Dietary fats, fat metabolizing genes, and the risk of breast cancer

Animal studies have implicated dietary fats and fatty acid metabolites in mammary carcinogenesis. However, epidemiologic studies have failed to demonstrate a convincing link, probably due to methodological issues related to dietary assessment. An alternative approach to determine the existence of a relationship between fat intake and breast cancer is to examine whether the genetic polymorphisms in fat metabolic pathways are associated with breast cancer risk.;In a population-based multiethnic case-control study conducted in the San Francisco Bay area, we analyzed the association between dietary fat intake, n-6 polyunsaturated fat lipoxygenase gene polymorphisms, and breast cancer risk. Analysis of dietary fat intake among 1677 cases and 2010 controls found that high-fat intake was associated with increased risk of breast cancer (highest vs. lowest quartile, adjusted OR = 1.40, 95% CI: 1.14--1.72). Among types of fat, oleic acid (monounsaturated fat) was most strongly and consistently associated with increased risk (highest vs. lowest quartile, adjusted OR = 1.49, 95% CI: 1.21--1.84). Linoleic acid (n-6 polyunsaturated fat) was weakly associated with increased risk (highest vs. lowest quartile, adjusted OR = 1.17, 95% CI: 0.96--1.43). Polyunsaturated fat was more strongly associated with breast cancer risk when analyzing cooking fat usage among 832 cases and 1081 controls. A higher risk of breast cancer was found for women using vegetable/corn oil (rich for n-6 polyunsaturated fat) (adjusted OR = 1.34, 95% CI: 1.07--1.69), compared to women using olive or canola oil (rich for monounsaturated fat). Analysis of lipoxygenase gene polymorphisms among 805 cases and 889 controls found that the 5-lipoxygenase gene Sp1 binding site non-wild-type alleles were associated with increased risk of breast cancer among Latinas and African-Americans. The platelet-type 12-lipoxygenase gene polymorphisms, Arg261Gln and Asn322Ser, were also found to be associated with breast cancer risk among African-Americans. While the measurement error was still a concern in the analysis of fat intake in this study, our finding of an association between lipoxygenase gene polymorphisms and breast cancer risk implicates that dietary n-6 fats, metabolized through lipoxygenase pathways, may have a significant role in breast cancer.