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Page 2 of 16 Yeger et al. J Cancer Metastasis Treat 2020;6:26 I http://dx.doi.org/10.20517/2394-4722.2020.61

INTRODUCTION
The association between diet and cancer incidence have generated great interest over many years when
evidence was obtained that specific regional plant based diets portended significantly lower numbers
[1]
of specific cancers despite confounding factors that should have predicted an incidence closer to
other regions. One such association receiving increased attention both for normal health and a lower
[2-4]
incidence of cancer is the association with the Mediterranean diet (MedDiet) . The MedDiet, also lower
in calories, saturated fats, and higher in fiber, also has strong benefits for reduction in cardiovascular
[3,5]
disease and generally, inflammatory conditions . A dissection of the diets in this region highlights the
intake of polyphenols and in particular the family of cruciferous vegetables (the Brassica cabbage related
family) consumed. The Brassica family contains high amounts of a family of precursors and derivatives
of isothiocyanates (ITCs). Populations in the region bordering the Mediterranean also consume large
[4]
amounts of extra virgin olive oil (EVOO) with a high content of unsaturated fatty acids . Interestingly,
although a high amount of oleic acid appears to promote cancer growth, the other components in EVOO
(hydroxytyrosol, oleuropein, pinoresinol, apigenin, squalene, and maslinic acid) counter the effects of
oleic acid and are indeed protective . Many other studies support the protective effect of olive oil on gut
[4]
[6,7]
and the development of colorectal cancer . Our older studies demonstrated that squalene protects bone
marrow progenitors against cancer cytotoxic cisplatin, and that apigenin (along with other flavonoids)
[8]
can significantly inhibit proliferation of neuroblastoma tumor cells . Recent studies indicate that the high
content of squalene epoxidase in cancers (in the cholesterol oxidation pathway that metabolizes cytotoxic
[9]
squalene) and is associated with worse overall survival . Thus, although squalene is cytotoxic, its anti-
inflammatory activity, and the complex of factors in olive oil together operate positively. Thus protection
against cancer rests on a complex of dietary factors in the context of human lifestyle habits and genetic
contributions.

In this review we present a broader window on the ITC based family of compounds, including our research
on sulforaphane (SFN), and make a case for the value of such phytochemicals in cancer prevention and
treatment, as well as for other important physiological benefits that together support why ITC based, and
in general phytochemical rich diets, working in concert with other healthful components like olive oil can
make a real difference to the overall health of people. The review will cover most of the key issues in this
class of ITC compounds and end with insights into potential therapeutic applications.

CANCER RISK
Cancer remains a major risk to health and longevity. Although, according to the National Cancer Institute
(USA) [10,11] the decrease in cancer associated deaths have been decreasing in an encouraging manner, the
statistics indicate that cancer still constitutes a significant burden (only second to cardiovascular disease) on
health and survival. For example, in 2018, approximately 1,735,350 new cases of cancer were estimated to
be diagnosed in the United States, and 609,640 people estimated to die from the disease. By 2020, 1,806,590
new cancer cases and 606,520 cancer deaths have been projected. Relative to older data the drop in death
rate is trend setting and reflects earlier detection and better treatments. The most common cancers (listed
in descending order according to estimated new cases in 2018) are breast cancer, lung and bronchus cancer,
prostate cancer, colon and rectum cancer, melanoma of the skin, bladder cancer, non-Hodgkin lymphoma,
kidney and renal pelvis cancer, endometrial cancer, leukemia, pancreatic cancer, thyroid cancer, and liver
cancer. From the data the number of new cases of cancer (cancer incidence) is 439.2 per 100,000 men and
women per year (based on 2011-2015 cases). The number of cancer deaths (cancer mortality) is 163.5 per
100,000 men and women per year (based on 2011-2015 deaths). Cancer mortality is higher among men
than women (196.8 per 100,000 men vs. 139.6 per 100,000 women, respectively). When comparing groups
based on race/ethnicity and sex, cancer mortality is highest in African American men (239.9 per 100,000)
and lowest in Asian/Pacific Islander women (88.3 per 100,000). Estimated national expenditures for cancer