Thursday, July 8, 2010

Olive oil and cancer

Could a diet where olive oil is the primary source of fat assist in delaying or preventing the onset of cancer? That's a tempting question and certainly a good one for nutrigenomics. As one might expect, the answer is both a yes and a no.

Yes. A recent study by Hirsch, Struhl, et al. used two isogenic cancer models to uncover the transcript profile and gene signature linking cancer with inflammatory and metabolic diseases. This group identified 345 genes whose expression signature is also involved in inflammation and metabolic diseases such as type 2 diabetes and cardiovascular disease. In fact, within these 345 genes are genes identified by GWAS (and other types of studies) for HDL-cholesterol (ABCA1 and GALNT2), obesity (NPC1), stroke (AIM1), and celiac disease (PTPN2, PTPRK, SCHIP1 and ZMIZ1), among others. Curiously, there is substantial sharing of genes between those upregulated in this cancer set and those that we identified as downregulated after acute intake of phenol-rich olive oil. Ten genes are shared. This is a 4.2-fold enrichment over what one would expect by chance given the size of the two gene sets. That sounds quite strong and the genes look mighty interesting:

ANXA3 - annexin A3
CXCL3 - chemokine (C-X-C motif) ligand 3
DUSP1 - dual specificity phosphatase 1
EREG - epiregulin
IER2 - immediate early response 2
IL1B - interleukin 1, beta
IL6 - interleukin 6 (interferon, beta 2)
JUNB - jun B proto-oncogene
SOCS3 - suppressor of cytokine signaling 3
SOD2 - superoxide dismutase 2, mitochondrial

These are some big players and so perhaps there is an olive oil-cancer prevention link.


No. Because not everyone living in countries with heavy use of olive oil in the diet, countries such as Spain and Italy, adheres to a typical or Mediterranean diet, population data on cancer rates are not really an accurate way to assess that an olive oil-rich or Mediterranean diet lowers one's risk of cancer. Besides, cancer is too general a term - risk of specific types of cancer should be measured. For example, adherence to the traditional Mediterranean diet is associated with reduced risk of upper aerodigestive tract cancers and reduced risk of colorectal cancer has been observed in those who follow a diet higher in fruits/vegetables, lower in fat and more toward a Mediterranean diet.

The list of common cancer pathway genes is much greater than 10. Some 240 genes are upregulated and 105 are downregulated. Thus, while the 10 cancer pathway, olive oil-sensitive genes listed above are a highly interesting list, this is by no means sufficient to unequivocally state that a diet high in phenol-rich olive oil will prevent cancer.

Furthermore, many of the genes in this list of 10 are common to several important pathways. IL1B is a pro-inflammatory mediator and is also involved in the postprandial response of triglyderides. The floxed Socs3 gene in mouse gives an animal that is resistant to diet-induced obesity and this gene has been assigned to an insulin resistance inflammation network. One major point of our olive oil paper was the anti-inflammation nature of the response to the phenol-rich olive oil on gene expression in PBMCs. A recent paper essentially confirms this finding. Hence, the dual assignment of many genes to a cancer pathway and something else like inflammation is highly intriguing, but caution is, as always, warranted in condensing the complexities of metabolism, inflammation and cancer to a single kernel of dietary advice.

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