Nutritional factors play a major role in cancer initiation and development [76
]. The present systematic review and meta-analysis of observational studies revealed that, overall, olive oil consumption was associated with lower odds of cancer development. Most prominent results were observed for breast cancer and cancers of the digestive system, while the aforementioned relationship was similar to studies performed in Mediterranean as well as non-Mediterranean countries. Meta-analyses have several weaknesses, due to inherent biases and differences in study designs (different control for residual confounding, different socio-demographic and other lifestyle characteristics that may alter food habits), publication bias, etc [9
]. The use of only case-control studies may also limit the interpretation of the results as causal. Moreover, in 2 studies no exact information about the effect size was reported in the retrieved abstract; however, the direction of the effect was similar to the other studies. Therefore, it could be speculated that the inability to include these studies in the meta-analysis would not alter the combined results. At this point it should also be noticed that although it is acceptable to consider studying the risk associated with extreme categories, such as the highest vs. lowest, the use of an ordered variable, like the effect sizes per incremental quintile would be preferable; however, the available results did not allow for such an analysis. Moreover, the analysis of studies was focused only on those that evaluated raw olive oil intake, in order to avoid the synergistic effect of cooking. Nevertheless, the large number of studies enrolled, makes the present work one of the few that systematically evaluated the cancer- monousaturated lipid (especially olive oil) associations.
Ecologic comparisons and meta-analysis of prospective cohort studies suggest that cancer morbidity and mortality are lower in Mediterranean countries, where olive oil represents a substantial fraction of dietary fat [77
]. Prospective studies show evidence that higher degree of adherence to the Mediterranean diet is associated with a reduced mortality for cancer of all types, examined in one model[78
]. According to a review, in Western countries, approximately 25% of the incidence of colorectal cancer, 15% of breast cancer, and 10% of prostate, pancreas, and endometrial cancer could be prevented if traditional Mediterranean dietary patterns were followed [79
]. However, ecologic comparisons are characterized by complex forms of confounding, thus, are difficult to interpret [4
], in addition, though the protective role of Mediterranean diet has been advocated by several studies, mutual confounding among food groups and nutrients, as plant foods and olive oil, have not been addressed in depth, and, it is probable that available Mediterranean dietary scales cannot capture all the interrelations among a multitude of foods consumed traditionally.
From ecologic comparison of 28 countries, 76% of the inter-country variation in colorectal cancer incidence rates could be attributed to three dietary factors: meat, fish and olive oil, in combination; meat and fish were found positively associated, whereas olive oil was negatively associated. The authors stated that olive oil could influence secondary bile acid patterns in the colon that, in turn, might influence polyamine metabolism in colonic cells reducing possibility to progression from normal mucosa to adenoma and, eventually, carcinoma [80
]. Also, olive oil seems to be inversely associated with breast cancer risk, although there are no robust data to consider. Less experimental and epidemiologic evidence has been collected for the other types of cancer, such as gynecological, urological and respiratory cancers, and there are no available data for haemopoietic malignancies. As it is stated previously, most available studies till today are case-control ones and in the majority of them total energy intake is controlled for. Most of these studies are examining the role of a series of different nutrients and are not examining the specific role of added fats, monounsaturated fats (in Mediterranean countries) and in particular olive oil, to the above mentioned different types of cancer.
In addition, a recent meta-analysis of biomarkers of dietary fatty acid intake and risk of breast cancer concluded that there is no significant association between oleic acid and breast cancer risk in case-control studies, whereas in cohort studies there was significant higher risk for women with high levels of this fatty acid [81
]. These papers referred were not taken into consideration, because it was not clear from the studies that oleic acid was deriving from olive oil only or from other dietary sources as well. Also, selection and nutrient-specific information biases are reported to be minimized in some of the studies taken into consideration, while others have also provided additional results after taking into consideration the mutual confounding by different food groups and nutrients, such as of olive oil and vegetables. Finally, though there is not enough data for skin cancer, it could be stated that due to the high concentrations of squalene in olive oil, which is transferred to the skin, olive oil intake could be searched for a protective effect against skin cancer [5
Evidence to support that olive oil conveys protection against occurrence of different types of cancer necessitates more epidemiological studies, especially prospective ones, specifically designed to address these issues, which would all adjust for total energy intake. The ongoing and future well designed cohort studies will help to further examine the association and questions arising, such as, firstly if olive oil intake facilitates more vegetable intake, thus, maximising its beneficial effects to cancer prevention, and secondly, if the possible beneficial effects of olive oil are attributed to its monounsaturated content or to its other components, could be addressed [1
]. Large enough and well conducted trials, both for countries with high as with low intake of olive oil, could be necessary, for the purpose of generalisability.