Abstract 1869: Plasma fatty acids and colorectal cancer risk: The Singapore Chinese Health Study

Abstract

Abstract BACKGROUND: Fatty acids are a heterogeneous group of compounds that may promote or inhibit colorectal carcinogenesis. Fatty acid composition of plasma lipids capture dietary fat intake, as well as endogenous synthesis. Prospective analyses of fatty acid composition are needed to establish the role of long-chain monounsaturated and polyunsaturated fatty acids (PUFAs) on risk of developing colon cancer. METHODS:A nested case-control study of colon cancer (211 cases and 211 matched controls) was conducted within the Singapore Chinese Health Study, a cohort of 63,257 men and women ages 45 to 74 years who were recruited between 1993 and 1998. Fatty acids were quantified by gas chromatography-tandem mass spectrometry (GC-MS/MS) in plasma specimens that were collected an average of three years prior to colon cancer diagnosis. Desaturase activity was estimated as the product-to-precursor ratio of individual plasma fatty acids as follows: Δ5 desaturase = arachidonic (20:4n-6) to dihomo-γ-linolenic (20:3n-6) ratio, Δ6 desaturase = arachidonic (20:4n-6) to linoleic (18:2n-6) ratio, and stearoyl-coenzyme A desaturase (SCD-1) = oleic (18:1) to stearic (18:0) ratio. Conditional logistic regression was used to calculate multivariable odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:Statistically significant inverse associations with colon cancer risk were observed for the essential PUFAs, α-linolenic (18:3n-3) (OR = 0.42; 95% CI: 0.24, 0.75) and linoleic (18:2n-6) (OR = 0.44; 95% CI: 0.23, 0.82), comparing highest to lowest quartile. There were no associations with the longer-chain n-3 PUFAs, eicosapentanoic (20:5n-3) and docosahexaenoic (22:6n-3). A positive association was observed with arachidonic acid (20:4n-6) and with elevated synthesis of arachidonic acid, as quantified by the Δ5 and Δ6 desaturase indices. Compared with the 1st quartile, the OR (95% CI) for the 4th quartile was 2.31 (1.30, 4.12) and 3.38 (1.76, 6.49) for Δ5 and Δ6 desaturase indices, respectively (both Ps for trend <0.03). Higher levels and elevated synthesis of oleic acid (18:1), as estimated by SCD-1 index were associated with statistically significant lower colon cancer risk. Compared with the lowest SCD-1 quartile, the OR was 0.43 (95% CI: 0.20, 0.92) for the highest quartile (P for trend = 0.024). CONCLUSION: These novel data suggest that endogenous synthesis of arachidonic and oleic acid may play a critical role in the risk of developing colon cancer in humans. Once confirmed, chemopreventive strategies may be developed as modulators of desaturase activity that result in lower arachidonic acid and higher oleic acid synthesis. GRANTS: UM1 CA182876 and R01 CA144034. Citation Format: Lesley M. Butler, Woon P. Koh, Jin Su, Renwei Wang, Choon N. Ong, Jian M. Yuan. Plasma fatty acids and colorectal cancer risk: The Singapore Chinese Health Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1869. doi:10.1158/1538-7445.AM2015-1869