Ovarian cancer is the eighth most common cancer affecting women in Australia and the eighth-most common cause of death from cancer in women in the world.^1,2 In 2015, 1365 new cases of ovarian cancer were diagnosed in Australian women, with 938 deaths caused by ovarian cancer in 2016.²  The aetiology of ovarian cancer is multifactorial, encompassing reproductive, hormonal, genetic, environmental, and lifestyle factors. Among dietary risk factors, antioxidant compounds have been of interest.³

An imbalance between free radicals and antioxidants results in oxidative stress, which plays a role in cancer pathogenesis by causing structural alterations in DNA directly or indirectly through the formation of genotoxic lipid peroxidation by-products that react with DNA. In ovarian cancer, more than 90 % of cancers originate from the surface epithelial cells.  Given that ovarian surface cells are exposed to inflammatory agents and reactive oxygen species (ROS) generated during pre-ovulatory processes, it has been suggested that limiting oxidative stress to the ovarian epithelium could be considered a first-line defence against ovarian cancer.⁴

Selenium is an essential trace element, and its low status in humans has been linked to increased risk of various diseases, including cancer. Evidence from human epidemiological studies has increasingly indicated an inverse relationship between selenium status and cancer risk in human populations although, regarding ovarian cancer specifically, results to date have been mixed.⁵

Cellular processes and molecular pathways that may be involved in the anti-cancer effect of selenium include:⁶

• Seleno-enzymes involving the reduction of DNA damage, oxidative stress and inflammation;
• Induction of phase II conjugating enzymes involving detoxifying carcinogens and reducing DNA adduct formation;
• Enhancement of immune response including cytotoxic lymphocyte and natural killer cell activity;
• Increase in tumour-suppressor protein p53, which inhibits proliferation, stimulates DNA repair and promoting apoptotic death by acting as a transcription factor for several genes;
• Inactivation of protein kinase C, a signalling receptor that plays a crucial role in tumour promotion by oxidants;
• Alteration in DNA methylation, as abnormal methylation patterns are associated with neoplasia and inactivation of tumour-suppressor genes;
• Perturbation of the cell cycle, resulting in growth inhibition and may allow DNA repair to take place;
• Induction of apoptosis of cancer cells, which generally involves the sequential activation of the caspases;
• Inhibition of angiogenesis required for the growth and metastasis of tumours.

A recent population-based, case-control study sought to evaluate the associations of antioxidant intake with the risk of ovarian cancer in African-American women, who are known to have high mortality from the disease (n=406 ovarian cancer cases and n=632 age- and site-matched controls; aged 20 to 79 years).³ Exposure levels of antioxidant nutrients from both food sources and dietary supplements (specifically vitamins E and C, carotenoids, and selenium) were assessed.

Analysis of the data showed that women who reported the highest intakes of supplemental selenium (>20 mcg/day) had a 30% lower risk of ovarian cancer than those with no supplemental intake (p = 0.035). Similar associations were observed for both dietary and supplemental selenium, although statistical significance was reached only for supplemental intake. This inverse association was stronger in current smokers (p = 0.001). The associations with carotenoid intakes were weak and nonsignificant (p = 0.07–0.60). There was no association with dietary or supplemental intake of vitamin C, vitamin E, zinc or copper with ovarian cancer.

An earlier study examined selenium supplementation (200 mcg/day) as a supportive element in the treatment of ovarian cancer in women receiving chemotherapy (n=31).⁷ After 2 and 3 months, the patients receiving selenium supplementation showed a significant increase in the activity of glutathione peroxidase (p < 0.0015 and p < 0.0038, respectively) and of malondialdehyde (p<0.0363; p < 0.0489). Selenium administration for 3 months resulted in a significant increase of white blood cells (p < 0.0001). After 2 and 3 months, selenium supplementation also resulted in a significant decrease in hair loss (p < 0.0000; p < 0.0392), flatulence (p < 0.0000; p < 0.0000), abdominal pain (p < 0.0006; p < 0.0202), weakness (p < 0.0001; p < 0.0000), malaise (p < 0.0017; p < 0.0000), and loss of appetite (p < 0.0000; p < 0.0000).

These findings highlight the need for practitioners to consider the beneficial role of selenium in supporting patients at risk of, or who have a current diagnosis of ovarian cancer, particularly in those patients with suboptimal dietary intake. Practitioners should consider the following treatment approaches:

• Recommend that patients supplement with an organic form of selenium at a dose of between 20 – 200 mcg/day. There is good evidence that supplementation with organic forms of selenium, such as selenomethionine, can maintain an increased selenium status for a longer period after its discontinuation compared to inorganic forms such as selenate. Organic forms have also been shown to maintain the activities of selenoenzymes during periods of selenium depletion for longer than those containing inorganic selenium.^8,9
• Educate patients of the importance of consuming a diet rich in high-fibre and anti-inflammatory foods such as oily fish, fruits, vegetables, nuts and seeds, and to limit pro-inflammatory foods such as sugary drinks, refined carbohydrates, trans fats and processed meats.

References

1. World Ovarian Cancer Coalition. The World Ovarian Cancer Coalitition Atlas: Global trends in incidence, mortality and survival, 2018.
2. Cancer Council. Ovarian Cancer. 13/11/2019.
3. Terry, P.D., et al., Supplemental Selenium May Decrease Ovarian Cancer Risk in African-American Women. J Nutr, 2017. 147(4): p. 621-627.
4. Murdoch, W.J. and J.F. Martinchick, Oxidative damage to DNA of ovarian surface epithelial cells affected by ovulation: carcinogenic implication and chemoprevention. Exp Biol Med (Maywood), 2004. 229(6): p. 546-52.
5. Tinggi, U., Selenium: its role as antioxidant in human health. Environmental health and preventive medicine, 2008. 13(2): p. 102-108.
6. Rayman, M.P., Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc Nutr Soc, 2005. 64(4): p. 527-42.
7. Sieja, K. and M. Talerczyk, Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy. Gynecol Oncol, 2004. 93(2): p. 320-7.
8. Thomson, C.D., et al., Long-term supplementation with selenate and selenomethionine: selenium and glutathione peroxidase (EC 1.11.1.9) in blood components of New Zealand women. Br J Nutr, 1993. 69(2): p. 577-88.
9. Evans, S.O., P.F. Khairuddin, and M.B. Jameson, Optimising Selenium for Modulation of Cancer Treatments. Anticancer Res, 2017. 37(12): p. 6497-6509.