Plasma fatty acids and risk of colon and rectal cancers in the Singapore Chinese Health Study

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; P trend = 0.005) and linoleic acid (OR = 0.43; 95% CI: 0.23, 0.82; P trend = 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; P trend = 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; P trend = 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.

Stool pattern is associated with prevalence of tumorigenic bacteria of the microbiota and plasma and fecal fatty acids in healthy Japanese adults

“…It has been reported that the distal colon transit, re ected in stool frequency, was associated with not only plasma acetate and fecal SCFAs [38], but also with microbiota diversity, especially the Firmicutes taxa (Faecalibacterium, Lactococcus, and Roseburia) [39]. Our results indicated that the stool pattern that showed a relationship with the prevalence of pks + E. coli was also signi cantly correlated with certain plasma fatty acids, including α-linoleic acid [40] and certain fecal SCFAs, such as propionate [34] and isovaleric acid [35]. These were also associated with higher incidences of CRC, supporting previous ndings.…”

Preferential uptake of polyunsaturated fatty acids by colorectal cancer cells

“…Fatty acids (FAs) are a heterogeneous group of lipids with different chain length, degree of saturation and metabolic effects 2 . A growing body of evidence shows that CRC is associated with alterations of FA profiles in serum and tumor tissues [3][4][5][6][7][8] . Recently, we demonstrated an increase in the levels of saturated and monounsaturated very long chain FAs in tumor tissues and sera of CRC patients 3 , co-existing with enhanced expression of FA elongases 1 and 6 in cancer tissues 3 .…”

“…There are some studies on the potential role of PUFAs in diagnosis of CRC. Some authors found that lower ALA and LA and higher ARA levels in plasma are associated with increased CRC risk 7,15,16 . Rifkin et al 17 found that increased risk of colorectal adenoma is associated with higher levels of ARA and lower levels of eicosapentaenoic acid (EPA, 20:5 n-3) in erythrocyte membrane phospholipids.…”

“…Also there are studies suggesting that some oxidized metabolites of PUFAs might be used as potential biomarkers of cancer 19,20 . Published results on PUFA alterations in CRC are inconclusive, as previous studies documented either an increase or a decrease in the levels of various PUFAs in serum/plasma or cancer tissues 5,7,9,[21][22][23][24] . To address those discrepancies, we determined PUFA levels in sera and CRC tissues from the same patients.…”

A prospective study of erythrocyte polyunsaturated fatty acids and risk of colorectal serrated polyps and conventional adenomas

“…PUFAs in relation to colorectal neoplasia, [17][18][19][20] but the results have been inconsistent. The composition of PUFAs in erythrocyte membrane represents an integrated measure of the interactions between dietary PUFAs, other dietary factors and PUFA metabolism.…”