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Providing perspectives on recent research into vitamins and nutritionals


Colon Cancer Risk Reduction from Antioxidant Nutrients May Not Be Caused By Antioxidant Activity

By Julia Bird

Greater intakes of certain nutrients with anti-oxidative properties seem to be associated with reduced risk of many cancers. This is thought to be because antioxidants prevent oxidative damage to cells and the resulting DNA mutations that may give rise to cancer. However, antioxidant nutrients can have other effects on the immune system, gene expression and DNA repair in addition to antioxidant activity that could also affect cancer risk.

The subject of interest today is publication by Leenders et al. on the link between antioxidant nutrients and colorectal cancer. The authors used data from the very extensive EPIC cohort, located in various European countries and involving hundreds of thousands of participants, to investigate the link between dietary intakes and blood levels of some carotenoids and vitamins A, C, and E with colorectal cancer incidence in a nested case-control study. The authors identified around 1400 older adult subjects that received a colorectal cancer diagnosis during the study period of 13 years, and matched them to a similar number of control subjects without a cancer diagnosis. They compared blood levels of the 7 most widely consumed carotenoids, vitamin A (retinol), vitamin C, and vitamin E (alpha-, beta-, gamma- and delta-tocopherols), and dietary intakes of beta-carotene, retinol, vitamin C and vitamin E between the case and control groups. In addition, the authors used Reactive Oxygen Metabolite (ROM) levels measured in a subset of the subjects to see whether individuals’ antioxidant status affected the results.

The authors found that plasma retinol levels were inversely associated with lower risk of colorectal cancer, particularly for proximal colon cancer. Higher dietary intakes of vitamins C, E and beta-carotene were also associated with a lower risk of colon cancer. The authors also looked at various sub-groups and found that obese subjects with higher lutein levels had a lower risk of cancer, and higher plasma vitamin C levels reduced risk of colon cancer in overweight and obese subjects. Including the ROM levels of subjects slightly attenuated the results but did not change them significantly.

This study adds to others showing that dietary or serum levels of these nutrients reduce risk of colon cancer. For example, Xu and co-workers found intakes of vitamin C and beta-carotene reduced colon cancer risk in a meta-analysis. Jung and associates found intakes of carotenoids reduced colon cancer risk. A lower risk of colon cancer was found in women who had continually high levels of beta-carotene (Kabat and colleagues).

The lack of effect of antioxidant status is a new finding. Whereas the authors only used a single measurement in a small proportion of the population, therefore the results could be questionable, there are reasons other than antioxidant activity why these nutrients could affect cancer risk. For example, retinol is obtained from the diet either through pre-formed retinol or is produced from beta-carotene via a specialized enzyme in the intestines. Retinol is essential for the immune system, in particular in barrier cells in places like the intestines, and also modulates gene expression. For example, Eisinger and colleagues report that retinol is involved in modulating genes involved in the initiation of cancer. This study does not answer why higher levels of retinol, or greater intakes of vitamins C, E and beta-carotene protect against colon cancer, however they highlight the importance of adequate intakes of all essential nutrients.  


Main reference:

Leenders M1, Leufkens AM, Siersema PD, van Duijnhoven FJ, Vrieling A, Hulshof PJ, van Gils CH, Overvad K, Roswall N, Kyrø C, Boutron-Ruault MC, Fagerhazzi G, Cadeau C, Kühn T, Johnson T, Boeing H, Aleksandrova K, Trichopoulou A, Klinaki E, Androulidaki A, Palli D, Grioni S, Sacerdote C, Tumino R, Panico S, Bakker MF, Skeie G, Weiderpass E, Jakszyn P, Barricarte A, Huerta JM, Molina-Montes E, Argüelles M, Johansson I, Ljuslinder I, Key TJ, Bradbury KE, Khaw KT, Wareham NJ, Ferrari P, Duarte-Salles T, Jenab M, Gunter MJ, Vergnaud AC, Wark PA, Bueno-de-Mesquita HB. Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the european prospective investigation into cancer and nutrition. Int J Cancer. 2014 Apr 26. doi: 10.1002/ijc.28938.

Supporting references:

Eisinger AL, Nadauld LD, Shelton DN, Peterson PW, Phelps RA, Chidester S, Stafforini DM, Prescott SM, Jones DA. The adenomatous polyposis coli tumor suppressor gene regulates expression of cyclooxygenase-2 by a mechanism that involves retinoic acid. J Biol Chem. 2006 Jul 21;281(29):20474-82. Epub 2006 May 14.

Jung S, Wu K, Giovannucci E, Spiegelman D, Willett WC, Smith-Warner SA. Carotenoid intake and risk of colorectal adenomas in a cohort of male health professionals. Cancer Causes Control. 2013 Apr;24(4):705-17. doi: 10.1007/s10552-013-0151-y. Epub 2013 Feb 1.

Kabat GC, Kim MY, Sarto GE, Shikany JM, Rohan TE. Repeated measurements of serum carotenoid, retinol and tocopherol levels in relation to colorectal cancer risk in the Women's Health Initiative. Eur J Clin Nutr. 2012 May;66(5):549-54. doi: 10.1038/ejcn.2011.207. Epub 2011 Dec 14.

Mondul AM, Yu K, Wheeler W, Zhang H, Weinstein SJ, Major JM, Cornelis MC, Männistö S, Hazra A, Hsing AW, Jacobs KB, Eliassen H, Tanaka T, Reding DJ, Hendrickson S, Ferrucci L, Virtamo J, Hunter DJ, Chanock SJ, Kraft P, Albanes D. Genome-wide association study of circulating retinol levels. Hum Mol Genet. 2011 Dec 1;20(23):4724-31. doi: 10.1093/hmg/ddr387. Epub 2011 Aug 30.

Xu X, Yu E, Liu L, Zhang W, Wei X, Gao X, Song N, Fu C. Dietary intake of vitamins A, C, and E and the risk of colorectal adenoma: a meta-analysis of observational studies. Eur J Cancer Prev. 2013 Nov;22(6):529-39. doi: 10.1097/CEJ.0b013e328364f1eb.