The present case-control study was designed to investigate the relationship between the polyunsaturated fatty acid (PUFA) composition of breast adipose tissue and the risk of breast cancer. Animal studies suggest that dietary omega-6 (n-6) PUFAs, found in corn and safflower oils, may be precursors of compounds involved in the development of mammary tumors, whereas long-chain omega-3 (n-3) PUFAs, found in fish oil, can inhibit these carcinogenic effects. In the study, fatty acid levels in breast adipose tissue were used as a biomarker of past dietary intake of fatty acids. The hypothesis that breast cancer risk is negatively associated with the long-chain n-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid and positively associated with the n-6 PUFAs linoleic acid and arachidonic acid was tested. The study included 73 breast cancer patients and 74 controls with macromastia from whom breast adipose tissue was obtained. Fatty acid levels in the breast tissue were assessed using gas-liquid chromatography. Odds ratio estimates were obtained using a logistic regression model while adjusting for age. The age-adjusted n-6 PUFA content was found to be was significantly higher in breast cancer cases than in controls (P = 0.02). A trend was observed in the age-adjusted data suggesting that, at a given level of n-6 PUFA, long-chain n-3 PUFAs may have a protective effect against breast cancer (P = 0.06). A similar inverse relationship was found for long-chain n-3 to n-6 ratio when the data were adjusted for age (P = 0.09). The authors conclude that total n-6 PUFAs may be contributing to the high risk of breast cancer in the United States and that long-chain n-3 PUFAs, derived from fish oils, may have a protective effect.

The present study investigated the effects of diets supplemented with perilla, soybean and safflower oils on carcinogen-induced mammary gland and colon cancers in female Sprague-Dawley rats. Perilla oil contains a large fraction of omega-3 (n-3) alpha-linolenic acid, whereas soybean and safflower oil are rich in omega-6 (n-6) linoleic acid. Five-week-old rats were divided into groups of 23 or 24 and were first given three subcutaneous injections of 40 mg/kg body weight 1,2-dimethylhydrazine (DMH), followed by a single intragastric administration of 50 mg/kg body weight 7,12-dimethylbenz[a]anthracene (DMBA) within two weeks. Starting one week after the DMBA treatment and for the following 33 weeks, the animals were administered a pellet diet containing 10% perilla oil, soybean oil or safflower oil. It was found that the number of mammary tumors per rat was significantly lower in rats on the perilla oil diet (4.4 +/- 2.5) than on the soybean oil diet (6.5 +/- 3.9). Similarly, the colon tumor incidence was significantly lower in rats on the perilla oil diet (18.2%) than those on the safflower oil diet (47.4%). The number of colon tumors per rat was also lowest in rats receiving perilla oil. In addition, the incidence of nephroblastomas in rats on the perilla oil diet (0%) was significantly lower than that for the soybean oil diet (23.8%). The authors conclude that alpha-linolenic acid (n-3)-rich perilla oil inhibits development of mammary gland, colon and kidney tumors in rats compared to linoleic acid (n-6)-rich safflower or soybean oils.