Key Points
Colorectal cancer is the fourth most common cancer in the US. Fatty acids may contribute to colorectal carcinogenesis through a variety of mechanisms including the modulation of immunity, inflammation, and cell signaling. Until recently, only two nested case-control studies with relatively small sample size evaluated levels of fatty acids in pre-diagnostic blood samples in relation to colorectal cancer risk. Both studies reported statistically significant inverse associations with n-3 PUFAs, and no association with n-6 PUFAs, including arachidonic acid, or other long-chain fatty acids. In contrast, recent findings from a larger case-cohort study included a statistically significant positive association between plasma saturated fatty acids (SFAs) and colorectal cancer, and no association with n-3 PUFAs.
The findings of this study included statistically significant inverse associations with colon cancer risk for higher levels of the essential PUFAs α-linolenic and linoleic acids, the major contributing MUFA oleic acid, and SCD-1 index reflecting increased synthesis of oleic acid. The results also included a statistically significant positive association with colon cancer for the desaturase indices reflecting increased synthesis of arachidonic acid. This study found no associations with EPA or DHA and colorectal cancer risk. The findings support an alternative role of the essential n-3 PUFA α-linolenic acid against the development of colon cancer by reducing inflammation and inhibiting proliferation and invasion, rather than as a precursor to EPA or DHA. In addition, the finding support a potential preventive role for the essential n-6 PUFA linoleic acid in colon carcinogenesis that may be due in part to its effect on increasing apoptosis and decreasing cancer cell proliferation. In the present study, there not no associations found between fatty acids and rectal cancer risk. No previous study has evaluated the association between biomarkers of fatty acids and rectal cancer risk. In conclusion, the present study demonstrated an inverse association with essential PUFAs α-linolenic and linoleic acids, and the major contributing MUFA oleic acid, and its increased synthesis capacity with colon cancer risk. The present study also showed a positive association with high plasma levels of arachidonic acid and its increased synthesis capacity on colon cancer risk. These novel findings, if confirmed, have implications for colon cancer prevention.
ABSTRACT
Fatty acid composition in plasma captures both dietary intake and endogenous synthesis. Prospective analyses of plasma fatty acid composition are needed to establish the role of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) on risk of developing colorectal cancer. To evaluate associations between plasma fatty acid composition and colon or rectal cancer risk separately, a nested case-control study of 350 colorectal (211 colon and 139 rectal) cancer cases and an equal number of individually matched control subjects was conducted within the Singapore Chinese Health Study, a cohort of 63,257 men and women recruited between 1993 and 1998. Fatty acids in pre-diagnostic plasma were quantified using gas chromatography-tandem mass spectrometry. Conditional odds ratios (ORs) and 95% confidence intervals (CIs) comparing highest to lowest quartiles are presented. For colon cancer, inverse associations were reported with higher essential PUFAs, α-linolenic acid (OR = 0.41; 95% CI: 0.23, 0.73; Ptrend = 0.005) and linoleic acid (OR = 0.43; 95% CI: 0.23, 0.82; Ptrend = 0.008). Higher desaturase activity in the n-6 PUFA synthesis pathway estimated by the arachidonic:linoleic acid ratio was associated with increased colon cancer risk (OR = 3.53; 95% CI: 1.82, 6.85; Ptrend = 0.006), whereas higher desaturase activity in the MUFA synthesis pathway estimated by the oleic:stearic acid ratio was associated with decreased colon cancer risk (OR = 0.42; 95% CI: 0.19, 0.92; Ptrend = 0.024). There was no significant association between the essential fatty acids or the desaturase indices and rectal cancer risk. Endogenous synthesis of arachidonic and oleic acids has an impact on colon cancer development.
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