Opposing associations of serum n‐3 and n‐6 polyunsaturated fatty acids with colorectal adenoma risk: An endoscopy‐based case–control study

Abstract

Several human and animal studies have shown that n-3 polyunsaturated fatty acids (PUFA) might be associated with a decreased risk, whereas other studies showed that n-6 PUFA may be associated with an increased risk of colorectal cancer. However, results from these studies are not consistent. We evaluated the associations between serum n-3 and n-6 PUFA levels and colorectal adenoma risk in an endoscopy-based case-control study, conducted in The Netherlands between 1997 and 2002. We included 363 cases of colorectal adenomas and 498 adenoma-free controls. Serum fatty acids were measured in cholesteryl esters. Logistic regression models were used to calculate odds ratios (OR), which were adjusted for age, gender and alcohol intake. Total serum n-3 PUFA levels were inversely associated with colorectal adenoma risk, the OR comparing the third tertile with the first tertile was 0.67 [95% confidence interval (CI) 0.46-0.96, p for trend 5 0.03]. Serum eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) and the n-3/n-6 ratio were inversely associated with colorectal adenoma risk, but these were not statistically significant. In contrast, the risk of colorectal adenomas was increased by total n-6 PUFA with an OR of 1.68 (95% CI, 1.17-2.42, p for trend 5 0.006) and by linoleic acid (LA; C18:2n-6) with an OR of 1.65 (95% CI, 1.15-2.38, p for trend 5 0.007). This is the first observational study that simultaneously finds an inverse association of serum n-3 PUFA and a positive association of n-6 PUFA with colorectal adenoma risk.

Fish fatty acids alter markers of apoptosis in colorectal adenoma and adenocarcinoma cell lines but fish consumption has no impact on apoptosis-induction ex vivo

“…Furthermore it is probable that an alteration of the membrane composition by n-3 PUFA enrichment might also influence downstream signalling pathways and so support apoptosis [26][27][28][29][30]. An increase of n-3 PUFAs in cell membranes has previously been demonstrated to occur in humans eating a high-fish diet [31,32] as well as in rats provided a fish-oil enriched feed [33] and in vitro by supplementing cell cultures with PUFAs [34]. Thus, it is already acknowledged that DHA and EPA in vitro are likely to exert apoptosis-inducing effects in human colon adenocarcinoma cells such as HT29 and Caco-2 [28,30,[35][36][37].…”

Erythrocyte Membrane Phospholipid Fatty Acid Concentrations and Risk of Colorectal Adenomas: A Case–Control Nested in the French E3N-EPIC Cohort Study

“…Two case-control studies reported an inverse (but nonsignificant) association between serum n-3 long-chain PUFA levels and colorectal adenoma risk (17,18). Two prospective studies based on food frequency questionnaires did not find any association between n-3 PUFA intakes and risk of colorectal adenomas (11,12), but association was not tested separately on advanced and nonadvanced colorectal adenoma risk.…”

“…However, few studies examined the association between biomarkers of fatty acids and colorectal adenomas. One study reported an inverse association between serum levels of n-3 PUFA and colorectal adenoma risk, whereas a positive association was found for n-6 PUFA (17). Another study found a positive association between serum levels of saturated and monounsaturated fatty acids and colorectal adenoma risk, whereas a negative association was found for some n-6 and n-3 PUFA (18).…”

Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells

“…EPA was found to inhibit colon crypt cell proliferation in vivo [13] . A recent study has demonstrated an inverse association of the n-6/n-3 ratio with colon adenoma formation [14] . In an animal model system with increased amounts of endogenously synthesized n-3 PUFA (the fat-1 mouse), two studies have shown a protective effect against colon tumor development [15,16] .…”