MnSOD, Carotenoids & Prostate Cancer – “You are what you eat” depends on who you are.

When you type Cancer Food Prevention in Google you get about 9 million hits, many of them dotcom sites telling you which nutrients, pills or extracts you should take to prevent cancer. Much of this information is unreliable at least.

Although it is true that numerous observational studies (cohort and case-control) do indicate a relationship between diet and cancer incidence, it is difficult to pinpoint the exact nutrients that may be responsible for a beneficial effect. Furthermore, as explained in “The Best Study Design for Dummies” observational studies provide weaker empirical evidence than RCT’s (randomized controlled trials).

For prostate cancer observational (and preclinical) data indicate that diets high in cruciferous vegetables, soy lecithins and other phytoestrogens, vitamins E and C, lycopene, Selenium, green tea (to name a few) are associated with a lower risk of prostate cancer [1].

However, recent randomized trials did not confirm positive effects of vitamin E and C and Selenium (see previous post on the negative SELECT and the PHS II-trial) and data from the PLCO (Prostate, Lung, Colorectal, Ovarian) Trial [2] suggest that the benefit of lycopene (a powerful anti-oxidant that gives tomatoes their red color) is small and that beta-carotene, an antioxidant related to lycopene, even increases the risk for aggressive prostate cancer.

There may be many reasons why these results discords with the many observational studies performed (3)

• Earlier positive observational studies have less methodological rigor than (large) RCT’s. In controlled trials, the random assignment of subjects to the intervention eliminates the problems of dietary recall and controls the effects of confounding factors.
• RCT’s test one or two nutrients in isolation and sometimes in high doses assuming that a single compound may reproduce the beneficial effects of the whole foods.
• RCT’s are often not stratisfied, differences between individuals are often not taken into account.

That this may be important is shown in a recent study on the manganese superoxide dismutase (MnSOD) polymorfism, prostate cancer and lycopene (4)

The manganese superoxide dismutase (MnSOD) gene encodes an antioxidant enzyme (SOD2) that may protect cells from oxidative damage (which may play an important role in prostatic carcinogenesis). A polymorphism [valine (V) -> alanine (A)] of MnSOD has been recently associated with a higher risk of prostate cancer.

The present study performed by Mikhak et al was a nested case-control study in the Health Professionals Follow-up Study (HPFS) with 612 incident prostate cancer cases and 612 matched controls.

The study not only investigates the role of the MnSOD gene Ala16Val polymorphism in prostate cancer risk, but also measures its interactions with baseline plasma carotenoid concentrations.

In line with several other studies (5), no overall association between MnSOD polymorphism and prostate cancer risk was found. However, a 3-fold [95% confidence interval: 1.37-7.02] increased risk of aggressive prostate cancer was observed among men with the Ala/Ala genotype in the presence of low long-term lycopene status (P-value, test for interaction = 0.02) as compared with men with the Ala/Val+Val/Val genotypes with low long-term lycopene status. In other words when the lycopene blood level is low, the Ala/Ala genotype confers a higher risk of aggressive prostate cancer compared with individuals with the other genotypes.

These results are consistent with findings from an earlier study (6) that reported when total antioxidant status is low, the MnSOD Ala/Ala genotype may be associated with an increased risk of aggressive prostate cancer. In contrast, men with the Val allele were much less sensitive for prediagnostic plasma levels of the anti-oxidants selenium, lycopene and {alpha}-tocopherol.

Thus reasoned the other way around: the anticancer effects of supplemented lycopene and other anti-oxidants may depend on the the MnSOD genotype and the levels of both endogenous and exogenous antioxidants. Similarly, a positive effect of {alpha}-tocopherol (vitamin E) observed in earlier trials appeared to be limited to smokers and/or people with low basal levels of vitamin E (see previous post).

SOURCES

1. E-medicine/Medscape: prostate cancer and nutrition (2008) (free e-txt)
   
2. Peters U, Leitzmann MF, Chatterjee N, Wang Y, Albanes D, Gelmann EP, Friesen MD, Riboli E, Hayes RB. Serum lycopene, other carotenoids, and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):962-8. (free PDF)
   
3. Byers T. What can randomized controlled trials tell us about nutrition and cancer prevention? CA Cancer J Clin. 1999 Nov-Dec;49(6):353-61. Review (free PDF)
   
4. B. Mikhak, D. J. Hunter, D. Spiegelman, E. A. Platz, K. Wu, J. W. Erdman, E. Giovannucci (2008). Manganese superoxide dismutase (MnSOD) gene polymorphism, interactions with carotenoid levels and prostate cancer risk Carcinogenesis, 29 (12), 2335-2340 DOI: 10.1093/carcin/bgn212
5. Bag A, Bag N. Target sequence polymorphism of human manganese superoxide dismutase gene and its association with cancer risk: a review.
   Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3298-305. Review. (Abstract)
6. Li H, Kantoff PW, Giovannucci E, Leitzmann MF, Gaziano JM, Stampfer MJ, Ma J. Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer.Cancer Res. 2005 Mar 15;65(6):2498-504.

You may also want to read:

• The best study design for dummies (2008/08/25/)
• Huge disappointment: Selenium and Vitamin E fail to Prevent Prostate Cancer.(post on this blog about the SELECT trial – 2008/11/16)
• Yet another negative trial with vitamins in prostate cancer vitamins c and e (2008/12/15)

Photo Credits

• http://commons.wikimedia.org/wiki/File:Tomaten_im_Supermarktregal.jpg
• http://commons.wikimedia.org/wiki/File:Lycopene_in_DCM.jpg